POPULARITY
Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Imlunestrant with or without abemaciclib in advanced breast cancer: Results of the Phase III EMBER-3 trial (0:00) Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the Phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1 and PTEN in HR-positive, HER2-negative metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice (7:00) Bhave MA et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat 2024;207(3):599-609. Abstract Camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), versus fulvestrant for postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomized, Phase II trial (10:25) Oliveira M et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol 2024;25(11):1424-39. Abstract Latest on SERDs: An education session at San Antonio Breast Cancer Symposium 2024 (13:57) Jeselsohn RM. Latest on selective estrogen receptor degraders (SERDs). San Antonio Breast Cancer Symposium 2024;Education Session 5. CME information and select publications
The approach to ESR1 and PIK3CA mutations in patients with hormone receptor–positive metastatic breast cancer continues to evolve. What role does circulating tumor DNA (ctDNA) play in treatment decisions? How should oncologists best approach patients with PIK3CA mutations who subsequently develop ESR1 mutations? VK Gadi, MD, PhD, professor and director of medical oncology and deputy director of the University of Illinois Cancer Center in Chicago, discusses with Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair in Hematology-Oncology, how recent data are informing care for patients with comutations. “We now have at least one ESR1-targeting drug out there, and more to come,” Dr. Gadi explains. “Elacestrant is the drug I'm of course referencing, and that is used essentially like a single agent and works well for those patients. Even when they have, for example, PIK3CA mutations present.” He and Dr. Figlin consider when to act on ctDNA findings and potential future strategies. Dr. Gadi reported no relevant financial relationships. Dr. Figlin reported various financial relationships.
Featuring an interview with Dr Sara A Hurvitz, including the following topics: Role of endocrine therapy in the management of HER2-positive breast cancer; implications of the Phase III PATINA study (0:00) Case: A woman in her mid 60s with node-negative, HR-positive, HER2-negative localized breast cancer and a Recurrence Score® of 28 (8:38) Available data guiding the selection of an adjuvant CDK4/6 inhibitor (12:49) Selection of a CDK4/6 inhibitor in the metastatic setting (23:16) Available therapies for patients with HR-positive metastatic breast cancer (mBC) and PIK3CA mutations; implications of the Phase III INAVO120 study (29:17) Case: A woman in her early 60s with HR-positive, HER2-negative mBC with short duration of benefit from a first-line CDK4/6 inhibitor and an aromatase inhibitor (AI) and coexisting PIK3CA and ESR1 mutations (37:11) Available data with approved and investigational oral SERDs (selective estrogen receptor degraders) (43:23) Case: A woman in her early 70s with HR-positive, HER2-negative mBC and an ESR1 mutation detected on disease progression after durable responses to first-line endocrine therapy and second-line CDK4/6 inhibitor with an AI (51:38) Selection of therapy for patients with HR-positive mBC and coexisting targetable genetic mutations (53:11) Case: A woman in her late 50s with HR-positive, HER2-negative mBC and an ESR1 mutation detected on disease progression after first-line CDK4/6 inhibitor with an AI (1:00:17) CME information and select publications
Send us a textWelcome to The Oncology Journal Club Podcast Series 3! Proudly produced by The Oncology NetworkThree respected oncologists dive deep into the most significant research presented at ASCO GI 2025, bringing you practice-changing insights amidst a backdrop of political uncertainty affecting medical research.Professor Chris Karapetis joins hosts Professor Craig Underhill and Professor Christopher Jackson to unpack ground-breaking colorectal cancer studies that are reshaping treatment paradigms. The conversation explores how targeted therapies are dramatically improving survival rates, with the DEEPER study demonstrating cetuximab's superiority over bevacizumab for left-sided RAS wild-type disease, achieving an impressive 50-month median survival when combined with chemotherapy.The experts dissect the BREAKWATER trial, which shows promising benefits of combining encorafenib and cetuximab with chemotherapy for notoriously aggressive BRAF-mutant colorectal cancer. This combination achieved a 61% response rate versus 40% with standard care, with responses lasting significantly longer – representing a potential new standard of care for this difficult-to-treat subgroup.Perhaps most surprisingly, our panel discusses how an inexpensive, familiar medication – aspirin – could reduce colorectal cancer recurrence by 40% in patients with PIK3CA mutations according to the ALASCCA study. This finding highlights how molecular profiling is becoming essential across treatment stages, not just for expensive targeted therapies but also for optimising use of accessible interventions.The discussion extends to exciting developments in pancreatic cancer with a novel pan-RAS inhibitor showing meaningful activity, and advancements in immunotherapy for MSI-high colorectal cancer, confirming combination therapy's superiority. For gastrointestinal oncologists navigating an increasingly complex treatment landscape, this episode offers crucial insights to optimise patient outcomes through precise, personalised approaches.Subscribe to The Oncology Newsletter for regular updates on the latest cancer research and join our community at oncologynetwork.com.au.The Oncology Podcast - An Australian Oncology Perspective
Dr Kaklamani discusses the mechanism of action of inavolisib, the importance of the addition of this agent to the HR-positive metastatic breast cancer treatment paradigm, and considerations for early biomarker testing in patients with breast cancer.
Breast cancer treatment today is becoming more personalized and more precise. Precision medicine is rapidly expanding the options patients have for treating their cancer while helping them maintain a desired quality of life. A common mutation in breast cancer called PIK3CA affects more than 1 in 3 people with breast cancer, making it harder to treat. This mutation often leads to worse outcomes for these patients compared to others. Scientists are now developing new treatments that target this mutation specifically, aiming to reduce side effects and improve treatment outcomes, such as shrinking tumors or preventing disease progression. Today, we are speaking with Dr. Sarah Sammons of Dana-Farber Cancer Institute to explore the exciting new possibilities brought by personalized medicine, including whether it can help slow disease progression and how it can it improve patients' abilities to potentially live more active and productive lives while on treatment.
In today's episode, supported by Genentech, we had the pleasure of speaking with Komal Jhaveri, MD, FACP, about the clinical use of inavolisib (Itovebi) for patients with hormone receptor (HR)–positive, PIK3CA-mutated, locally advanced or metastatic breast cancer. Dr Jhaveri is section head of the Endocrine Therapy Research Program, clinical director of the Early Drug Development Service, and the Patricia and James Cayne Chair for Junior Faculty at Memorial Sloan Kettering Cancer Center in New York, New York. In our exclusive interview, Dr Jhaveri discussed the importance of having a PI3K inhibitor available for the treatment of patients with HR-positive metastatic breast cancer, advice for managing inavolisib-related adverse effects, and best practices for early biomarker testing in patients with breast cancer.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.
BUFFALO, NY - January 22, 2025 – A new #review was #published in Oncotarget's Volume 16 on January 20, 2025, titled “Evolving concepts in HER2-low breast cancer: Genomic insights, definitions, and treatment paradigms." Researchers Whitney L. Hensing, Emily L. Podany, James J. Sears, Shaili Tapiavala, and Andrew A. Davis from the University of Missouri-KC School of Medicine and Washington University in St. Louis School of Medicine explore HER2-low breast cancer, a recently recognized type of breast cancer that is changing the way clinicians should approach treatment. The review explains what makes HER2-low breast cancer different and highlights new treatment options that are helping patients. “Breast cancer, which has been historically classified as HER2-positive versus HER2-negative, is currently facing a paradigm shift in both the definition of HER2 status and in the existing treatment algorithms.” Breast cancer is usually classified into two main types based on the HER2 protein: HER2-positive or HER2-negative. HER2-low breast cancer falls somewhere in between. Thanks to new targeted treatments, such as a drug called trastuzumab deruxtecan, patients with HER2-low breast cancer now have more options and better chances of responding to treatment. The review looks at recent studies on the genetics of HER2-low breast cancer. Researchers found that these tumors are often hormone receptor (HR)-positive, meaning they respond to hormones like estrogen. Some tumors also carry a common genetic change called a PIK3CA mutation, which could affect how well treatments work. However, experts say HER2-low breast cancer is not a completely separate breast cancer type but rather an opportunity for more personalized treatment. “Despite evidence from existing literature that HER2-low breast cancer does not represent a distinct biologic and prognostic subtype, the introduction of HER2-low expression as a therapeutic target has expanded patient eligibility for a potent class of anti-HER2 drugs, HER2-directed ADCs, with potential for significant efficacy.” Despite these advances, diagnosing HER2-low breast cancer can still be difficult. Current testing methods are not always accurate, and different laboratories may get different results. The review calls for better detection methods to make sure patients who can benefit from these new treatments are correctly identified. With cancer treatments becoming more personalized, the review also explains how clinicians can fit HER2-low treatments into existing guidelines to help patients. The success of targeted therapies is changing how breast cancer is treated, especially for patients whose cancer has metastasized. In conclusion, experts believe ongoing research will continue to improve the way HER2-low breast cancer is diagnosed and treated. However, they stress the need for better detection methods and continued exploration of new therapies to help patients get the best possible care. DOI - https://doi.org/10.18632/oncotarget.28680 Correspondence to - Andrew A. Davis - aadavis@wustl.edu About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM
In this JCO Article Insights episode, Giselle de Souza Carvalho provides a summary on "Navigating Treatment Pathways in Metastatic Hormone Receptor–Positive, HER2-Negative Breast Cancer: Optimizing Second-Line Endocrine and Targeted Therapies" by Bhardwarj, et al and "US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Locally Advanced or Metastatic Breast Cancer With PIK3CA/AKT1/PTEN Alterations" by Dilawari et al published in the Journal of Clinical Oncology. TRANSCRIPT Giselle Carvalho: Hello and welcome to JCO Article Insights episode for the December issue of the Journal of Clinical Oncology. I'm your host Giselle Carvalho, Medical Oncologist in Brazil focusing on breast cancer and melanoma skin cancers and one of the ASCO Editorial Fellows at JCO this year. Today, I will be discussing two articles. The first one is “Navigating Treatment Pathways in Metastatic Hormone Receptor–Positive, HER2-Negative Breast Cancer: Optimizing Second-Line Endocrine and Targeted Therapies,” and the second one is the “US FDA Approval Summary on Capivasertib with Fulvestrant for HR-positive HER2-negative Locally Advanced or Metastatic Breast Cancer with PIK3CA/AKT1/PTEN Alteration.” As we know, 65% to 70% of all breast cancers are HR-positive HER2-negative and this is also the most common subtype of metastatic breast cancer. The current standard of care for frontline therapy of patients with luminal metastatic disease is a CDK4/6 inhibitor in combination with endocrine therapy. However, as new endocrine and targeted therapies gain approval, choosing the best systemic therapy upon disease progression after frontline therapy is a topic of ongoing debate. Nearly 40 to 50% of HR-positive breast cancers have actionable genomic alterations and molecular testing should be a routine recommendation for patients with metastatic HR-positive HER2-negative disease. This can be performed repeating tissue biopsy at the time of progression or from archival tissue. Treatment options after progression on CDK4/6 inhibitors include alpelisib in combination with fulvestrant in patients with PIK3CA mutant tumors as seen in the SOLAR-1 trial, or capivasertib with fulvestrant in patients with a tumor mutation in (PI3K)–AKT–PTEN pathway as seen in the CAPItello-291 study, which will be discussed further. In approximately 30% of patients, progression on frontline endocrine plus CDK4/6 inhibitor treatment is caused by endocrine resistance, frequently involving activating mutations in ESR1. For those tumors, elacestrant, an oral SERD is an option as demonstrated in the EMERALD trial. For patients with a BRCA mutation, PARP inhibitors represent another option. If no mutations are detected, everolimus, an mTOR inhibitor, can be used based on the BOLERO-2 results. The phase 2 MAINTAIN and PACE trials, along with the phase 3 postMONARCH trial support changing the endocrine therapy backbone with or without switching the CDK4/6 inhibitor. In less resourced areas, fulvestrant monotherapy is still an option to delay cytotoxic chemotherapy, though its efficacy is limited when used as a single agent. Finally, after progression on at least one line of chemotherapy, antibody drug conjugates including sacituzumab govitecan or trastuzumab deruxtecan may be an option. Now focusing on the PI3K AKT PTEN signaling pathway, activating mutations in PIK3CA and AKT1 and inactivating alterations in PTEN occur in approximately half of luminal breast cancers. In June 2023, the CAPItello-291 trial was published and treatment with fulvestrant plus capivasertib, a PTEN AKT inhibitor, demonstrated a 3.6 month PFS benefit compared to fulvestrant alone, regardless of the presence of AKT pathway alterations. However, for those with tumors without AKT pathway alteration, an exploratory analysis showed that although there was a numerical improvement in PFS, it did not meet statistical significance, indicating that the biomarker positive population primarily drove the positive results noted in the overall population. Therefore, capivasertib plus fulvestrant was approved by the US FDA in November 2023 exclusively for patients with PI3K/AKT1/PTEN tumor alterations after progression on an aromatized inhibitor with or without a CDK4/6 inhibitor. The approved schedule of capivasertib is slightly different from that of other agents used in breast cancer. It is 400 milligrams taken orally twice a day for four days per week every week in a 28-day cycle in combination with fulvestrant. Diarrhea, rash and hyperglycemia were the most commonly reported grade three or four adverse events in the interventional group. I would like to highlight that even though the CAPItello trial excluded patients with glycosylated hemoglobin levels higher than 8% or those diagnosed with diabetes who required insulin, hyperglycemia occurred in 19% of biomarker positive patients treated with capivasertib, with nearly 2% of this population experiencing grade 3 or 4 hyperglycemia and some patients experiencing life threatening outcomes such as diabetic ketoacidosis. By way of comparison, hyperglycemia of any grade was three times higher with alpelisib therapy in the SOLAR-1 trial, occurring in 64% of the patients and grade three or higher hyperglycemia was seen in 37% of the patients. Diarrhea was the most common treatment related adverse event experienced by 77% of the biomarker positive population. Prompt use of the antidiarrheal drugs when needed, such as loperamide must be encouraged as untreated diarrhea can lead to dehydration and renal injury. Cutaneous rash occurred in 56% of the biomarker positive population in the interventional group and 15% experienced a grade 3 or 4 rash. Nearly half of the patients with cutaneous adverse reactions required treatment and this was the leading reason for dose reduction of capivasertib. In the biomarker positive population, the improvement in medium PFS were 4.3 months by investigator assessment. Overall survival data from the CAPItello-291 trial is still immature, but quality of life data was recently published in September this year and was assessed by the 30 item QLQ C30 questionnaire and the QLQ BR23, the breast module. According to Oliveira et al, global health status and quality of life were maintained for a longer period with capivasertib fulvestrant than with placebo fulvestrant except for symptoms of diarrhea which were significantly worse in the capivasertib group. The median time of deterioration of global health status and quality of life was twice as long in the capivasertib group being almost 25 months versus 12 months in the placebo fulvestrant group. These data reinforced the use of capivasertib in combination with fulvestrant for the treatment of HR-positive HER2-negative advanced breast cancer patients with PIK3CA/AKT1/PTEN tumor alterations who have progressed after an aromatase inhibitor-based therapy with or without a CDK4/6 inhibitor. Thank you for listening to JCO Article Insights. This is Giselle Carvalho. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. See you next time. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.
Recent advances in hormone receptor–positive, HER2-negative metastatic breast cancer have led to questions about the timing of genetic testing and the optimal treatment choices for patients. “I, like many others, have changed my personal practice,” says Azka Ali, MD, a medical oncologist at the Cleveland Clinic Taussig Cancer Institute in Ohio. She and Robert A. Figlin, MD, the Steven Spielberg Family Chair in Hematology-Oncology at the Cedars-Sinai Cancer Center in Los Angeles, discuss what newly approved medications for patients with PIK3CA mutations mean for oncologists. “I think the breast cancer landscape is changing faster than we can all keep up with it,” Dr. Ali explains. She breaks down current genetic testing concerns and how she approaches treatment decisions that sometimes take place in a “data-free zone.” Dr. Ali reported no relevant financial disclosures. Dr. Figlin reported various financial relationships.
Welcome to another episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain dive deep into the recent FDA approval of Inavolisib for metastatic hormone receptor-positive breast cancer, based on the groundbreaking INAVO120 study. Join us as we chat with Dr. Komal Jhaveri, a medical oncologist and senior author of the study from Memorial Sloan Kettering Cancer Center. We explored the study design, key findings, and the implications of this new treatment option for patients with PIK3CA mutations. Key topics discussed include: • Overview of the INAVO120 study and its significance • The unique patient population targeted in the study • Key findings, including the impressive improvement in progression-free survival (PFS) • Side effects and management strategies for patients • The importance of genetic testing in treatment decisions Whether you're a healthcare professional or someone interested in the latest advancements in oncology, this episode provides valuable insights into the evolving landscape of breast cancer treatment. Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers! #OncologyBrothers #BreastCancer #ENAVOLacib #PIK3CA #CancerResearch #MedicalPodcast #Oncology Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com
A new PIK3Ca inhibitor is approved for breast cancer.
Join us for an informative discussion about PIK3CA testing and treatment with Dr. Neil Iyengar
Dr Jhaveri discusses the INAVO120 trial of inavolisib plus palbociclib and fulvestrant in PIK3CA-mutant, HR-positive metastatic breast cancer.
El Dr. Juan Carlos Samamé Pérez-Vargas, oncólogo médico, vicepresidente de LABCA, adscrito a la Clínica San Felipe y Hospital Loayza en Lima, Perú, en conjunto con el Dr. William Mantilla, hemato-oncólogo, jefe de la Unidad Funcional de Cáncer de Mama en la Fundación CTIC en Bogotá, Colombia, nos comentan sobre lo más destacado en cáncer de mama presentado en el Congreso de ASCO 2024, resaltando los siguientes estudios: Enfermedad temprana NATALEE: estudio fase III, multicéntrico, aleatorizado, abierto, que evaluó la eficacia y seguridad de ribociclib con terapia endocrina como tratamiento adyuvante en pacientes con cáncer de mama temprano RH+/HER2- y ganglios negativos. Análisis de NCBD: evaluación de la eficacia de la terapia endocrina neoadyuvante en cáncer de mama HER2 bajo frente a HER2-. La respuesta de los pacientes a la terapia incluyó respuesta patológica completa, respuesta patológica parcial, respuesta patológica estable o progresión en el tumor primario al momento de la resección. FLEX: asociación del índice MammaPrint y el resultado a 3 años de pacientes con cáncer de mama en etapa temprana RH+/HER2- tratados con quimioterapia con o sin antraciclinas. RxPONDER: estudio que evaluó la correlación de los niveles de hormona antimülleriana en la identificación de pacientes premenopáusicas con cáncer de mama RH+/HER2- con ganglios positivos, con probabilidad de beneficio de la quimioterapia adyuvante. Enfermedad avanzada postMONARCH: estudio fase III, aleatorizado, doble ciego, controlado con placebo que comparó la eficacia de abemaciclib más fulvestrant vs. placebo más fulvestrant en pacientes con cáncer de mama avanzado/metastásico RH+/HER2-, tras la progresión a un tratamiento previo con un inhibidor de CDK 4/6 y terapia endocrina. INAVO120: estudio fase III, aleatorizado, doble ciego, controlado con placebo que evaluó la eficacia y seguridad de inavolisib más palbociclib más fulvestrant vs. placebo más palbociclib más fulvestrant en pacientes con cáncer de mama localmente avanzado o metastásico, con mutación de PIK3CA, RH+/HER2-. SACI-IO HR+: estudio fase II, aleatorizado, que evaluó el uso de sacituzumab govitecán con o sin pembrolizumab en pacientes con cáncer de mama metastásico RH+/HER2-. DESTINY-Breast06: estudio fase III, aleatorizado, multicéntrico, abierto de trastuzumab deruxtecán vs. quimioterapia a elección del investigador en pacientes con cáncer de mama HER2-bajo RH+, cuya enfermedad ha progresado durante la terapia endocrina en el entorno metastásico. EMERALD: estudio fase III, abierto, multicéntrico, aleatorizado, que comparó la terapia combinada de mesilato de eribulina más pertuzumab más trastuzumab con paclitaxel o docetaxel más pertuzumab más trastuzumab, como tratamiento de primera línea en pacientes con cáncer de mama HER2+ localmente avanzado/metastásico. OptiTROP-Breast01: estudio fase III, aleatorizado, donde se comparó el uso de sacituzumab tirumotecán con la elección de quimioterapia del médico en pacientes con cáncer de mama triple negativo localmente recurrente o metastásico que habían recibido dos o más terapias previas, incluyendo al menos una para el contexto metastásico. Fecha de grabación: 10 de junio de 2024. Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.
Dr. Allison Zibelli and Dr. Megan Kruse discuss the potential benefit of endocrine therapy in ER-low breast cancer; the efficacy and tolerability of triplet therapy in PIK3CA-mutated, HER2-negative locally advanced or metastatic breast cancer; and more key research that will be featured at the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Allison Zibelli: Hello, I'm Dr. Allison Zibelli, your guest host of the ASCO Daily News Podcast today. I am an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Cancer Center of Jefferson Health in Philadelphia. My guest today is Dr. Megan Kruse, a breast medical oncologist and director of breast cancer research at the Cleveland Clinic Taussig Cancer Institute. We'll be discussing key abstracts in breast cancer that will be featured at the 2024 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod. Megan, it's great to have you back on the podcast. Dr. Megan Kruse: Thanks, Alison. Happy to be here. Dr. Allison Zibelli: So, let's begin with Abstract 505. This was another analysis of the SWOG S1007 (RxPONDER) trial, which was the trial that was looking at premenopausal women with intermediate risk oncotype scores. And do they benefit from chemotherapy? If you analyze the whole group, they do benefit from chemotherapy, but what this study questions is whether we can pull out the subset of these patients that actually benefit from chemotherapy? And what they tried doing was measuring various endocrine reproductive hormones and found that anti-mullerian hormone over 10 was the only one that predicted for chemotherapy benefit. What are your key takeaways from this study? Will it help us figure out who is truly postmenopausal biochemically? Dr. Megan Kruse: I think this is really promising. This is one of the toughest situations in clinic, honestly, when you have a premenopausal woman who has an intermediate oncotype risk. We know that chemotherapy is not going to make a huge difference potentially in their breast cancer outcomes, but it may add to some small differential benefit. I think that many of our patients are really afraid about leaving any impactful therapy on the table. And so, it'd be nice to have another marker to help sort out who in this group will really benefit. And the AMH levels, I think, are something that are very accessible for most practices, easily orderable. And it seems like this cutoff of 10 is a very well-known cut point in the AMH interpretation, and a pretty clear-cut point. So, I think it gives a little bit more objective view of who may actually benefit or not. When you look at the results shown in this abstract, for the women in the recurrence score less than 25 receiving chemotherapy followed by endocrine therapy, they had a benefit in five-year invasive disease-free survival of 7.8%. When you look at those oncotype reports and they suggest how much benefit you might get, that's right around the same number you see. So, I think that's supporting that this is the subgroup that's benefiting. When you look at those patients with AMH less than 10, they actually had a negative 1.7% difference in overall survival. So, you wonder, are we harming these patients by giving them chemotherapy? I think that's too far of a stretch to say. I wouldn't be worried about harm. But hopefully, we can stop giving chemotherapy to patients who truly are not going to benefit if we have an additional biomarker of response. That's what the promise is for this. So again, another potentially actionable abstract that we can put into practice pretty quickly. It's going to be hard to know how to use this, also in the context of the upcoming OFSET study or BR009, which is of course the study in the same group of premenopausal patients with node-negative or 1-3 lymph nodes involved, and intermediate oncotype scores, randomizing them to endocrine therapy with ovarian suppression versus chemoendocrine therapy. It would be kind of nice to see the AMH levels incorporated into that model to see if the same trend holds true. But I think we go back to the TAILORx and RxPONDER studies many times as good quality data, and the trend here is really striking. Dr. Allison Zibelli: I really like this study because one of the things I often struggle with in the clinic as a practicing breast oncologist is who's really in menopause. And we end up having these fights with the gynecologists where sometimes our opinions differ. And it would be really nice to have something this clear cut to say, “You're in biochemical menopause or you're not.” So, I look forward to seeing this used in a lot of different ways in the future. Dr. Megan Kruse: Yeah, I agree. And I think it's based on the other markers we have with estrogen levels, with FSH levels. If you're checking those sequentially in patients, we know they go up and down, and it's really hard to tell what we are capturing at this single point in time. And maybe that's what we're seeing in this analysis is that the AMH is a little bit more stable and reliable marker. So, I really love that. And I don't know about you, but in clinical practice it can be really hard. A lot of our patients have had uterine ablations or hysterectomies but have intact ovaries. And so, figuring out ovarian function status is actually much, much harder than it may seem superficially. Dr. Allison Zibelli: Okay, so let's focus on Abstract 513. I thought this was really interesting. It's a group of patients that we don't have much data for, and that's women that are ER-low, with an ER of 1% to 10% in early-stage breast cancer. Right now, national guidelines are sort of on the fence about whether these women benefit from endocrine therapy. So that's what this study tried to focus on. How will this study change how we approach this group of patients? Dr. Megan Kruse: This study really gave me pause and made me rethink what I'm doing on a day-to-day basis, because here, what the authors found in a very large NCDB analysis was that for women with ER-low status, so ER 1% to 10% positive, they actually did have benefit receiving endocrine therapy, it seems. What they found, after you adjust for many other confounding factors like age, comorbidity, and PR status, is that patients with ER-low breast cancer when they did not receive endocrine therapy actually had worse overall survival outcomes with a hazard ratio of around 1.2 to 1.3. This is a group where I have typically not pushed endocrine therapy very strongly. I think the patients, especially now, are receiving such intense therapy with chemoimmunotherapy in the preoperative setting, by the time they reach their adjuvant phase with immunotherapy, maybe with capecitabine, maybe with a PARP inhibitor, endocrine therapy seems, “Oh, why bother after we've done all of this?” And we know that the toxicities of endocrine therapy are real and can be very problematic. And so, I have often felt like it's the least important part of therapy and questioned whether we should even bother. But I think this analysis really challenges that and makes us think twice. And I think it speaks to a theme that we're seeing more and more about the heterogeneity of these breast cancer subtypes. And again, talking about clear-cut points in analysis, nothing is truly black and white. So maybe that little bit of expression does mean something. It does kind of stand in contrast to what we see in studies of ER-low behaving a bit more triple-negative like, but maybe they're their own category, and maybe it gives us a place to look for other therapy synergy in the future. But it certainly will make me stop and think again when I see a ER 4% patient. Should I talk to them about endocrine therapy? Dr. Allison Zibelli: Yeah, I totally agree with everything you said there. And we know that this is a biologically different group of patients than the ER strongly positive group, but maybe not as different as we once thought. Dr. Megan Kruse: Yeah. And I think there's still a lot of unknowns here about what if they're ER truly negative and PR a little bit positive. So, these clinical situations don't come up that frequently, but when they do, they're humbling, because I think we really, as much data as we have in breast cancer, it's pretty limited for these types of patients. Dr. Allison Zibelli: So, let's move on to Abstract 1003, which was a new combination in the INAVO120 trial. It was palbociclib plus fulvestrant with either inavolisib or placebo in patients with PIK3CA-mutated hormone receptor-positive, HER2-negative, locally advanced metastatic breast cancer in the second line, who relapsed within 12 months of adjuvant endocrine therapy completion. This is a big group of patients for us. Can you tell us about the study? And does this triple therapy, in your mind, represent a new standard of care? Dr. Megan Kruse: Yeah, this study was initially presented at our 2023 San Antonio Breast Cancer Symposium, and there I felt like it was a little bit of a surprise. There's been so much talk about PI3K-AKT-PTEN pathway impactful drugs and targetable mutations. We've heard a lot about alpelisib and capivasertib, and how these drugs are fitting into our practice. Then all of a sudden, we have this data with inavolisib that I wasn't really expecting to see. And perhaps I think one of the reasons that this study came about so suddenly, seemingly, and so quickly is because it looks at a really high-risk patient population. And so, these are those patients that are having relapses of their breast cancer within their initial, while on adjuvant AI therapy or within 12 months of stopping. And so, having a marker of this patient group that is developing, I think, early endocrine resistance and it's another space where it's kind of hard to identify who these patients are upfront. And so their response to therapy tends to be one of the best markers of risk moving forward. So, when this trial was originally presented, what was quite striking is that the progression-free survival was more than doubled for the triplet combination compared to the control arm. And those numbers were PFS of 15 months versus 7.3 months for the triplet versus the control. The response rate was also significantly improved, with the triplet going above 50%, versus a response rate in the control of about 25%. So, the results were really striking. But they clearly come with some caveats, which are that this is a very defined patient population of risk. Of course, they have to have the biomarker of a PIK3CA mutation, and in the control arm here, there was no PIK3-targeted medication. And so you wonder, are we just getting better results by including that more specific targeted therapy earlier on? It's hard to know, but I think that could certainly be a big part of this. And the other caveat, when I'm looking at the data, is how might we think about this in our real population? Because as we know, drugs that impact this pathway tend to have a lot of toxicity concerns, primarily hyperglycemia, diarrhea, and rash. And with this particular agent, there was also notable stomatitis, which is something we've seen with everolimus, of course, in this pathway, but not maybe as much with alpelisib and capivasertib. When you're thinking about all of those toxicities, keep in mind that this trial population included patients with a pretty tight fasting blood sugar requirement, A1c of less than 8, and not requiring insulin. So all of that being said, I think this combination seems really intriguing for efficacy. This is a patient population I'm worried about, because we know that these patients are likely not going to get the same upfront benefit of CDK4/6 inhibitor-based therapy, like maybe we see for a patient with long disease-free survival or de novo metastatic breast cancer. But I think it's going to have some meaningful issues in clinic regarding tolerability. And then, of course, the regimen is more complex. We're talking about two different oral agents and an intramuscular injection, which could be hard for some patients, and it's going to have some decent financial toxicity associated with it. So, I think it's really, really exciting and has the potential to make an impact in first-line therapy. But I don't envision it being the standard of care first-line therapy for everyone, particularly in light of some of the other data we have in the first line questioning, like from the SONIA trial, how important is CDK for everyone? Again, this is I think where we're starting to get subsets within subsets of this first-line patient population of who needs escalation of therapy and who may benefit from more de-intensified therapy. Dr. Allison Zibelli: I agree, these agents have significant toxicity, and especially financial toxicity is something that we at the academic setting frequently forget about because a lot of our patients are on trials. So, it will be interesting to figure out how we're going to use these agents in real life. So, for our final abstract, I wanted to discuss Abstract 10508, which was a prevention trial. I think pretty much everybody's patients are going to be asking them about this because it's about GLP-1 inhibitors. We know that bariatric surgery does prevent obesity-associated cancers. This study explored whether the GLP-1 agonists could offer a similar result to bariatric surgery in patients with BMIs over 35. What do you think about this study? Dr. Megan Kruse: I thought this was such an interesting and timely study and question. These drugs are out there – Ozempic, Mounjaros, and Wegovy – and our patients ask about them. And I think there has been a lot of interest for years now about the impact of lifestyle factors on cancer incidence, particularly in breast cancer, where we know that obesity does seem to be related to cancer incidence. And with all of our concerns about hormonal exposure and extra weight, extra adipose tissue being a source of potential extra estrogen, this is a really key topic. Talking about financial toxicity, again, I think that is honestly probably the bigger hurdle because this study does reinforce that patients who are receiving GLP-1 receptor antagonists and those who have had bariatric surgery do benefit in terms of cancer-related survival and all-cause related survival. So, I think the impact on metabolic factors is making a difference in cancer incidence and outcomes. But access and equity will be the big issue here, right? Dr. Allison Zibelli: Yes. Dr. Megan Kruse: Can we get patients on these drugs? I certainly have had patients with a history of breast cancer who have been on these medications, and they have done great with them in terms of weight loss. We know that our therapies, many times, do have the side effect of weight gain. So, I wonder if there is a part of weight management that maybe we haven't talked about so much as oncologists that we need to talk about moving forward and would be very welcome by our patients. But it'll have its own caveats, of course. Not only the financial issue but there's the durability issue. And I think when you look at the degree of impact of these medications versus bariatric surgery, you do see a greater impact from bariatric surgery, in not only the degree of weight loss but also the sustainability of that weight loss. So, I think for the right patient at the right time, bariatric surgery may still be the better option, but that's not going to be an option for a lot of patients. It is a huge shift in lifestyle and medications and many ways might be easier, so more to come. I also wonder about looking at this data through the lens of different cancer types. What will we find out? Is the trend for colon cancer going to be different from the trend for breast cancer? Will the trend within breast cancer be different for breast cancer subtypes? I would very much welcome more data in this space, and it is nice to see a first step forward. Dr. Allison Zibelli: I thought the most interesting thing about this study was that while bariatric surgery patients lost more weight, GLP-1 patients had a higher decrease in obesity-related cancer risk. So, it shows to me that there is something beyond just weight. It is something in metabolism that is driving these cancers. Dr. Megan Kruse: Yes, and I think that that goes back to some things we have thought about for a long time with insulin levels and insulin-like growth factor, and all of these things that I think when our patients look at more metabolic approaches to cancer control, this is probably what we are trying to get at. We have just never had great ways to measure it or influence it, and perhaps now we finally do. I would love to see some partnering work here in the future with oncologists and endocrinologists and digging into these patients who have great responses to see what we are actually seeing at the hormone level. Dr. Allison Zibelli: Well, thank you so much, Megan, for your great insights today on the ASCO Daily News Podcast. We really appreciate you coming to talk with us again. Dr. Megan Kruse: Thank you. It has been a great conversation. Thank you for opening my eyes to these abstracts, and I am happy to see what else ASCO brings. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find links to all the abstracts we discussed today in the transcript of this episode. Finally, if you value the insights you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. It really helps other people find us. Thank you for listening. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. The guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Allison Zibelli Dr. Megan Kruse @MeganKruseMD Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Allison Zibelli: None Disclosed Dr. Megan Kruse: Consulting or Advisory Role: Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, Lilly
Featuring perspectives from Dr Seth Wander, including the following topics: Case: A woman in her mid-50s with ER-positive, PR-negative, HER2 IHC 1+ metastatic breast cancer (mBC), Recurrence Score® (RS) = 35 (0:00) Mechanisms of resistance to antiestrogen therapy in HR-positive mBC (2:33) Optimal approaches to biomarker assessment (15:37) Case (continued): A woman in her mid-50s with ER-positive, PR-negative, HER2 IHC 1+ mBC, RS = 35 (18:27) Case: A woman in her early 60s with de novo HR-positive, HER2-negative mBC with an ESR1 mutation after disease progression on first-line ribociclib/letrozole (20:22) EMERALD — Phase III data guiding the use of elacestrant (21:39) Emerging oral selective estrogen receptor degraders — camizestrant and imlunestrant (29:32) Case (continued): A woman in her early 60s with de novo HR-positive, HER2-negative mBC with an ESR1 mutation after disease progression on first-line ribociclib/letrozole (45:44) Case: A woman in her early 60s with HR-positive, HER2-negative mBC and a PIK3CA mutation who develops a new ESR1 mutation after disease progression on CDK4/6i and aromatase inhibitor (47:22) CAPItello-291 — Phase III data guiding the use of capivasertib (48:52) Case (continued): A woman in her early 60s with HR-positive, HER2-negative mBC and a PIK3CA mutation who develops a new ESR1 mutation after disease progression on CDK4/6i and aromatase inhibitor (52:41) Additional promising antiestrogens — vepdegestrant and lasofoxifene (58:41) CME information and select publications
Dr. Angela DeMichele, Dr. Lynn Henry, and Dr. Harold Burstein present the latest breast cancer rapid recommendation update impacting two ASCO guidelines. This update focuses on the new option, capivasertib plus fulvestrant, for patients with hormone receptor-positive, HER2-negative metastatic breast cancer with activating PIK3CA or AKT1 mutations or inactivating alterations in PTEN based on data from the recent CAPItello-291 trial. They discuss the updated recommendations on lines of endocrine treatment and selecting between the options for patients with activating PIK3CA mutations. Additionally, we discuss implications for clinicians and patients, and what ongoing research is occurring in the field. Read the latest update, “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer – Capivasertib-Fulvestrant: ASCO Rapid Guideline Update“ at www.asco.org/breast-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00248 Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Harold Burstein from Dana-Farber Cancer Institute, Dr. Angela DeMichele from the University of Pennsylvania, and Dr. Lynn Henry from the University of Michigan, co-chairs on “Endocrine and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Capivasertib–Fulvestrant: ASCO Rapid Guideline Update.” Thank you for being here, Dr. Burstein, Dr. DeMichele, and Dr. Henry. Dr. Harold Burstein: We're happy to be here. Brittany Harvey: And before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including our guests on this episode today, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes. So then, to kick us off, Dr. Burstein, could you first describe what prompted this rapid update, which provides updated recommendations for two ASCO guidelines: the biomarkers for systemic therapy in metastatic breast cancer guideline, and the endocrine treatment and targeted therapy for hormone receptor-positive, HER2-negative metastatic breast cancer guideline? Dr. Harold Burstein: Thanks, Brittany. Well, this team has been working, as you mentioned, actually, on two guidelines, which are clearly evolving in parallel and kind of converging, actually, when you look at data, as we'll be talking about in the next few minutes. The particular catalyst here was a large randomized clinical trial which looked at a new targeted therapy in the space of estrogen receptor-positive, HER2-negative breast cancer. That drug is capivasertib. And the trial was the so-called CAPItello study. In that trial, patients who were receiving second-line therapy with fulvestrant were randomized to that treatment alone, or that plus capivasertib. So the data from that study were the first strong signal that we needed to update the guideline because they were important clinical data. The other strong signal was that the drug was tested in a cohort of patients who had a specific set of mutations in their cancers. And that included PIK3CA mutations, a class of mutations for which we already had a targeted drug. But it also included some new potential targets, including mutations in the AKT gene itself, capivasertib is an AKT inhibitor, as well as loss of PTEN protein functionality, which potentially sensitizes tumors to the targeted action of this drug as well. So while we had a couple of guidelines catching up on the endocrine therapy space, which is increasingly looking like a targeted therapy space, it was clear that this major study, which had clinical and diagnostic implications, would sort of push them together and served as the impetus for updating both guidelines at the same time. Brittany Harvey: Understood. I appreciate that background information. So then, Dr. DeMichele, based on this updated data that Dr. Burstein just described, what is the updated recommendation from the guideline panel regarding lines of endocrine treatment? Dr. Angela DeMichele: Well, I think this is where the biomarker evolution that Dr. Burstein just referred to really comes in because now we have the opportunity to perform genomic testing in patients who have ER-positive, HER2-negative metastatic breast cancer, on either the tumor or commonly from the blood. And we can now start to tailor treatment to the specific genomic abnormalities that that patient's tumor contains. So now our guideline really marries both the genomic abnormality with the therapeutic option. First-line treatment remains endocrine therapy plus a CDK 4/6 inhibitor. But things then really start to diverge once we enter second and third-line therapy because at that point, we now have the option to test for several genomic markers: ESR1 mutations, PIK3CA mutations, AKT1 mutations, and PTEN inactivation. And based on whether the tumor has one or any of those mutations, we can then select the therapy based on that. So in the case of capivasertib, as you just heard, that is a therapy for patients whose tumors have PIK3CA mutations or activating mutations in AKT1 or loss of PTEN. But other patients who don't have one of those mutations may, in the second line, go on to another drug. For example, if they have an ESR1 mutation, they then may be eligible to take elacestrant. Patients who have no targetable mutations still have a targeted option in that they can use everolimus. And in all of these settings, the endocrine therapy partner for this line of therapy is typically fulvestrant. So now we're really starting to tailor therapy in the second- and third-line based on genomic changes. Brittany Harvey: Excellent. That information is helpful for choosing optimal therapy tailored to the individual patients, as you just described. So then, Dr. Henry, what guidance does the expert panel provide regarding choosing a PIK3CA targeted option? Dr. Lynn Henry: Thank you. So for patients whose tumors are found to have an activating mutation in PIK3CA, we now have two drug options: either alpelisib or capivasertib in combination with fulvestrant. And the problem is, these drugs have not been compared head-to-head. We can't say that one is clearly better than the other, either in terms of efficacy or in terms of side effect profile. What we do have is information from two separate trials in which they were each tested against placebo. The efficacy appears to be fairly similar based on the data that we have. It does appear that the side effect profiles may be slightly different. And so, when you have a patient sitting in front of you and you're trying to decide how best to treat her, you really have to think about, what symptoms does my patient already have? What is she more or less likely to tolerate? So what we do know is that it appears that the rates of grade 3 diarrhea and rash were slightly higher with capivasertib. It looks like hyperglycemia was higher with alpelisib, as was treatment discontinuation. So really you have to make an individualized decision when you have a patient sitting in front of you about which drug you'd like to try. Of course, if someone doesn't tolerate one drug, you can always switch to the other one. Brittany Harvey: I appreciate that analysis and to provide guidance without a head-to-head trial and to specifically provide options based on an individual patient's profile. So then, Dr. DeMichele, what should clinicians know as they implement these new recommendations? Dr. Angela DeMichele: Well, first of all, I think most clinicians now are becoming more familiar with the procedures required for doing genomic testing. But this is something that now has become the standard of care. And so, it is incumbent upon all of us who treat these patients to understand what the options for genomic testing are for that patient, which companies offer this testing, how to send a sample, and how to interpret the report that comes back. So, I think this has really added a level of complexity to the therapy for patients. I also think that one can't simply apply an algorithm to a patient. We have to really treat the whole patient and we have to take into consideration, as Dr. Henry said, the toxicities of these agents and the cost which is also a major issue. So I think that while it is more complex, really that doctor-patient relationship is so important in communicating what these genomic tests mean for a patient and for their options, and also important for the clinician to really understand what the different therapeutic agents might mean for a patient, and really try to pick the agent that's best for that patient. Using genomic testing is just one of several different features that they'll consider. Brittany Harvey: Absolutely. It's key to obtain the data needed to select appropriate patients and to recognize the complexity. So then, Dr. Henry, in your view, how will this update impact patients with metastatic breast cancer? Dr. Lynn Henry: Yes, so as we've discussed, I think this is really exciting. Over the last few years, we have had quite a number of new medications that have become available for patients and have been FDA-approved. And so this is yet the latest in a series. For those patients whose tumors have a PIK3CA mutation, as we discussed, there are now two options. So you have a choice depending on which one is better covered by insurance, by which one you may tolerate better. But I think the other thing is now, although it's a smaller subset of patients, there are patients out there whose tumors have mutations in AKT1 or alterations in PTEN, and so there's an entirely new endocrine therapy-based option available for them that wasn't available before. So I think that thinking about the new data that are out there, the new drugs that are out there, really is exciting because there are new options available and hopefully there are more to come as well. Brittany Harvey: Absolutely. It's great to have these new options. So, finally, Dr. Burstein, Dr. Henry just mentioned what's to come. Could you touch on what some of the outstanding questions are regarding endocrine therapy for patients with metastatic breast cancer? Dr. Harold Burstein: A couple of things to say. First, ER-positive metastatic breast cancer is the most common kind of metastatic breast cancer, roughly three quarters of metastatic cases of breast cancer will be hormone receptor-positive cancers. So this is a very big public health issue around the world, actually, breast cancer being the number one most commonly diagnosed cancer of women around the world. So minor or major improvements in treatment for advanced ER-positive breast cancer really have a tremendous impact. The second thing is it's been remarkable to see the progress in the past decade. We've gone from simply targeting the hormonal access itself with medicines like tamoxifen or aromatase inhibitors or an injectable selective estrogen receptor degrader like fulvestrant to incorporating targeted therapies at the same time. And this whole class of drugs called CDK4/6 inhibitors has emerged which we use in either first- or in second-line therapy. Those drugs have transformed our standard of care, improved survival for patients with advanced ER-positive disease, now with median survival nearly 50% longer than what we had seen in the past. And if you've heard, we have a wealth of opportunities. We can target PIK3CA, we can target ESR1 mutations. Other drugs emerging in the space include PROTACs which is another way of degrading the estrogen receptor. And so there's going to be more progress in the years to come. So one of the biggest challenges has been to try and understand, is there really an optimal way to use these drugs, or can we be smarter about the particular sequence of all these particular things that are happening. So one example of this was a recent study that is on a drug, not as yet FDA-approved, called inavolisib, which is a PIK3CA targeted drug used in first line in combination with a CDK4/6 inhibitor and endocrine therapy. And that study, for a high-risk group of women with ER-positive metastatic disease, actually showed a dramatic improvement in overall survival, asking the question if combining some of these targeted therapies together might yet further improve outcomes. And as you've heard from the diagnostic space, one of the other interesting things is that tumors evolve over time. And so acquisition of the estrogen receptor mutations, ESR1 mutations, which are typically not found early in the course of advanced breast cancer but otherwise later, now have targeted treatments. So there's a whole bunch of stuff going on all at the same time, including multiple ways of targeting things, serial testing to look for acquisition of ESR1 mutations and new pathways to explore. It's an embarrassment of riches in some respects because it has meant it's actually really hard to write a guideline as you've heard, which says, “Do this first, do this second, and do this third.” I suppose that's a good problem to have under the circumstances, but it's going to require really thoughtful clinical trials and careful analysis to help guide specific lines of treatment recommendations like that. Brittany Harvey: Excellent. We'll look forward to these exciting, continuing developments for patients with metastatic breast cancer. And I want to thank you all so much for your work to develop this rapid recommendation update for these two guidelines. And thank you for taking the time on this podcast today. Dr. Harold Burstein: Thanks. Dr. Lynn Henry: Thank you so much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experiences, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
In this discussion with Dr. Hope Rugo, we covered her study Capitello-291, which led to the approval of Capivasertib in hormone receptor-positive breast cancer with AKT1, PTEN, and PIK3CA mutations, which are seen in 40-50% of the cases. We touched base on sequencing of this therapy, and important clinical pearls around the side effect management associated with this drug.
This episode features an interview with Carlos Doti, MD, Vice President, US Medical Affairs Oncology, AstraZeneca, about new breast cancer treatments.Dr. Doti is a hematologist by training and is passionate about developing treatments that have a real impact for people living with cancer across every aspect of their disease. Dr. Doti has worked in industry for the last 14 years, including seven years at AstraZeneca in various roles, and in small markets like Argentina as well as larger global markets. Since 2022, Dr. Doti has been focusing on the US market in hematology and oncology, working in breast, lung, GI and gynecological cancers among others.Dr. Doti has previously served in medical affairs roles at Novo Nordisk A/S and Pfizer. His work is supported by more than 70 congress presentations and several peer-reviewed publications. He has also served as an investigator in more than 25 clinical trials in hemostasis, onco-hematology and infectious disease.Recently, AstraZeneca won approval for the company's AKT inhibitor Truqap (capivasertib) in combination with Faslodex (fulvestrant) for the treatment of hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1, or PTEN). The approval of Truqap was the first-in-class approval for AstraZeneca.Tune into the episode to hear more about the milestone approval of the new combination breast cancer treatment, which has been a much-needed treatment option for the nearly 50 percent of patients with advanced HR-positive breast cancer who have PIK3CA and AKT1 mutations or PTEN alterations, and experience resistance to first-line treatments such as endocrine therapies and CDK 4/6 inhibitors. For more life science and medical device content, visit the Xtalks Vitals homepage.Follow Us on Social MediaTwitter: @Xtalks Instagram: @Xtalks Facebook: https://www.facebook.com/Xtalks.Webinars/ LinkedIn: https://www.linkedin.com/company/xtalks-webconferences YouTube: https://www.youtube.com/c/XtalksWebinars/featured
Welcome back to another episode of Breast Cancer Conversations, where we continue to share valuable insights from the San Antonio Breast Cancer Symposium. As a breast cancer survivor and the founder of survivingbreastcancer.org, I'm thrilled to bring you key takeaways from one of the world's largest breast cancer conferences.In this episode, we focus on what to do when CDK4-6 inhibitors, such as Ibrance, Kisqali, and Verzenio, stop working. Our guest, Amy Bremer, highlights the importance of getting a biopsy to check for mutations, which can be done through a liquid biopsy or a tissue biopsy. This step is crucial for determining the next course of action.We delve into the various treatment options available based on specific mutations. For instance, if your cancer has a PIK3CA mutation, a combination of PIQRAY and Faslodex might be recommended. Other drugs like Trucap, Orserdo, and LSS strontosome are also discussed as potential options for different mutations.For those without mutations, there are still choices available, such as Affinitor plus Faslodex, or considering a switch to a different CDK4-6 inhibitor. We also discuss the possibility of continuing treatment beyond progression or, in cases of aggressive progression, looking into chemotherapy or antibody drug conjugates (ADCs).Stay tuned for our next episode, "on SERDs, SERMs, CERANs, and PROTACs" and remember to subscribe to Breast Cancer Conversations. Please note that our podcast shares personal experiences and is not a substitute for professional medical advice. If you have specific topics in mind or want to be a guest, feel free to reach out to me.Thank you for listening, and let's continue to empower each other through community, education, and resources.00:02:44 - Topic: CDK4-6 Inhibitor Efficacy00:03:31 - Options After Endocrine Therapy and CDK4-6 Inhibitors00:04:35 - Treatment Options Based on Specific Mutations00:05:40 - Options Without Identified Mutations00:06:43 - Inherited Mutations and Treatment Choices00:07:09 - Expert Opinions on Treatment Complexity00:08:44 - Importance of Clinical Trials+++++++++++++++++++++Attend a free virtual SurvivingBreastCancer.org event:https://www.survivingbreastcancer.org/eventsFollow us on InstagramLaura and Will: https://www.instagram.com/laura_and_will/SurvivingBreastCancer.org: https://www.survivingbreastcancer.org/Breast Cancer Conversations: https://www.instagram.com/breastcancerconversations/About SurvivingBreastCancer.org: SurvivingBreastCancer.org, Inc. (SBC) is a federally recognized 501(c)(3) non-profit virtual platform headquartered in Boston with a national and global reach. Through education, community, and resources, SurvivingBreastCancer.org supports women and men going through breast cancer. We provide a sanctuary of strength, compassion, and empowerment, where those diagnosed with cancer unite to share their stories, learn invaluable coping strategies to manage wellness and mental health, and find solace in the unbreakable bond that fuels hope, resilience, and the courage to conquer adversity.Support the show
Recently, the FDA granted approval to capivasertib in combination with fulvestrant for patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations. In this interview, Editorial Board member Dr. Jason Mouabbi speaks with Dr. Carlos Doti, Head of Medical Affairs, US Oncology at AstraZeneca, about the significance of the approval, its dosing schedule, AstraZeneca's approach towards patient education and adverse event management, and the future of capivasertib in different treatment settings.
Dr. Banu Arun and Dr. Sana Al Sukhun share recommendations from the newest ASCO resource-stratified guideline on systemic treatment for patients with metastatic breast cancer. They describe the importance of this new guideline, the four-tier resource setting approach, key recommendations, and implementation considerations. Recommendations are discussed for systemic therapy for HER2-positive, triple-negative, and hormone receptor-positive metastatic breast cancer, across Basic, Limited, and Enhanced resource settings. Drs. Arun and Al Sukhun highlight the importance of this guideline for clinicians and patients in regions with limited resources to optimize cancer care. Read the full guideline “Systemic Treatment of Patients with Metastatic Breast Cancer: ASCO Resource-Stratified Guideline” at www.asco.org/resource-stratified-guidelines." TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/resource-stratified-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the JCO Global Oncology, https://ascopubs.org/doi/10.1200/GO.23.00285 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Banu Arun from the University of Texas MD Anderson Cancer Center in Houston, Texas, and Dr. Sana Al Sukhun from Al Hayat Oncology Practice in Amman, Jordan, co-chairs on “Systemic Treatment of Patients with Metastatic Breast Cancer: ASCO Resource-Stratified Guideline.” Thank you for being here, Dr. Arun and Dr. Al Sukhun. Dr. Banu Arun: Thank you for having us. Dr. Sana Al Sukhun: Thank you. Pleasure to join you. Brittany Harvey: And before we discuss this guideline, I'd just like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including the guests who have joined us today on this episode, are available online with the publication of the guideline in the JCO Global Oncology, which is linked in the show notes. Then, to jump into the content of this guideline, Dr. Al Sukhun, can you first provide an overview of the scope and the purpose of this guideline? Dr. Sana Al Sukhun: Sure. And again, thank you, Brittany. Pleasure to join you. This guideline is really interesting and very important. It addresses the care and treatment of the most common cancer worldwide, particularly metastatic breast cancer, taking into consideration different availability of resources, particularly in countries with limited resources. As you know, most of us are aware of the importance of clinical practice guidelines improving outcomes for patients in medicine, not only in oncology, but most of those guidelines are developed in countries that are highly resourced. So their applicability in countries of limited resources that lack infrastructure and resources is definitely limited because they cannot really adopt and adapt to those guidelines, which makes resource adapted or resource stratified guidelines quite important and helpful. First, to clinicians caring for patients so that they can properly allocate resources, prioritize how to use therapy for patients, but also even policymakers to allocate resources and plan graduated implementation of science to improve outcomes for their patients according to the progressive availability of resources. So we're talking about breast cancer, the most common cancer worldwide. And not only is it the most common cancer worldwide, but also more than two-thirds of new cases are diagnosed in countries of limited resources. Unfortunately, they also carry the burden of more than 70% of the mortality attributed to breast cancer. Another challenge is that the median age for the patients affected with breast cancer in countries of limited resources is indeed at least a decade younger than Western societies, which adds to the burden, not only the social, but also the economic burden of cancer. And unfortunately, presentation in these countries is mostly locally advanced, metastatic breast cancer, therefore comes the focus on helping our colleagues in countries of limited resources to care for patients according to the resources available, not only in countries of limited resources, even colleagues practicing in less fortunate areas within countries that are highly resourced. Brittany Harvey: Excellent. Thank you for providing that background information for this guideline. So then you've just described how many countries and areas have different resources. So, Dr. Arun, could you describe the four-tier resource setting approach that this expert panel used? Dr. Banu Arun: Yeah, Brittany, that's a good question. I think it's important to know where we started and what infrastructure we used. So for developing resource stratified guidelines, ASCO has adopted its framework from the four-tier resource setting approach, which was actually developed by the Breast Health Global Initiative, and we employed modifications to that framework based on the disease control priorities. What this framework emphasizes is also that variations can be present not only between countries, but actually within countries with disparities, for example, differences between rural and urban areas within one country. So the four settings are obviously basic, limited, enhanced, and maximal settings. The basic setting includes core resources or fundamental services that are really absolutely necessary for any public health, primary health care system to function at all. These include services that are typically applied in a single clinical interaction. For example, vaccination is feasible for highest need populations. The next tier would be the limited setting. That includes countries or settings with second-tier resources or services that are intended to produce major improvements in outcomes, such as incidences and cost effectiveness. Unlike the basic setting, it can involve single or multiple interactions with providers or healthcare services. Then the third tier is the enhanced setting, where the services are optional but important, and these services should ideally produce further improvements in outcome and increase the number of quality of options and also individual choices, maybe countries having the ability to track patients and links to registries. And then the last one is of course, the maximal setting that includes high-level, state-of-art resources and services that are available in some high-resource countries. Brittany Harvey: Thank you for describing that framework and the approach that the panel used. So then I'd like to move on and talk about the key high-level recommendations of this guideline for systemic therapy for metastatic breast cancer across those three lower tiered resource settings - the basic, limited, and enhanced resource settings. So, Dr. Al Sukhun, could you start with the recommendations across these settings focusing on HER2-positive breast cancer? Dr. Sana Al Sukhun: Sure. You know, HER2-positive metastatic breast cancer is one of the most aggressive subtypes of breast cancer. However, its outcome has been transformed with the introduction of HER2-targeted therapy. So, apart from patients who suffer from congestive heart failure or limited compromised ejection fraction, which can be evaluated on a case-by-case basis, patients are candidates for HER2 targeted therapy. When we made the recommendations according to the availability of resources, we started in a gradual approach. So, in a maximal setting, you treat patients with HER2-positive metastatic breast cancer in the frontline setting using the combination of trastuzumab, pertuzumab, and taxanes or endocrine therapy if patients have limited disease burden, or if they have the recurrence after a long disease-free interval. Usually, the combination of trastuzumab and pertuzumab with taxane is used. But then again, clinicians can use navelbine, considering good data from the HERNATA trial about its efficacy as compared to taxanes and even also, we recommended platinum therapy according to availability. However, if pertuzumab is not available, you go to the next level where we recommend offering, again, chemotherapy, be it taxane, navelbine, platinum, with trastuzumab, or even without trastuzumab if trastuzumab is not available. So, something to keep in mind, chemotherapy is not without efficacy in this aggressive subtype. It is not as good as when you use the combination with HER2-targeted therapy, but it still works. Patients and clinicians in this era of biologic therapy immunotherapy tend to think only pricey medications are the ones that can be used for treatment and improving outcome. However, definitely adding help with targeted therapy is great whenever it's available. But if it's not available, chemotherapy still could be used in a sequential manner. We listed all possible chemotherapeutic options starting with taxanes, navelbine, platinums, even CMF, capecitabine. When it comes to second-line therapy, including those patients who relapse within 12 months of adjuvant therapy, the optimal line of treatment would be trastuzumab deruxtecan. However, if it's not available, we recommend to be offered with successive or progressive preference, if it's not available, T-DM1 could be used. If it's not available, capecitabine and lapatinib could be used. If it's not available, trastuzumab with chemotherapy could be used. If it's not available, we go back to the sequential use of chemotherapy, including adriamycin, taxanes, platinums, capecitabine, or even CMF. Brittany Harvey: I appreciate you reviewing those recommendations for HER2-positive breast cancer. So then, moving along, Dr. Arun, what are the recommendations for patients with metastatic triple-negative breast cancer? Dr. Banu Arun: Thank you, Brittany. Triple-negative breast cancer, of course, is one of the serious subgroups of breast cancer. About 10 to 15% of patients have triple-negative breast cancer. What I will do is I will divide it into the three-tier settings as well as first-, second-, and third-line therapies. For patients with triple-negative PD-L-negative metastatic breast cancer in the limited settings and even enhanced settings, single-agent chemotherapy rather than combination chemotherapy should be recommended as the first-line. However, if patients are symptomatic or have immediate life-threatening disease, combination chemotherapy can be offered. For patients with triple-negative breast cancer that are PD-L1 positive, they may be offered in addition to chemotherapy, an immune checkpoint inhibitor, as first-line therapy, most probably in enhanced settings and in basic and limited, of course, chemotherapy. When you move on to the second-line for metastatic breast cancer in patients with or without previous PD-L1 checkpoint inhibitors, clinicians can offer palliative or best supportive care in the basic setting. In the limited setting, chemotherapy with anthracyclines, taxanes, platinums are options. And in the enhanced setting if sacituzumab govitecan is not available, chemotherapy would be an option. Now, when we move on to the third-line setting for triple-negative breast cancer, clinicians can actually offer chemotherapy and/or palliative care, depending really on the status of the patient. Brittany Harvey: Excellent. Thank you for providing those recommendations for triple-negative breast cancer. As you mentioned, it's one of the rarer forms of breast cancer. So then, Dr. Al Sukhun, I'd like to move into the last section of patients, actually the most common, but hormone receptor-positive breast cancer. What are those recommendations? Dr. Sana Al Sukhun: Thank you, Brittany. As you mentioned, it's the most common subtype worldwide. The rule of the thumb is sequential hormonal therapy, depending on availability. So, whatever you have hormonal therapy, sequential hormonal therapy unless pending visceral crisis or symptomatic disease, it's recommended that you offer sequential single-agent chemotherapy, unless it's a real visceral crisis, where we recommend combination chemotherapy. That's a classic in all our guidelines. When considering frontline hormonal therapy, again, I will start from the maximal level and gradually recommend according to availability. So in enhanced levels in many countries now, we have generic CDK4/6 inhibitors, which increase their availability. So we do recommend hormonal therapy with CDK4/6 inhibitors. Upon progression or when they are not available, on progression, you move to the second line of hormonal therapy. If you have liquid biopsy, check for PIK3CA mutation. Sometimes you do have the liquid biopsy, but you do not have alpelisib to offer to your patients with hormonal therapy, then it's okay, you still can move to second-line fulvestrant with everolimus. Sequentially, you can move forward to fulvestrant by itself if you do not have everolimus. And even you can sequence tamoxifen until your patient stops responding to hormonal therapy then you can offer sequential single-agent chemotherapy. Brittany Harvey: Thank you, Dr. Al Sukhun for providing those recommendations. So then, Dr. Arun, what should clinicians do when we do not have access to receptor assessment? What is recommended for best practices for management of those patients? Dr. Banu Arun: So, Brittany, that's an important question. There are some basic settings where unfortunately, immunohistochemistry for ER/PR HER2neu determination is not available. Our group really recommends in these cases that clinicians may presume hormonal receptor positivity and offer tamoxifen in most cases. It is expected that IHC would be available in limited and, of course, enhanced settings. Brittany Harvey: Great. Thank you for providing that information. So further, what else should clinicians know as they implement these recommendations, Dr. Arun? Dr. Banu Arun: It's very important that we, all healthcare provider clinicians, really know the data. I think reading the guidelines or knowing about first and second line therapies is obviously important, but the devil is in the details. And I think knowing the publications and subgroup analyses, if needed, because every patient is different and sometimes the recommendations cannot go by the books. You really need to do an assessment of the patient and see in which setting you are and then make the most of the guidelines that are recommended. It's to guide. The name is guidelines. It's to guide. And ultimately, it's the clinician's responsibility to find the best available therapy for the patient. And sometimes that includes no treatment and supportive care. Dr. Sana Al Sukhun: Totally agree with Dr. Arun. They are there to support the clinician decision. After all, the clinician is the one who sees the patient, who can evaluate the patient from all aspects — social aspect, physical aspect, the tumor aspect. So it's not just about the tumor, it's about the patient and the environment where the clinician is treating the patient. However, I believe there is support to the clinician not only in treating the patient, but also on addressing priorities for research to improve outcomes for patients in different resource settings. There is also support for the clinicians to help them advocate for improving care for patients in a strategic way, where they prioritize resource allocation. So they are there to support the clinician at all levels, not only when treating patients, but when advocating for patients, when helping patients to make decisions, when they're discussing with their health officials and policymakers. Brittany Harvey: Absolutely. Those are excellent points that you both made about individualizing patient care for the specific person in front of you. So then, finally, Dr. Al Sukhun, how will these guideline recommendations impact patients with metastatic breast cancer globally? Dr. Sana Al Sukhun: The ultimate goal for anything we do, including guidelines, is to improve outcomes for patients worldwide. They are there to support clinician decisions, empower clinicians to optimize care for their patients, to advocate for improving outcomes for patients by strategically allocating resources according to the most impactful strategy. They help clinicians to identify areas for research that are needed according to the resources available to them. They are there to guide policymakers, again, also implementing strategies to implement science that could improve outcomes in an efficient way for their societies. So hopefully, all these, with our research, with our advocacy, with our health policy, with our treatment decisions, hopefully all these will improve outcomes for breast cancer patients and ultimately reduce mortality, particularly in less fortunate, limited resource settings for patients everywhere. Brittany Harvey: Absolutely. We hope that these guidelines improve outcomes and quality of life for patients worldwide. So I want to thank you both so much for your work to develop this guideline. There's certainly a large amount of recommendations, so I encourage our listeners to read the full guideline, which is linked in the show notes. And I want to thank you so much for your time today, Dr. Al Sukhun and Dr. Arun. Dr. Sana Al Sukhun: Thank you for having us. Dr. Banu Arun: Thank you, Brittany. Brittany Harvey: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/resource-stratified-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
In discussion with Dr. Hope Rugo, covering the San Antonio Breast Cancer Symposium 2023 Highlights from Community Oncology perspective. We covered 4 important practice informing studies with Dr. Rugo: - NATALEE Update – Ribociclib + Nonsteroidal AI as Adj Treatment in Patients with HR+/HER2− Early Breast Cancer: Final iDFS analysis - MONARCH 3 – Final OS Results of Abemaciclib Plus a Nonsteroidal AI as First-line Therapy for HR+, HER2– Advanced Breast Cancer - INAVO120 – Phase III Study of Inavolisib or Placebo in Combination with Palbociclib and Fulvestrant in Patients with PIK3CA-mut, HR+, HER2– Locally Adv/Metastatic Breast Cancer - TROPION-Breast01 – Phase III Study of Dato-DXd vs Chemo for Patients with Previously Treated Inoperable/Metastatic HR+, HER2– Breast Cancer
Dr Gradishar discusses the FDA approval of capivasertib plus fulvestrant for patients with advanced HR-positive, HER2-negative breast cancer harboring PIK3CA, AKT1, or PTEN alterations.
San Antonio Breast Cancer Symposium is here, and this year, OFTIM (Oncology for the Inquisitive Mind) is bringing you the latest and greatest in all things breast cancer. With over 10000 attendees, the research and vibrant discussions did not disappoint, with updates, controversies and complexities. Taking centre stage were PIK3CA mutation treatments, updates on CDK4/6 inhibitors and the age-old question - does exercise improve outcomes for our patients?Studies discussed in today's episode (subscription may be required)MONARCH-3KATHERINEINAVO120PREFERABLE EFFECTFor more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.
Guest: Megan Kruse, MD While intrinsic mutations, like PIK3CA, are present at the outset and can be identified upfront in patients with HR+/HER2- metastatic breast cancer, acquired mutations, like ESR1, cannot be detected on baseline tumor profiling. That's why longitudinal monitoring with liquid biopsies over the course of treatment is required. Learn more about these key differences in testing for acquired versus intrinsic mutations with Dr. Megan Kruse, a breast medical oncologist at the Cleveland Clinic.
Dr. Angie DeMichele and Dr. Lynn Henry present the latest rapid recommendation impacting two ASCO guidelines. This update focuses on testing for ESR1 mutations in patients with hormone receptor-positive, HER2-negative metastatic breast cancer, and presents treatment recommendations for patients with a detectable ESR1 mutation. Dr. DeMichele and Dr. Henry review the recent data from the EMERALD trial, discuss it's implications for practice, and ongoing developments they're monitoring for more effective therapeutic options. Read the latest update, "Testing for ESR1 Mutations to Guide Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update at www.asco.org/breast-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the update and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.2300638 Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Angie DeMichele from University of Pennsylvania, and Dr. Lynn Henry from the University of Michigan, authors on ‘Testing for ESR1 Mutations to Guide Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update'. Thank you for being here, Dr. DeMichele and Dr. Henry. Dr. Angie DeMichele: It's a pleasure. Dr. Lynn Henry: Thank you. Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including our guests on this podcast episode today, are available online with a publication of the rapid recommendation update in the Journal of Clinical Oncology, which is linked in the show notes. So then, getting into the content of this rapid recommendation first, Dr. Henry, what prompted this rapid update, which provides updated recommendations for two ASCO guidelines? First, the ‘Biomarkers for Systemic Therapy and Metastatic Breast Cancer Guideline', last published in 2022, and the ‘Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer Guideline', which was last updated in 2021. Dr. Lynn Henry: Thank you, Brittany. There's been a lot of exciting news for the treatment of metastatic breast cancer in the last few years. This particular update reflects the results of the phase III EMERALD trial. This trial compared the new oral selective estrogen receptor degrader, elacestrant, to standard-of-care endocrine therapy with either fulvestrant or an aromatase inhibitor in patients with hormone receptor-positive, HER2-negative metastatic breast cancer that had previously progressed during treatment with a CDK4/6 inhibitor in combination with endocrine therapy. Compared to standard-of-care, in this trial, they showed improved progression-free survival in both the overall study population as well as specifically in the patients who had a detectable ESR1 mutation in their circulating tumor DNA. These findings were published in the Journal of Clinical Oncology in 2022, and the drug was subsequently approved by the US Food and Drug Administration in January 2023. Therefore, we felt that it was important to update the guidelines to reflect the results of this trial and the new drug approval. Brittany Harvey: Excellent. Thank you for describing the results of that trial and the new approval. So then, based on this data, Dr. DeMichele, what is the updated recommendation from the guideline expert panel for testing for ESR1 mutations? Dr. Angie DeMichele: So, the guideline panel has now recommended that ESR1 mutation testing occur for any patient who develops a recurrence or progression on endocrine therapy. And this is specifically in reference to the development of ESR1 mutations that can occur after a patient has been exposed to aromatase inhibitors. The guideline itself recommends that this testing be done on either tumor or blood, but blood is preferable because there is increased sensitivity using ctDNA testing over tumor testing. So this was an important component of the change in the recommendation because it's linked to the approval of elacestrant as a therapy. Patients are only eligible to receive elacestrant if they harbor an ESR1 mutation. Brittany Harvey: Understood. I appreciate that explanation. So then, Dr. Henry, following that recommendation for testing, what is the new recommendation for treatment for patients with a detectable ESR1 mutation? Dr. Lynn Henry: Yes. So patients who have a detectable ESR1 mutation and who have previously received treatment with endocrine therapy in combination with the CDK4/6 inhibitor for advanced breast cancer now have multiple treatment options. The newest option is this new drug, elacestrant, which is given 345 milligrams orally daily. There are still the other options that we already knew about, which include a different endocrine therapy alone, such as fulvestrant or an aromatase inhibitor, or possibly an endocrine therapy in combination with a targeted agent, such as alpelisib or everolimus. And those decisions really need to be based on what other mutations are present in the patient's cancer. Importantly, at this time, there are no safety or efficacy data to support using elacestrant in combination with targeted agents. Therefore, to date, it has only been approved to be used as monotherapy. But really, this is an exciting new potential option for treatment for patients whose tumors have a detectable ESR1 mutation. Brittany Harvey: Yes, this is an exciting option, and I appreciate you describing how this fits in with the existing treatment paradigm for these patients. So then, Dr. DeMichele, as these new recommendations are implemented, what should clinicians know? Dr. Angie DeMichele: I think this is a really important new step in breast cancer in testing for ESR1 mutations. We've not previously had a medication that required the existence of an ESR1 mutation for patients to be eligible for therapy. So obtaining ESR1 mutation testing may be new for some clinicians. As I stated earlier, this can be done either on a tumor biopsy or on blood testing using the Guardant360 ctDNA test, which is the test that was used in the clinical trial. And it was stated that the ctDNA test is more sensitive than the tumor test. But what's really important here is that the testing occur at the time that the clinician is considering switching therapies, because it's important to find that ESR1 mutation prior to starting the next therapy. ESR1 mutations don't typically exist in a tumor at the time it's diagnosed. They only emerge over time after patients have been exposed to different endocrine therapies, particularly aromatase inhibitors. It's also possible that at the time of a recurrence after aromatase inhibitor therapy or progression on an aromatase inhibitor, there will not be any detectable ESR1 mutation. However, with subsequent therapy, an ESR1 mutation can occur. So a patient may need serial testing over time to determine whether an ESR1 mutation has developed. Brittany Harvey: Understood. Those are important clinical implications. So then, Dr. Henry, Dr. DeMichele just described some of the testing implications for patients. But in your view, how does this rapid update impact patients with hormone receptor-positive, HER2-negative metastatic breast cancer? Dr. Lynn Henry: So as Dr. DeMichele mentioned, this update specifically highlights approval of a new drug, oral SERD elacestrant. This is an exciting new option for treatment of patients whose tumors have an ESR1 mutation. So previous data have demonstrated that cancers with ESR1 mutations do not respond as well to previously available standard-of-care treatments such as aromatase inhibitors. It's nice to have a drug that may be a better option than some of the previously existing treatments for hormone receptor-positive, HER2-negative metastatic breast cancer. Brittany Harvey: Definitely. That's great to hear. So then, finally, Dr. DeMichele, are there ongoing research developments that the panel is monitoring for future updates to these guidelines? Dr. Angie DeMichele: We certainly are monitoring additional research developments, Brittany. Specifically, there are numerous other selective estrogen receptor degraders that are being tested, and these also may ultimately require ESR1 mutation testing and detection for therapies. So we'll be monitoring the results of those clinical trials. We'll also be watching for additional trials that help us understand how to best utilize elacestrant and whether it can be combined with other therapies. And then, finally, I think we have to think about how to place this in the context of other types of molecular changes that we may detect in metastatic breast cancer, such as PIK3CA mutations and others. And as we move forward, I anticipate that we will have additional therapies that are specifically targeted to molecular changes in the tumor. And I think this is a really exciting development because this is a major step forward toward precision medicine, where we're really tailoring the therapy to the specific biology of the patient's tumor and actually responding to the ways in which the tumor is evolving over time and in response to treatment. So as tumors become increasingly resistant to therapies, we can actually take advantage of those resistance mechanisms to develop therapies that will be more effective. Brittany Harvey: Yes, we'll look forward to those new therapies and research developments and then updated guidelines in the future. So I want to thank you both so much for your work on this rapid recommendation update and for your time today, Dr. DeMichele and Dr. Henry. Dr. Angie DeMichele: Thank you. Dr. Lynn Henry: Thank you very much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guidelines, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the newly redesigned ASCO Guidelines app, available for free in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this Podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Featuring perspectives from Drs Aditya Bardia, Matthew Goetz, Virginia Kaklamani, Kevin Kalinsky and Hope Rugo, including the following topics: Current Role of Genomic Assays for Hormone Receptor (HR)-Positive Localized Breast Cancer Introduction (0:00) Case: A premenopausal woman in her early 40s with 9-mm, Grade III, ER/PR-positive, HER2-negative, node-negative infiltrating ductal carcinoma (IDC) – 21-gene Recurrence Score® 22 — Alan B Astrow, MD (3:39) Case: A premenopausal woman in her mid 30s with 3.6-cm, ER/PR-positive, HER2-low (IHC 1+), sentinel node-positive (4/4) multifocal IDC after bilateral mastectomies, adjuvant AC-T and ovarian function suppression (OFS)/aromatase inhibitor, Ki67 50% — Laila Agrawal, MD (9:40) Dr Goetz presentation (19:43) Optimizing the Management of Localized ER-Positive Breast Cancer Case: A woman in her early 40s with 5.5-cm, ER/PR-positive, HER2-negative, node-positive (20/21) IDC after bilateral mastectomies, bilateral salpingo-oophorectomy, adjuvant AC-T and initiation of letrozole/abemaciclib, Ki-67 3% — Susmitha Apuri, MD (32:22) Case: A woman in her mid 50s with de novo ER-positive, PR-negative, HER2-negative ulcerated breast cancer with pulmonary and extensive spinal metastases — Jennifer L Dallas, MD (40:45) Dr Kaklamani presentation (45:32) Selection and Sequencing of Therapy for Patients with ER-Positive Metastatic Breast Cancer (mBC) Case: A woman in her early 50s with ER/PR-positive, HER2-low mBC with a PI3KCA mutation who experiences a dramatic response to rechallenge with fulvestrant and a CDK4/6i (abemaciclib); now with progression and cytopenias — Kapisthalam (KS) Kumar, MD (59:07) Dr Kalinsky presentation (1:09:53) Recent Appreciation of HER2 Low as a Unique Subset of HR-Positive Breast Cancer Case: A premenopausal woman in her late 30s with ER/PR-positive, HER2-low (IHC 1+) IDC after adjuvant tamoxifen and OFS x 5 years, now with bone and liver metastases — Dr Agrawal (1:19:45) Dr Bardia presentation (1:24:29) Novel Strategies Under Investigation for Patients with HR-Positive mBC Case: A woman in her early 90s with ER/PR-positive, HER2-low (IHC 1+) mBC and progressive disease on multiple lines of endocrine and chemotherapy receives T-DXd — Dr Astrow (1:38:44) Case: A woman in her mid 40s with ER/PR-positive, HER2-low (IHC 2+) mBC who has received fulvestrant/abemaciclib, now receiving exemestane/everolimus – ESR1 and PIK3CA mutations — Dr Dallas (1:44:15) Dr Rugo presentation (1:49:58) CME information and select publications
Featuring perspectives from Drs Erika Hamilton, Sara Hurvitz, Ian Krop, Shanu Modi and Sara Tolaney, including the following topics: Optimizing the Management of Localized HER2-Positive Breast Cancer Introduction (0:00) Case: A woman in her mid 60s with pulmonary hypertension and triple-positive, node-positive infiltrating ductal carcinoma (IDC) after neoadjuvant TCHP and clinical complete remission — Susmitha Apuri, MD (4:31) Case: A woman in her early 60s with a 1.7-cm, triple-positive, clinically node-negative IDC — Ranju Gupta, MD (10:05) Dr Tolaney presentation (18:44) Current Considerations in the Treatment of HER2-Positive Metastatic Breast Cancer (mBC) Case: A woman in her early 60s with an 8-cm, ER-negative, PR-positive, HER2-positive IDC and positive nodes bilaterally after neoadjuvant TCHP and bilateral mastectomies with no residual disease — Henna Malik, MD (31:12) Case: A woman in her late 50s with Stage IIIA, ER/PR-negative, HER2-positive, node-positive IDC with residual disease after neoadjuvant TCHP and mastectomy — Laila Agrawal, MD ()35:29 Dr Krop presentation (42:56) Management of HER2-Positive Breast Cancer with CNS Metastases Case: A woman in her early 90s with “mild” dementia and ER/PR-negative, HER2 IHC 1+ IDC with symptomatic chest wall recurrence after neoadjuvant paclitaxel/trastuzumab and lumpectomy — Alan B Astrow, MD (54:54) Case: A woman in her late 40s with a triple-positive multifocal IDC with a gBRCA2 mutation and HER2-negative axillary nodes after neoadjuvant TCHP and bilateral mastectomies with significant response in the breast but 49 positive nodes — Zanetta S Lamar, MD (1:00:01) Dr Hamilton presentation (1:06:51) Recent Appreciation of HER2 Low as a Unique Disease Subset; Future Directions in the Management of HER2-Positive and HER2-Low Breast Cancer Cases: A premenopausal woman in her late 30s with a triple-positive IDC who develops brain metastases while receiving THP; A woman in her late 60s with an ER/PR-negative, HER2-positive IDC who develops brain metastases after first-line THP and second-line T-DM1 — Kelly Yap, MD & Rohit Gosain, MD (1:20:46) Case: A woman in her mid 60s with ER/PR-negative, HER2-positive mBC treated with paclitaxel/trastuzumab, then T-DXd on progression — Joanna Metzner-Sadurski, MD (1:29:40) Dr Modi presentation (1:40:51) Incidence and Management of Adverse Events Associated with HER2-Targeted Therapy Case: A woman in her early 60s with recurrent triple-positive mBC whose disease converts to HER2-negative, PIK3CA-positive at the time of progression — Dhatri Kodali, MD (2:01:10) Dr Hurvitz presentation (2:05:08) CME information and select publications
Guillaume Canaud, MD, PhD, of the Paris Descartes University, explains why it is important to regularly measure objective outcomes in persons with PiK3CA-related overgrowth syndrome (PROS).PROS is a group of rare congenital disorders that lead to the overgrowth of parts of the body. PROS is caused by gain of function mutations in the PIK3CA gene. Specific disorders under the umbrella of PROS include fibroadipose hyperplasia, hemihyperplasia multiple lipomatosis (HHML), CLOVES syndrome, macrodactyly, fibroadipose infiltrating lipomatosis, megalencephaly-capillary malformation (MCAP), and dysplastic megalencephaly (DMEG).
Scientific Sense ® by Gill Eapen: Prof Trey Ideker is Professor of Medicine, Bioengineering and Computer Science at the University of California, San Diego. He directs the National Resource for Network Biology, and the Cancer Cell Map and Psychiatric Cell Map Initiatives. A multi-scale map of cell structure fusing protein images and interactions. Nature. 2021 Nov 24. doi: 10.1038/s41586-021-04115 “We Might Not Know Half of What's in Our Cells, New AI Technique Reveals Interpretation of cancer mutations using a multiscale map of protein systems. Science. 2021 A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity. A protein interaction landscape of breast cancer. Science. 2021 Oct;374(6563):eabf3066 “Studies Delve Deep into the Protein Machinery of Cancer Cells.” NCI (4 Nov 2021) “From COVID to cancer, gene-mapping tool could ‘revolutionize' treatment“. SF Chronicle (2 Oc “Moonshot Project Aims to Understand and Beat Cancer Using Protein Maps“. Singularity Hub (5 Oct 2021) “Looking Beyond DNA to See Cancer with New Clarity,” Predicting Drug Response and Synergy Using a Deep Learning Model of Human Cancer Cells. Cancer Cell (2020), https://doi.org/10.1016/j.ccell.2020.09.014. PMID: 33096023. [PDF] [PubMed] Related Press: UCSD Health, AZoLifeSciences, Med India, Health IT Analytics and ScienceDaily. Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome. Cell Systems. 2020 Aug 26;11(2):176-185.e6. doi: 10.1016/j.cels.2020.06.006. Epub 2020 Jul 2. PMID: 32619550 [PDF] [PubMed] *Cover Article Related Press: Here's a better way to convert dog years to human years, scientists say. Science Magazine (15 Nov 2019). See also: Scientific American, BBC, NPR, Washington Post, Discover Magazine, Smithsonian, New York Post, (and more) Identifying Epistasis in Cancer Genomes: A Delicate Affair. Cell. 2019 May 30;177(6):1375-1383. doi: 10.1016/j.cell.2019.05.005. Review. PMID: 31150618 [PDF] [PubMed] Using deep learning to model the hierarchical structure and function of a cell.* Nat Methods. 2018 Mar 5. doi: 10.1038/nmeth.4627. PMID: 29505029 [PDF] [PubMed] [Cover Art] *Cover article Please subscribe to this channel: https://www.youtube.com/c/ScientificSense?sub_confirmation=1 --- Send in a voice message: https://anchor.fm/scientificsense/message Support this podcast: https://anchor.fm/scientificsense/support
La Dra. Leticia Vázquez Cortés, oncóloga médica adscrita al Instituto Mexicano del Seguro Social en Morelia, Michoacán, México, nos comenta sobre lo más destacado en tumores del sistema nervioso central (SNC) presentados durante el Congreso Anual de ESMO 2022 en París, Francia. Resumen 2770: Estudio fase I/IIa, ReSPECT-GMB, de escalación de dosis, para determinar la seguridad y la dosis recomendada de rhenium-186 nanoliposomal en pacientes con glioma recurrente. Resumen 2780: Resultados preliminares del estudio fase II de retifanlimab (inhibidor de PD-1) con o sin epacadostat (inhibidor de IDO1) en combinación con bevacizumab y radioterapia hipofraccionada para pacientes con glioblastoma recurrente. Resumen 2790: Estudio prospectivo y multicéntrico con secuenciación de última generación de alto rendimiento con un panel de genes personalizado (8 genes: IDH1, IDH2, ATRX, Tp53, PTEN, PIK3CA, EGFR, BRAF) para detección de ADN tumoral circulante en líquido cefalorraquídeo y concordancia con el tumor primario en pacientes con glioma. Resumen 2800: Resultados finales del estudio fase II sobre farmacocinética y farmacodinamia de paxalisib en pacientes con glioblastoma recién diagnosticados con estado de promotor del gen MGMT no metilado. Fecha de grabación: 15 de septiembre de 2022. Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.
(00:32) Could you provide a little bit of background about yourself, please?(01:01) Please give us a brief overview of the new PIK3CA assay. (02:09) Why do we offer two different tests, and when should each be ordered?(03:58) Which patients should have this testing?(04:39) Is this testing used for patients being considered for second-line treatment after first-line hormone receptor treatment?(05:20) Is there anything else you would like to add about the PIK3CA testing?(06:23) Why is it important to know the molecular signature of these tumors?
CME credits: 0.50 Valid until: 25-08-2023 Claim your CME credit at https://reachmd.com/programs/cme/evolving-perspectives-in-pik3ca-related-overgrowth-spectrum-diagnosis-treatment/13790/ PIK3CA-related overgrowth spectrum (PROS) refers to various clinical entities that share the same pathogenetic mechanism. These disorders are caused by somatic gain-of-function PIK3CA mutations. Diagnosis of PROS is often challenging and requires DNA sequencing of the affected tissue. PIK3CA genetic mutations vary greatly depending on the tissue being tested. PROS is not considered an inherited disease. The road to a diagnosis of a rare disease can be a long, winding process. Because of its rarity, a wide spectrum of symptoms, and disease heterogeneity, patients may feel alone and as though they are the only ones with the disease. Management of PROS currently involves symptomatic treatment of its manifestations; an unmet need exists for targeted, systemic therapies. Currently, there is no cure for PROS. This educational activity will assist the interprofessional care team to better understand, apply, and interpret advances in current and emerging evidence that will help bridge the gap toward faster adoption into patient care.
CME credits: 0.50 Valid until: 25-08-2023 Claim your CME credit at https://reachmd.com/programs/cme/evolving-perspectives-in-pik3ca-related-overgrowth-spectrum-diagnosis-treatment/13790/ PIK3CA-related overgrowth spectrum (PROS) refers to various clinical entities that share the same pathogenetic mechanism. These disorders are caused by somatic gain-of-function PIK3CA mutations. Diagnosis of PROS is often challenging and requires DNA sequencing of the affected tissue. PIK3CA genetic mutations vary greatly depending on the tissue being tested. PROS is not considered an inherited disease. The road to a diagnosis of a rare disease can be a long, winding process. Because of its rarity, a wide spectrum of symptoms, and disease heterogeneity, patients may feel alone and as though they are the only ones with the disease. Management of PROS currently involves symptomatic treatment of its manifestations; an unmet need exists for targeted, systemic therapies. Currently, there is no cure for PROS. This educational activity will assist the interprofessional care team to better understand, apply, and interpret advances in current and emerging evidence that will help bridge the gap toward faster adoption into patient care.
Featuring perspectives from Prof Ghassan Abou-Alfa, including the following topics: Introduction (0:00) Case: A woman in her early 50s with metastatic hepatoid carcinoma of the ovary with an FGFR fusion — Syed M Ahmed, MD, PhD (2:56) Key recent data sets (5:59) Case: A man in his mid 60s with a history of Child-Pugh B cirrhosis and Grade 1 esophageal varices who is receiving atezolizumab/bevacizumab for multifocal HCC — Raji Shameem, MD (22:28) Case: A man in his late 60s with previously treated HCC cirrhosis who is now diagnosed with potentially resectable HCC — Syed F Zafar, MD (29:30) Case: A woman in her late 70s receiving adjuvant anastrozole for Stage I breast cancer who is now receiving atezolizumab/bevacizumab for metastatic HCC — Sunil Gandhi, MD (33:41) Case: A man in his late 70s with metastatic HCC and portal vein thrombosis receiving atezolizumab/bevacizumab (NGS [next-generation sequencing] with PIK3CA mutation, PD-L1 50%) — Susmitha Apuri, MD (35:47) Management of Biliary Tract Cancers (40:18) Case: A man in his late 50s with resected Stage IIB gallbladder cancer s/p adjuvant capecitabine who now has metastatic disease (HER2-positive; MSS, PD-L10) — Nasfat Shehadeh, MD (44:01) Case: A woman in her early 40s with a history of ductal carcinoma in situ and family history of breast cancer, now with metastatic cholangiocarcinoma (NGS with IDH2 mutation) — Joanna Metzner-Sadurski, MD (53:41) CME information and select publications
An interview with Dr. Lynn Henry from the University of Michigan in Ann Arbor, MI, lead author on "Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update." Dr. Henry reviews new biomarkers for the purposes of making treatment decisions for triple-negative breast cancer, and hormone receptor-positive, HER2-negative breast cancer, as well as tumor agnostic tumor biomarkers. Specific biomarkers addressed in this conversation include PIK3CA, ESR1, BRCA 1/2, PALB2, HRD, PD-L1, dMMR/MSI-H, TMB, NTRK, ctDNA, and CTCs. Read the full guideline at www.asco.org/breast-cancer-guidelines. TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs, covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Lynn Henry from the University of Michigan in Ann Arbor, Michigan, lead author on 'Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update'. Thank you for being here, Dr. Henry. Dr. Lynn Henry: Thank you very much for inviting me to participate. Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Henry, do you have any relevant disclosures that are related to this guideline topic? Dr. Lynn Henry: No, I do not. Brittany Harvey: Great! Thank you. Then let's talk about the scope of this guideline. So, what prompted this update to the guideline on the use of biomarkers to guide decisions on systemic therapy for patients with metastatic breast cancer, which was last updated in 2015? And what is the scope of this guideline update? Dr. Lynn Henry: Yes, so a lot has happened in the past six or seven years that influence how we treat metastatic breast cancer. And there are many new drugs that have been approved by the FDA during that time. When we reviewed the prior guideline and the new treatment landscape, we realized that while much of what was included in the old guideline was still relevant, there were quite a number of new biomarkers related to new drugs that needed to be included. The newly recommended biomarkers are primarily applicable to making decisions about treatment of estrogen receptor, progesterone receptor, and HER2-negative breast cancer, also called triple-negative breast cancer, as well as for treatment of hormone receptor-positive HER2-negative breast cancer. And finally, there are now some tumor biomarkers that can be tested for that are tumor agnostic, and these were included as well. Brittany Harvey: Great! So, then let's discuss the updated guideline recommendations based off these new biomarkers for our listeners. The guideline reviews testing for several different biomarkers. So, I would like to review each of the biomarkers that the panel assessed. Let's start with what is the role of PIK3CA mutation testing? Dr. Lynn Henry: Yeah! So, PIK3CA activating mutations are commonly found in tumors that are hormone receptor-positive and HER2-negative. Based on the results of the SOLAR-1 trial, patients whose tumors have an activating PIK3CA mutation had improved progression-free survival when treated with the PI3 kinase inhibitor alpelisib plus fulvestrant compared to fulvestrant alone. This improvement was not seen in patients whose cancers didn't have a mutation. So, therefore, this provided the evidence for the clinical utility of evaluating tumors for the somatic PIK3CA mutations. Testing of either a tumor specimen or plasma to look for PIK3CA mutations can be performed. However, it's important that if the plasma is tested, and no PIK3CA mutations are identified in the circulating tumor DNA, then our tumor specimen should really be tested if possible, because of the possibility of a false negative finding in the plasma. Also, since these mutations can be acquired over time, a more recent specimen should be tested if possible, as opposed to testing the primary tumor. Finally, in the SOLAR-1 trial, a patient's tumor had to have one of the 11 pre-specified PIK3CA mutations in exon 7, 9, or 20. And therefore, when mutations are identified using next-generation sequencing, it is important to confirm that the identified mutation is one of those 11 activating mutations and not a different one that may not convey benefit from treatment with a PI3 kinase inhibitor. Brittany Harvey: Great! I appreciate you're reviewing that recommendation, as well as the clinical utility of it and the evidence behind it. So, then following those recommendations, what is the role of testing for ESR1 mutations? Dr. Lynn Henry: At this time, there are insufficient data to support routine testing of metastatic hormone receptor-positive HER2-negative tumors for ESR1 mutations. However, the panel did note that there's a retrospective analysis of two different phases three trials that demonstrated that fulvestrant improved progression-free survival compared to the aromatase inhibitor exemestane in patients who had previously progressed on a non-steroidal AI and whose tumors had an ESR1 mutation. Importantly, there are ongoing clinical trials addressing this issue, including the PADA-1 trial, which is evaluating the effect of the switch of fulvestrant from aromatase inhibitor therapy, versus remaining on that therapy when ESR1 mutations are detected in the blood. However, although preliminary findings were presented at a recent large breast cancer meeting, and were suggestive of a possible progression-free survival benefit from switching therapy, data have not yet been published, and therefore they were not included in this guideline. Brittany Harvey: Great! So, we'll look forward to those updated data to potentially review that recommendation in the future. So, following those recommendations, what is the role of testing for germline BRCA 1 or 2 and PALB2 pathogenic mutations? Dr. Lynn Henry: So, the answer for germline BRCA1 and BRCA2 mutations is relatively straightforward. Patients with metastatic HER2-negative breast cancer can be either hormone receptor-positive or negative, and who are candidates for treatment with a PARP inhibitor should undergo testing for germline BRCA1 and BRCA2 pathogenic or likely pathogenic mutations to determine whether they should receive treatment with a PARP inhibitor. This recommendation is based on the results of two large randomized clinical trials comparing PARP inhibitor therapy to physician's choice chemotherapy, although notably, the chemotherapy options did not include taxanes, anthracyclines, or platinums. In contrast, there remains insufficient evidence to support a recommendation either for or against testing for germline PALB2 pathogenic variant for the purpose of determining eligibility for treatment with a PARP inhibitor. The panel did note, however, that there are small single-arm studies that show that there is high response rate to PARP inhibitors in patients with metastatic breast cancer and coding DNA repair defects, such as either germline PALB2 pathogenic variants or somatic BRCA1 or 2 mutations. It was also noted that it is likely that patients who harbored mutations in these genes will actually be identified through routine testing with panel testing for germline variants. Brittany Harvey: Okay, understood. So, then following those recommendations, what is the role of testing tumors for homologous recombination deficiency? Dr. Lynn Henry: So, although there are emerging data from other solid tumors to support the use of homologous recombination deficiency, or HRD testing to guide therapy, current data do not support the assessment of HRD in the management of metastatic breast cancer. Therefore, we did not recommend routine testing of tumors for HRD at this time. Brittany Harvey: It's important to note where we both have evidence and where we don't have evidence. So, then what is the role of testing for expression of PD-L1 in metastatic breast cancer? Dr. Lynn Henry: So, the panel recommends that patients who are candidates for treatment with immunotherapy, with either a PD1 or PD-L1 inhibitor, should undergo testing for expression of PD-L1 in the tumor and immune cells with an FDA-approved test. At present in the United States, pembrolizumab is the only approved immunotherapy for the treatment of metastatic breast cancer, and it is given in combination with chemotherapy. The FDA-approved test for this drug is the 22C3 assay which evaluates PD-L1 staining in the tumor and surrounding stroma to calculate a combined positive score or CPS, with positive considered to be a score of 10 or greater. Of note, in other countries, there are different anti PD1 and PD-L1 antibodies that are approved for treatment, and each has been approved with its own companion diagnostic. So, it is important to make sure that you're using the right biomarker test, depending on which drug you are planning to use. Brittany Harvey: Great! I appreciate you reviewing the test in addition to the role of the biomarker. So, then, following those recommendations, what is the role of testing for deficient mismatch repair microsatellite instability-high? Dr. Lynn Henry: Similar to PD-L1 testing, it is recommended that patients with metastatic breast cancer who are candidates for a treatment regimen that includes an immune checkpoint inhibitor should undergo testing for deficient mismatch repair or microsatellite instability-high to determine eligibility for treatment with one of the drugs that is currently FDA approved, either dostarlimab or pembrolizumab. In contrast to the PD-L1 data, however, there are no randomized studies that have been conducted specifically in patients with breast cancer addressing this question. The testing recommendation was therefore included in these guidelines because of the tumor agnostic FDA approval of these drugs. In terms of which biomarker methodology to use, it was noted that, while the original studies assessed the deficient mismatch repair and MSI high using immunochemistry, and PCR respectively. The FDA has subsequently approved the next-generation sequencing platform to use in selecting candidates for these treatments. And so, therefore, there are a number of different tests that can be used. Brittany Harvey: Thank you for reviewing those recommendations as well. So, then following, what is the role of testing for tumor mutational burden? Dr. Henry Lynn: So, tumor mutational burden describes the quantity of somatic mutations in the tumor. Similar to the biomarkers we were previously discussing, there are minimal data specifically in metastatic breast cancer to support the assessment of tumor mutational burden for making treatment decisions. However, the testing recommendation was again included in the guidelines because of the tumor agnostic FDA approval of the drug pembrolizumab in the setting of high TMB. And also there is one single arm phase two trial that looked at this specifically. Importantly, the panel noted that there are a variety of factors that influence assessment of TMB. These include sample type, pre-analytical factors so how the sample was handled, the size of the panel and mutations that are tested, depths of the sequencing, type of the mutations that are included on the panel, and cut point variables. So, in particular, assessment of TMB in cell-free DNA assays such as circulating tumor DNA is an area of evolving evidence. There are therefore very important caveats to be aware of when selecting a TMB assay and assessing the results, many of which are outlined in the guideline manuscript itself, and different assays can yield different results for the same tissue specimen. It is therefore very important to use the approved companion assay and the approved cut point when making decisions regarding a specific treatment. Brittany Harvey: Absolutely. I appreciate your reviewing those details. So, then what is the role of testing for neurotrophic tyrosine receptor kinase? Dr. Lynn Henry: So, I'm going to abbreviate that to NTRK. So, NTRK fusions are rare in metastatic breast cancer. One study said 0.39% of all breast cancers have NTRK fusions. So, as with the above biomarkers, the NTRK testing recommendation is based on the results of phase 1 and phase 2 studies that were identified by the panel evaluating the efficacy and safety of these inhibitors for the treatment of advanced solid tumors with NTRK gene fusions, noting that there are only minimal data available that are specific to metastatic breast cancer. Brittany Harvey: Understood. Some of these are very rare in metastatic breast cancer. So, then, following that recommendation, what is the role of using circulating tumor DNA? Dr. Lynn Henry: So, for circulating tumor DNA, although the ctDNA technology holds promise in metastatic disease, for its ability to potentially identify tumor-specific mutations that are shed into the blood and that may be targetable, to date, neither the measurement of changes in ctDNA as a marker of treatment responsiveness nor identification of specific mutations in the blood to direct therapy has actually been prospectively shown to improve patient outcomes compared to standard imaging-based detection of tumor progression. Therefore, at present, the guideline does not recommend routine assessment of ctDNA for monitoring response to therapy among patients with metastatic breast cancer, although many studies are underway evaluating this question. Brittany Harvey: Understood. Then the last biomarker that the panel assessed in this guideline update, what is the role of using circulating tumor cells? Dr. Lynn Henry: Similar to circulating tumor DNA, there are insufficient data to recommend routine use of circulating tumor cells to monitor response to therapy among patients with metastatic breast cancer. To date, studies that have examined the clinical utility of this marker to determine the optimal time for treatment change have not led to improvements in outcomes in metastatic breast cancer. Brittany Harvey: Great! Well, thank you for reviewing all of these recommendations. The panel certainly took on a lot of biomarkers and performed a critical review of all the evidence to make recommendations in this setting. So, in your view, Dr. Henry, what is the importance of this guideline update and what should clinicians know as they implement these updated recommendations? Dr. Lynn Henry: Yeah, that's an excellent question. So, this guideline addresses the key questions that we face, as we're making decisions about how best to treat patients with metastatic breast cancer. Importantly, the guideline highlights the current state of the science, with a focus on the available published data from randomized clinical trials. It also discusses the limitations of our current knowledge, as well as key considerations for different biomarkers. Of course, we recognize that there are new data emerging on a regular basis. And the panel therefore also highlighted where data are anticipated but not yet available, as well as key questions which we hope will be able to be addressed in the more distant future. Brittany Harvey: And then finally, how will these guideline recommendations affect patients with metastatic breast cancer? Dr. Lynn Henry: Yeah, so really, that is the bottom line, isn't it? So, ideally, this guideline will enable the dissemination of best practices in terms of biomarker selection and analysis to guide clinicians as they are making treatment decisions in conjunction with patients. Treatment of metastatic breast cancer has become more complex, with regimen selection affected by both inherited germline genetics and somatic changes in the cancer that can evolve over time. The assessment of relevant biomarkers should allow patients to receive the optimal therapies that are most likely to be effective based on the individual characteristics of their cancers. Brittany Harvey: Well, I want to thank you so much for reviewing this guideline with me today, and all of the recommendations and our gaps in evidence, for our listeners. Thank you for your work on this guideline update and thank you for your time today, Dr. Henry. Dr. Lynn Henry: Thank you so much! Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app available on iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.
Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, and Dr. Hope Rugo, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, discuss the practice-changing DESTINY-Breast04 trial as well as novel therapies in metastatic HR+/HER2- breast cancer from the TROPiCS-02 and MAINTAIN studies, all of which were featured at the 2022 ASCO Annual Meeting. TRANSCRIPT Dr. Allison Zibelli: Hello. I'm Dr. Allison Zibelli, your host for the ASCO Daily News Podcast today. I'm a vice-chair and breast medical oncologist at the Sidney Kimmel Cancer Center, Jefferson Health in Philadelphia. My guest today is Dr. Hope Rugo, a professor of medicine and the director of Breast Oncology and Clinical Trials Education at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. We'll be discussing key advances in breast cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes, and disclosures of all guests on the podcasts can be found on our transcripts at asco.org/podcasts. Hope, it's great to talk to you today. Dr. Hope Rugo: Nice to talk to you, too. Dr. Allison Zibelli: Let's begin with perhaps the most exciting abstract at ASCO this year, which was the DESTINY-Breast04 study, that's LBA3, a randomized phase 3 study of trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-low, unresectable and/or metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: Well, of course, this is a hugely practice-changing study as was noted in the second-to-last slide by the discussant [Dr.] Pat LoRusso. So, antibody-drug conjugates are really the next step in delivering chemotherapy to cancer cells. The antibody-drug conjugates allow targeted delivery of a toxin to the cancer cell. I think we didn't understand how important this was going to be. These second, sort of, verging on third-generation antibody-drug conjugates use an antibody approach and to then have a new generation of linkers, which allow the drug to be released locally, but to then have drugs which pack a big bang for the buck. So, the way antibody-drug conjugates are constructed, you need to have a drug that actually can't be given as a naked drug because it's too toxic because you're giving just very small amounts of this drug that are delivered directly to the cancer cell. And the other really critical part of this is that the drug-to-antibody ratio of at least the successful and new antibody-drug conjugates (ADC) is quite high in the 7.5 to 8 toxins per antibody. Now, what that's resulted in is really interesting, is that there's a bystander effect. So, the toxin itself can leak out of the cancer cell that it's targeted and kill neighboring cells, but also because of the construct of these antibody-drug conjugates, what's likely happening is even if the cancer cell's a very low expression of the target, really low, you're able to actually get that ADC into the cancer cell to kill the cancer cell. So that may be a big part of the so-called bystander effect. So trastuzumab deruxtecan is biosimilar trastuzumab linked to a topoisomerase inhibitor deruxtecan, and what happened here was that of course, we saw remarkable data in HER2+ disease, unbelievable p-values in DESTINY-Breast03 compared to T-DM1, a first-generation ADC. But in DESTINY-Breast04, we targeted a population of patients largely with hormone receptor-positive disease who had a little expression of HER2, 1 plus or 2 plus by immunohistochemistry and no gene amplification. And this trial, which randomly assigned patients 2:1 and included just 58 patients with triple-negative disease. So in this trial, 480 had hormone receptor-positive breast cancer, a median of 1 line of prior chemotherapy. They were only allowed up to 2. They were refractory to endocrine therapy, a median of 3 lines of endocrine therapy. In the overall patients and in the hormone receptor-positive patients, there was actually a doubling in progression-free survival (PFS). It started very early, and it continued throughout, and at every landmark analysis, T-DXd was better than the treatment of physician choice that patients were randomly assigned to. It's also important when you're thinking about trials like this to think about what the treatment of physician choice was, and it was all chemotherapy regimens we would use. Paclitaxel, nab-paclitaxel, capecitabine, eribulin, or gemcitabine. And, so, I think that that doesn't bring up any questions. When they looked at the hormone receptor-positive group, they saw, if anything, even a bigger benefit overall. Now, the other endpoint of this trial was overall survival, and at this first analysis, they saw an improvement in overall survival that was quite dramatic. The absolute difference was 6.4 months, which is pretty amazing for an overall survival difference. And then they looked at this exploratory endpoint at the 58 patients who were valuable at triple-negative breast cancer, and then that group of patients, also saw an improvement in PFS of 5.6 months, an improvement in overall survival of 9.9 months, very small group, but amazing data. The forest plots are exactly what you want to see, all the dots line up to the left of 1, and overall responses improved. One of the concerns with this drug has been toxicity. The toxicity showed no new toxicity signals, which is really important. Nausea is the biggest issue that we deal with. It's mostly grade 1 and 2, but still something that's important to manage. A little bit of hair loss, not much in the way of bone marrow suppression, which is interesting. Interstitial lung disease (ILD) or pneumonitis continues to be an important issue to follow. 12% of patients had ILD of any grade. Most of it was grade 1 and 2, but 3 patients died, representing 0.8%. So, this really highlights the importance of monitoring and managing pneumonitis. Regardless of that, few patients had a reduced ejection fraction, but again, very, in general, low grade. This is really a new standard of care, and the standing ovation was really due to the fact that all we do is dedicate ourselves to trying to help patients live longer and better with their cancers, and in this trial, we have a huge win that has no qualifications. We can help patients not only control their disease longer but live longer with T-Dxd compared to standard chemotherapy. Dr. Allison Zibelli: So, Hope, I know as a practicing medical oncologist, I find that our metastatic triple-negative patients are often the biggest therapeutic challenges for us. Will they be doing larger studies with these patients that are HER2-low? Dr. Hope Rugo: It's a really good point. About 65% of patients with hormone receptor-positive disease or so-called HER2-low, centrally confirmed in the study. So, a fair number of people, about a quarter, did not have HER2-low disease when they were tested centrally. In the triple-negative population, who really are ER, PR, HER2- by standard definitions, about a third of the patients might have HER2-low disease. So, there's a lot of interest in further exploring that and looking at the patients who have ultra-HER2-low disease, so between and 1 plus a little bit of expression. That's been studied in the hormone receptor-positive population in DESTINY-Breast06. But there's a lot of interesting further defining that triple-negative population, so to speak, they're going to be triple-negative plus now and understanding what the benefit is in that population. So definitely will be looked at more now moving forward. Dr. Allison Zibelli: Thank you. So, let's move on to Abstract 1002. And the results from the phase 1, 2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate, and patients with HER3 expressing metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: That's a really interesting, another one of these second- to third-generation antibody-drug conjugates. It's just the antibody, instead of being the usual, sort of, HER2 or TROP2 that we're used to thinking about is directed to HER3, 1 of the HER family of proteins. This is interesting. There's actually been a lot of work trying to target HER3 with naked antibodies with disappointing results, although I have to say most of the studies really didn't push it too far. So, with this antibody drug construct, deruxtecan, which is the same as in T-DXd and another TROP2 ADC Dato-DXd is used. So, I will say they do need to change the toxin in the next generation of ADCs. But they looked at, at first did a dose-finding study which has previously been presented, and then a dose expansion in both hormone receptor-positive HER2-negative disease and triple-negative disease. All the triple-negative patients had HER3 high disease by immunohistochemistry, and the hormone-receptor-positive patients were enrolled in 2 cohorts, HER3 high and HER3 low. And the median number of prior treatment regimens that patients had received in the hormone-receptor-positive group was 6 and 2 for the triple-negative group, but there was a huge range, up to 13 lines of treatment. They only had 14 patients with HER2+ disease. So, it's a little bit hard to know what to do with that patient group, but they were heavily pretreated 5.5 prior lines of therapy. The confirmed overall response rate in the 113 patients with combined HER3 high and low was 30%, very impressive, heavily pretreated patients. For triple-negative disease all HER3 high, it was 23%. Again, very nice. And there were 14 patients with HER2+ disease that also were HER3 high. It was about 43%. So those are nice responses, but we always want to know how durable is that. The duration of response ranged from 6 to over 8 months in those 3 different groups. So, these were quite durable. It wasn't any 2- to 3-month duration of response. So very impressive. And then when they looked to see, did it matter whether you had HER3 expression that was high or low in the hormone-receptor positive group, they actually did see responses in the HER3-low group, some very good responses. Overall, there were less patients in that group, but it does suggest that maybe you would still see responses in the HER3-low group, very impressive. And then 1 really interesting correlative study they did was they looked to see what happened to the HER3 expression on the tumor cell over time, and it went down. So, you treated the HER3 expression in most of the patients just dropped off completely, which is really interesting. It didn't have any association with clinical activity, but it's sort of an interesting correlative endpoint. This is a drug that overall was pretty well tolerated. They saw a similar toxicity to T-DXd with a lot of nauseous, a little bit of alopecia, a little bit more bone marrow suppression than we're used to seeing with T-DXd. So, neutropenia was seen in about 10% of patients at the lower dose and about a quarter of the patients at the higher dose. Overall, pretty well tolerated. Now, interstitial lung disease is a toxicity with this construct, and they saw ILD of 7% but most cases were grade 1 and 2. The other interesting toxicity that's unique to this agent is thrombocytopenia. So, they saw a grade 3 or greater rate of thrombocytopenia of 27% in the lower dose group, and in the larger group that received the higher dose, 39% of grade 3 or greater thrombocytopenia, so platelets less than 100,000. Turns out that when you stop the drug, the platelets do come back, so that's a good thing. Sometimes we saw long-term thrombocytopenia with T-DM1. They didn't see bad toxicity like bleeding, but it is something that needs to be managed with this drug because we're not great at managing thrombocytopenia. In any case, it has fast-track designation for another solid tumor, not breast cancer, and we'll have to see where this fits into our dizzying array of very effective ADCs now. Dr. Allison Zibelli: The practicing medical oncologist is not used to testing for HER3 in our patients with breast cancer. How common is it? Dr. Hope Rugo: HER3 expression is quite common in hormone receptor-positive disease, a little less common in triple-negative breast cancer. So, I think that we would see expression if we were going to be treating patients with this particular approach. Dr. Allison Zibelli: All right. Let's move on to Abstract 507, which reported long-term outcomes of adjuvant denosumab in breast cancer, specifically fracture reduction and survival results from 3,425 patients in a randomized double-blind, placebo-controlled ABCSG-18 trial. What are your thoughts about this study? Dr. Hope Rugo: Well, this trial, this is an update of a study that previously has been presented and published, most recent publication was in Lancet Oncology in 2019, and these patients were randomly assigned to receive denosumab at 60 milligrams, important to note the dose, subcutaneously every 6 months versus placebo every 6 months, and they did get placebo subcutaneous injections. And this treatment continued through their endocrine therapy. They showed a dramatic reduction in fracture rate, and that has been maintained over time. We were really surprised enough to suggest that maybe Austrian people didn't go into the sun, so they got more Vitamin D deficiency, hard to know, but the hazard ratio is 0.5. It's unbelievable the number of fractures, 92 for denosumab but 176 for placebo, a P value of less than .0001. So, this is a real endpoint, treating patients who are receiving endocrine therapy that, in this case, non-steroidal aromatase inhibitor therapy that can increase bone loss, have a reduced fracture rate when they received denosumab. So that is the big take-home message, and a medium follow-up of 8 years. But the secondary endpoints included disease-free survival. They had about 20% disease-free survival events and 8% deaths, and what they saw was really interesting. So, the caveat is that 16% of patients were unblinded at the first analysis and half of them got denosumab, so it messed up their results a little bit, but the disease-free survival was significantly better in patients who received denosumab, and the hazard ratio of 0.83 and the hazard ratio does not cross 1. So that's very interesting, and even overall survival, they looked at 2 other endpoints, bone metastasis-free survival, and overall survival. They also trend towards an improvement with a hazard ratio of 0.8 for both of them. And they didn't actually see toxicity. So, patients' brittle bone fractures and osteonecrosis of the jaw (ONJ) are all concerning, but they really just did not see any risks in this patient population. I think there was 1 patient that had what they thought was a brittle bone fracture. Obviously, they watched the mouth very carefully as well. Really dramatic, and I think it's kind of disappointing that we never had any registration approach in this, and also not well-understood why the D-CARE study did not show a benefit, but I think D-CARE was designed differently. This is a better design to focus on our patients and the specific issues, and I think it's intriguing and should be considered as part of our treatment regimen for patients who are at risk for bone loss and have early-stage breast cancer on an aromatase inhibitor. Dr. Allison Zibelli: I've been using DEXA scans and offering denosumab to my patients on AIs that have osteopenia or osteoporosis. Should we be considering it in women with normal bone mass? Dr. Hope Rugo: I think not yet. Unfortunately, this trial was not immediately powered for cancer outcome, although the data are very encouraging. We don't know what the relationship is to bone loss, and providing an environment that's friendlier for cancer cells. So, do you have to have bone loss in order to have the risk that you're reducing with these agents? Certainly, that's what we've seen with zoledronate. So, I think that we don't have sufficient data to use this simply to treat cancer, but I do think that we should be considering this as an agent to give patients who have bone loss, either when you're starting an aromatase inhibitor or during the course of therapy. I think it's well tolerated, and a subcutaneous injection is not difficult. One of the questions that's come up for people is do you get bone loss that increases your risk of fracture after you stop therapy. But clearly from these updated data, these patients were off therapy. They did not have an increase of fractures and the patients treated with denosumab fared much better, I mean the hazard ratio of 0.5. Dr. Allison Zibelli: Let's move on to TROPiCS-02. That's LBA1001. This is a randomized phase 3 study of sacituzumab govitecan versus treatment of physician's choice in patients with hormone receptor-positive, HER2-negative advanced breast cancer. How do you think this study will impact practice? Dr. Hope Rugo: That's a great question. I presented this data, and I think I presented it on a Saturday, and on Sunday we saw the plenary talk of DESTINY-Breast04. These patients enrolled in TROPiCs-02 had a median number of lines of prior chemo 3 with a range of up to 8 actually, compared to a median number of lines as 1 in the DESTINY-Breast04 population. We included all hormone receptor-positive HER2 negative-advanced breast cancer, not centrally confirmed. They included just the HER2 low subset that was centrally confirmed. Everybody in our study had received prior CDK4/6 inhibitors compared to about 70% in DB04. And then 95% of patients in this trial had visceral mets. So, we did really treat a patient population who had very advanced high risk hormone receptor-positive breast cancer. As you know, we saw an improvement and progression-free survival with a hazard ratio of 0.66 meeting the endpoint. We needed a hazard ratio of 0.7, highly statistically significant P value .0003, but the median difference in PFS was only 1.5 months, and overall survival data is not yet mature. So that's brought up the question about how this drug should be used because there was a big fall off in the first 2 months where patients had rapid disease progression with heavily pretreated chemotherapy-resistant disease. We did landmark analyses and there were big separations in PFS at 6, 9, and 12 months, and 12 months, it was 21% patients free of progression and death at 1 year versus 7% for the TPC arm. So, it was a tripling of patients who were free of progression at one year. I think that's clinically relevant. This drug is associated with more neutropenia. That's the primary issue to manage, and probably half of the patients need growth factors at some point. When we looked at other endpoints response to ratio response, etc., we're better with Sacituzumab. So where does this all fit into our treatment paradigm. I think there's the HER2-low patients who will now receive T-DXd up in the, I hope, second line and not in lieu of endocrine therapy, when they're ready for chemo. But there are patients who don't have HER2-low disease and then there are patients who are going to be in the later line setting. So, I do think it still has a place in the treatment department, receptor-positive metastatic breast cancer. The results show that it was better than chemotherapy, physician choice based on our national and international guidelines, and that's better for our patients to have that option. Overall survival data obviously is looked for with great interest and that will help us put this into the right paradigm. And then I also hope that real world data will help us understand how sequential treatment with these different ADCs will benefit our patients. Dr. Allison Zibelli: This is really exciting. Do you think that we're maybe coming toward the end of conventional chemotherapy, especially for women with HER2-positive disease? Dr. Hope Rugo: I wonder if we are. I think we were interested in T-DM1 for HER2-positive disease early on. We've seen some really nice pathologic complete response data as well as adjuvant data in the attempt trial in patients who had stage I disease. Now that we have these second-, third-generation ADCs, T-DXd, I think this could potentially completely replace our chemotherapy. We still have to deal with alopecia. And I will point out ADCs are still chemotherapy. They're just a much more efficient and effective way of delivering treatment, and we need to be very careful to manage the toxicity. Dr. Allison Zibelli: Next, we're going to talk about the main pain trial that's LBA1004, which is a randomized phase 2 trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or hormone receptor-positive HER2-negative metastatic breast cancer, in other words CDK4/6 after CDK4/6. What are your takeaways here? Dr. Hope Rugo: First, just amazing that an investigator-initiated trial could do this well and be placebo-controlled. So, kudos to the principal investigator (PI) [Dr.] Kevin Kalinsky. This trial is a small phase 2 trial. A reasonable number, 119 patients were randomly assigned and evaluable patients could have received up to 1 line of prior chemotherapy for metastatic disease. If you had received prior exemestane, you received fulvestrant, if you received prior fulvestrant, you received exemestane, and actually if you looked at the number of patients who had received fulvestrant, it was 99 versus only 20 with exemestane. So important to keep in mind. If you looked at the overall population where the primary endpoint was progression-free survival, the hazard ratio is 0.57, just median PFS of 2.8 months in patients receiving endocrine therapy and placebo and 5.3 months for patients receiving endocrine therapy and ribociclib. So was this ribociclib after ribociclib or ribociclib after something else. 86% of patients had received palbociclib as their prior CDK4/6 inhibitor, and only about 10% to 14% had received prior ribociclib. So, there's a predominance of palbociclib followed by ribociclib. The other thing that's important to keep in mind is how sick this patient population was. Very few had received prior chemotherapy in the less than 10% range, visceral metastases in about 60%. So that's helpful. Only 19% or so had received 2 or more endocrine therapies from metastases. So, most people did this as their second line treatment. The PFS, when you looked at fulvestrant or exemestane, looked like the benefit was relatively similar, but you know you got 20 patients in the exemestane arm. The hazard ratios, looking at the subgroup analyses, all looked pretty similar, and the overall response and clinical benefit rate were better with continuing the cyclin dependent kinases (CDK) inhibitor. There was interesting sub-analysis looking at mutations and how that affected things. And they looked at patients who had ESR1 mutations or had wild-type ESR1. 42% had ESR1 mutations at study entry, very similar to what we've seen. In that group of patients, remember it's only 33 where they had this analysis, they saw a lot of other mutations. So p53, PIK3CA, FGFR, CCND1—those patients did not benefit. Only 33 patients. No benefit at all, very short PFS, about 3 months. The patients who had ESR1 wild type seemed to benefit a lot, 45 patients going from about 3 months to a little over 8 months. So, this is all hypothesis-generating data. I wouldn't run out and use this as your standard of care now because it is small data. But when the patient doesn't have other good options, I certainly would consider switching the CDK and going on, add that to the next line endocrine therapy. It's important to switch the endocrine therapy. I think we really need to look at the ongoing phase 3 trials to give us better evidence basis and understand the impact of mutations and prior therapy on who might benefit from continued CDK inhibitors after progression on a CDK inhibitor. Dr. Allison Zibelli: I think this is a really exciting trial. We all have a lot of patients on palbociclib and letrozole who've been on for 4, 5 years, and would like to continue with this kind of treatment because the side effects are really manageable. So, I look forward to seeing what's coming in the future with the phase 3 trials. So, let's talk about Abstract 1015, which I thought is a great idea. It looks at the quality of life with ribociclib plus aromatase inhibitor versus abemaciclib plus AI as first-line treatment of hormone receptor-positive, HER2-negative advanced breast cancer, assessed via matching adjusted indirect comparison. Could you tell us what matching adjusted indirect comparison is and why you chose this for the study? Dr. Hope Rugo: It's an interesting question. How do you compare across trials? So, matching this kind of make analysis, we'll call it a make analysis for the purposes of this discussion, allows you to match patients and weight based on their characteristics that might affect patient reported outcomes. And that actually is a way of trying to do a fair cross-trial comparison. So basically, take the study population, you match the inclusion and exclusion criteria, and then you weigh the different criteria so that you can try and make a better association. It's the best way we know of comparing across trials. You know, a lot of people ask why we didn't have PALOMA-2 in here, and that's because they used a different patient reported outcome tool. So, you have to use the same patient reported outcome tool in order to compare. So that's why we did this analysis, and it sort of came on the heels of a survey that Fatima Cardoso presented at San Antonio in 2021, where patients identified diarrhea as a symptom they really didn't like more than everything else. And you can imagine, I think we all have that experience in practice, the unexpected nature of diarrhea and the fact that it does limit your activities and, therefore, quality of life are important. In this analysis, interestingly but not surprisingly, ribociclib favored abemaciclib in diarrhea, and there can be associated appetite loss, so ribociclib also favored abemaciclib for appetite loss. And I thought the last one was interesting—fatigue—because I wouldn't have assumed that fatigue would be different. And maybe it's associated with diarrhea. They have these funny arm symptoms that were better. We don't really know why that was, and it's hard to assess again. We're really not clear based on the differences between the drugs. So, there are limitations to the analysis, but I think that it helps us really in individual patients try and match patients' underlying symptoms with the best treatment to offer them the best quality of life as they're being treated in the metastatic setting. Dr. Allison Zibelli: I thought this study was great because it really centered the experience of the patient and the wishes of the patient. You don't see that designed into many clinical trials, the way this was. So, I thought that was a great feature of this study. Dr. Hope Rugo: I will say that all of the 3 studies that looked at CDK inhibitors, all those 3 studies included patient-reported outcomes. That's an important new approach that is really being focused on. Dr. Allison Zibelli: Do you consider the CDK4/6 inhibitors equivalent in efficacy, and could you substitute them to try to get the side effect profile that you want? Dr. Hope Rugo: Well, I think that we saw in the early stage setting that there are differences. Now, across the different trials, there are big differences in patient populations and inclusions as we saw in the PALOMA-2 results that were presented at ASCO [Annual Meeting], whether the patients had prior chemotherapy like in PALOMA-3, whether they had a short disease-free interval, the higher risk patients in PALOMA-2. The PALOMA trials were more broadly inclusive than the other 2 studies, the MONALEESA and MONARCH series of trials. So, we do have to be a little bit careful about comparing apples to oranges, but we have the early-stage results of MONARCH E showing a clinically important difference in outcome whereas the PALLAS and Penelope-B trials didn't. So that sort of puts us into a little bit of a question period. Are these all patient populations or are there differences between the agents? The PFS and the metastatic setting, all the hazard ratios line up. So, in truth, although I know the activity against cyclin-independent kinases are different between agents, we don't still really understand the clinical differences in efficacy, but I think we all are practicing using evidence-based medicine. I wouldn't, for example, substitute a different CDK4/6 inhibitor for abemaciclib in the treatment of early-stage breast cancer. We have to just learn how to manage the diarrhea and use prophylaxis and dose reduce early to manage this and make it tolerable for our patients. And in the metastatic setting, I think we need to follow evidence-based guidelines and use the best data available to decide on the right treatment approach and sequencing for our patients. Dr. Allison Zibelli: Thank you, Hope, for coming on the podcast today. This was a really interesting review of one of the most exciting ASCO [Annual Meetings] I've been to. And thanks for sharing your valuable insights with us and helping us make sense of all this really new exciting data. We really appreciate it. Dr. Hope Rugo: Thank you. And thank you so much for inviting me. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. That really helps other listeners find us. Thank you. Disclosures: Dr. Allison Zibelli: None disclosed. Dr. Hope Rugo: Honoraria: Puma Biotechnology, Mylan, Samsung Bioepis, Chugai Pharma, Blueprint Medicines Consulting or Advisory Role: Napo Pharmaceuticals Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals, Astellas Pharma, Seattle Genetics, Macrogenics, Boehringer Ingelheim, Polyphor Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)
Listen to a soundcast of the 4/5/2022 FDA approval of Vijoice (alpelisib) for adult and pediatric patients two years of age and older with severe manifestations of PIK3CA-related overgrowth spectrum who require systemic therapy.
Featuring perspectives from Dr Ruth O'Regan, including the following topics: Introduction (0:00) Case: A woman in her late 40s with an ER/PR-positive, HER2-negative, node-negative invasive ductal carcinoma (IDC) — Laila Agrawal, MD (5:09) Case: A woman in her mid-40s with ER/PR-positive, HER2-negative mBC — Raman Sood, MD (22:39) Case: A woman in her early 40s with ER/PR-positive, HER2-negative oligometastatic breast cancer — Arielle Heeke, MD (32:08) Case: A woman in her early 60s with ER/PR-positive, HER2-negative mBC with a PIK3CA mutation — Andrea Stebel, MD (35:31) Case: A postmenopausal woman in her early 50s with Stage IIIB ER/PR-positive, HER2-negative, node-positive breast cancer — Shaachi Gupta, MD, MPH (51:29) Case: A woman in her late 30s with ER/PR-positive, HER2-negative, node-positive IDC with a germline BRCA1 mutation — Dr Agrawal (57:02) CME information and select publications
Neste episódio, Dra. Debora de Melo Gagliato e Dra. Ana Luísa de Castro Baccarin fazem participam de uma discussão com o Dr. Antonio Carlos Buzaid sobre os principais pontos a serem considerados na utilização de alpelisibe na prática clínica. Assista ao Vídeo-MOC completo. mocbrasil.com/blog/videoteca/vol13num03/
Featuring perspectives from Dr Kevin Kalinsky, including the following topics: Introduction (0:00) Journal Club with Dr Kalinsky (1:08) Case: A woman in her mid-60s with ER-positive, PR-negative, HER2-negative metastatic breast cancer (mBC) — Ann Partridge, MD, MPH (17:55) Case: A woman in her early 30s with ER/PR-positive, HER2-negative mBC with a PIK3CA mutation — Arielle Heeke, MD (23:40) Case: A woman in her mid-40s with ER/PR-positive, HER2-negative, node-positive localized breast cancer who had HER2-positive disease after neoadjuvant therapy — Debra Patt, MD, PhD, MBA (30:39) Case: A woman in her early 60s with ER-positive, HER2-negative, node-positive breast cancer — Dhatri Kodali, MD (35:38) Case: A woman in her late 70s with Stage IIIC ER/PR-positive, HER2-negative breast cancer — Rahul Gosain, MD (38:47) Case: A woman in her late 40s with ER/PR-positive, HER2-negative mBC — Ranju Gupta, MD (51:15) San Antonio Breast Cancer Symposium® 2021 Preview (53:51) Beyond the Guidelines (55:57) CME information and select publications
Featuring perspectives from Dr Adam Brufsky, including the following topics: Introduction (0:00) HER2 in the Real World (1:16) Case: A woman in her early 60s with triple-positive metastatic breast cancer (mBC) — Joseph Martins, MD (4:32) Case: A woman in her late 60s with ER/PR-negative, HER2-positive breast cancer and brain metastases — Rohit Gosain, MD (19:41) Case: A woman in her late 60s with ER/PR-positive, HER2-positive mBC with recurrence in the brain — Alan B Astrow, MD (24:49) Journal Club with Dr Brufsky — Part 1 (28:42) Case: A woman in her early 80s with ER-positive, PR-negative, HER2-positive localized breast cancer and treated chronic lymphocytic leukemia — Shachar Peles, MD (31:45) Case: A woman in her late 50s with ER-negative, HER2-positive mBC with a PIK3CA mutation — Sunil Gandhi, MD (45:47) Case: A woman in her early 50s with ER/PR-positive, HER2-positive infiltrating lobular breast cancer — Ferdy Santiago, MD (52:08) Journal Club with Dr Brufsky — Part 2 (55:18) CME information and select publications
Una serie di podcast che ci aggiornano sui dati più importanti nel campo della ricerca e della pratica clinica nel trattamento del tumore della mammella a recettori ormonali positivi e recettori HER2 negativi.Negli ultimi anni infatti l'introduzione dei cosiddetti CDK4/6 inhibitor, ma recentemente anche la disponibilità di farmaci che agiscono sulla pathway di PI3K, in particolare alpelisib che si colloca in combinazione con fulvestrant nel trattamento delle forme con mutazione del gene PIK3CA, hanno cambiato profondamente il paradigma terapeutico in questo setting./p>Seguici sui nostri socialInstagram (@drtalk_it)Twitter (@drtalk_it)YouTube (DrTalk_it)
Una serie di podcast che ci aggiornano sui dati più importanti nel campo della ricerca e della pratica clinica nel trattamento del tumore della mammella a recettori ormonali positivi e recettori HER2 negativi.Negli ultimi anni infatti l'introduzione dei cosiddetti CDK4/6 inhibitor, ma recentemente anche la disponibilità di farmaci che agiscono sulla pathway di PI3K, in particolare alpelisib che si colloca in combinazione con fulvestrant nel trattamento delle forme con mutazione del gene PIK3CA, hanno cambiato profondamente il paradigma terapeutico in questo setting./p>Seguici sui nostri socialInstagram (@drtalk_it)Twitter (@drtalk_it)YouTube (DrTalk_it)
Una serie di podcast che ci aggiornano sui dati più importanti nel campo della ricerca e della pratica clinica nel trattamento del tumore della mammella a recettori ormonali positivi e recettori HER2 negativi.Negli ultimi anni infatti l'introduzione dei cosiddetti CDK4/6 inhibitor, ma recentemente anche la disponibilità di farmaci che agiscono sulla pathway di PI3K, in particolare alpelisib che si colloca in combinazione con fulvestrant nel trattamento delle forme con mutazione del gene PIK3CA, hanno cambiato profondamente il paradigma terapeutico in questo setting./p>Seguici sui nostri socialInstagram (@drtalk_it)Twitter (@drtalk_it)YouTube (DrTalk_it)
Una serie di podcast che ci aggiornano sui dati più importanti nel campo della ricerca e della pratica clinica nel trattamento del tumore della mammella a recettori ormonali positivi e recettori HER2 negativi.Negli ultimi anni infatti l'introduzione dei cosiddetti CDK4/6 inhibitor, ma recentemente anche la disponibilità di farmaci che agiscono sulla pathway di PI3K, in particolare alpelisib che si colloca in combinazione con fulvestrant nel trattamento delle forme con mutazione del gene PIK3CA, hanno cambiato profondamente il paradigma terapeutico in questo setting./p>Seguici sui nostri socialInstagram (@drtalk_it)Twitter (@drtalk_it)YouTube (DrTalk_it)
Una serie di podcast che ci aggiornano sui dati più importanti nel campo della ricerca e della pratica clinica nel trattamento del tumore della mammella a recettori ormonali positivi e recettori HER2 negativi.Negli ultimi anni infatti l'introduzione dei cosiddetti CDK4/6 inhibitor, ma recentemente anche la disponibilità di farmaci che agiscono sulla pathway di PI3K, in particolare alpelisib che si colloca in combinazione con fulvestrant nel trattamento delle forme con mutazione del gene PIK3CA, hanno cambiato profondamente il paradigma terapeutico in questo setting./p>Seguici sui nostri socialInstagram (@drtalk_it)Twitter (@drtalk_it)YouTube (DrTalk_it)
Featuring perspectives from Dr Matthew Goetz, including the following topics: Introduction (0:00) Case: A woman in her late 30s with a 3-cm, weakly ER-positive, PR-negative, HER2-negative, node-positive infiltrating ductal carcinoma (IDC) — Nick C Leasure, MD (22:01) Case: A premenopausal woman in her late 40s with ER/PR-positive, HER2-negative, node-positive IDC — Reshma Mahtani, DO (29:59) Case: A woman in her late 60s with de novo ER/PR-positive, HER2-negative metastatic breast cancer (mBC) — Benjamin Parsons, DO (42:10) Case: A postmenopausal woman in her early 50s with de novo ER/PR-positive, HER2-negative mBC with a PIK3CA mutation — Dr Mahtani (53:50) SABCS 2021 Preview (57:51) CME information and select publications
Featuring perspectives from Drs Jamie Chaft, Solange Peters, Brendan Stiles and Eric Vallieres, including the following topics: Effect of the recent practice-changing data sets in the adjuvant and neoadjuvant treatment of non-small cell lung carcinoma (NSCLC) (0:00) Case: A woman in her late 60s with Stage IIIA squamous cell carcinoma of the lung and a high level of PD-L1 expression (7:46) Strategies to aid shared decision-making in the adjuvant setting for NSCLC (23:43) Potential role of circulating tumor DNA to detect minimal residual disease in the adjuvant and neoadjuvant settings (28:06) Choosing definitive stereotactic radiosurgery versus sublobar resection in patients with NSCLC (34:53) Case: A woman in her early 80s with PD-L1-negative, Stage IIB lung adenocarcinoma with PIK3CA and TP53 mutations and HER2 amplification (37:24) Experiences with surgery after neoadjuvant systemic therapy in NSCLC (55:38) Case: A woman in her mid-70s with localized pulmonary adenocarcinoma with a MET exon 14 skipping mutation (1:06:23) Clinical outcomes from the Phase III CheckMate 816 trial assessing nivolumab in combination with chemotherapy as neoadjuvant therapy for Stage IB-IIIA NSCLC (1:21:36) Case: A 48-year-old man with a 3.1-cm, Stage IB NSCLC with an EGFR exon 19 deletion (1:35:20) Management of oligometastatic disease with surgery and radiation therapy (1:43:32) Numeracy in adjuvant therapy for NSCLC; estimating the benefit to aid patients in therapeutic decision-making (1:49:11) CME information and select publications
Thriving in the Midst of Chaos: Parenting With Special Needs Kids
Episode 113: Lindsay Passodelis' Experience Growing Up With CLOVES Syndrome In this episode, guest Lindsay shares her experience growing up with CLOVES syndrome. CLOVES is a rare overgrowth syndrome with vascular anomalies. Congential lipomatous overgrowth vascular malformation epidermal nevus spinal skeletal anomalies (CLOVES). Everyone has different symptoms, of which there are many. It is caused by a genetic mutation in PIK3CA gene. It is not hereditary. Medical exams would pick up the syndrome. You can also undergo genetic testing to confirm the syndrome. Treatment includes surgery, sclerotherapy, and various medications. Lindsay showed signs of CLOVES at birth. However, they misdiagnosed her as having Protea Syndrome. Once she was finally correctly diagnosed, she was really relieved. Lindsay talks about her experience with CLOVES growing up. She discussed complications, difficulty in daily life with CLOVES, coping, and medication trials. Links: Meet The PROS Comic Book Understanding PROS Instagram Blog Email us if you have any questions or ideas! We are now on instagram! Check out updates on our website. Follow Thriving on Twitter. Check us out on Facebook! We are also on Pinterest! Please subscribe to our podcast in the iTunes store, or wherever you find your podcasts, Leave us a 5-star review, to help us know what you like and what you don't like, and to make sure other like-minded people find support through this podcast. Show Music: Intro Outro: Intro Outro 2 by Mattias Lahoud under CC-BY 3.0 License (www.freesound.org) Theme Song: 90s rock style by monkeyman535 under CC-BY 3.0 License (www.freesound.org) Self Care Song: Green and Orange No Water by Duncan Alex under CC-BY 3.0 License (www.freesound.org) Hosted by: Jessica Temple and Lewis Temple Disclaimer: Our show is not designed to provide listeners with specific or personal legal, medical, or professional services or advice. Parents of children with health issues should always consult their health care provider for medical advice, medication, or treatment. Copyright 2021 Jessica Temple
Researchers are still laying the groundwork in the search for therapeutics that target the mechanism for genetic disorders leading to new treatments. On this month's GenePod, authors of two recently published articles in Genetics in Medicine discuss where trials for such molecules are succeeding and where there is still more research to be done to determine the efficacy and safety of new treatments. Ravi Savairayan, professor of genetics at the Murdoch Children's Research Institute discusses the long-term study of vosoritide – the first drug to be approved to treat achondroplasia in Europe with ongoing FDA review in the United States. Maxime Luu, at the University Hospital of Dijon, explains why a trial to treat PIK3CA overgrowth spectrum (PROS) with the breast cancer drug taselisib was halted and, nevertheless, how this promising line of research may proceed in the future. See acast.com/privacy for privacy and opt-out information.
Featuring perspectives from Dr Kathy D Miller and Ms Kelly Leonard, including the following topics: Introduction: The Practice-Changing Summer of 2021 (0:00) Case 1: A woman in her early 60s with ER-positive, HER2-negative localized breast cancer (13:06) Case 2: A woman in her early 50s with ER-positive, HER2-negative metastatic breast cancer and a PIK3CA tumor mutation (26:46) Case 3: A woman in her early 30s with HER2-positive, ER/PR-positive, node-positive localized breast cancer (34:29) Case 4: A woman in her mid-60s with ER-positive, HER2-positive metastatic breast cancer and brain metastases (39:29) NCPD information and select publications
An interview with Dr. Harold Burstein from Dana Farber Cancer Institute in Boston, MA, chair on “Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: ASCO Guideline Update.” This guideline updates recommendations on use of alpelisib, and the role of biomarkers and CDK4/6 inhibitors. Read the guideline at asco.org/breast-cancer-guidelines. Suggest a topic for guideline development at surveymonkey.com/r/ascoguidelinesurvey. TRANSCRIPT [MUSIC PLAYING] SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcasts.asco.org. My name is Brittany Harvey. And today I'm interviewing Dr. Harold Burstein from Dana-Farber Cancer Institute in Boston, Massachusetts, chair and lead author on endocrine treatment and targeted therapy for hormone receptor-positive HER2 negative metastatic breast cancer ASCO guideline update. Thank you for being here, Dr. Burstein. HAROLD BURSTEIN: Glad to be with you. BRITTANY HARVEY: First I'd like to note that ASCO takes great care in the development of its guidelines in ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Burstein, do you have any relevant disclosures that are related to this guideline topic? HAROLD BURSTEIN: I do not. BRITTANY HARVEY: Great, thank you. Then let's delve into the content of this guideline. So first, what prompted the update of this guideline and what is the focus of this update? HAROLD BURSTEIN: So this guideline focuses on metastatic breast cancer, and in particular, estrogen receptor-positive HER2 negative metastatic breast cancer. Worldwide in 2021, actually breast cancer became the most commonly diagnosed cancer in the world, excepting superficial skin cancers. And so it is a true global health problem. And the most common type of breast cancer is estrogen receptor-positive HER2 negative breast cancer, which accounts for 70% to 75% of all cancer diagnoses in the breast cancer space, and as a consequence, also accounts for 70% to 75% of the cases of metastatic breast cancer. So it's really important from a public health point of view and a quality point of view, both in the United States and globally, to have current up-to-date guidance for the management of this most common form of breast cancer that we have. In addition, there have been several innovations in the way of targeted therapies that are coming into place for advanced ER-positive breast cancer. And increasingly, we are using genomic tests to help us understand how best to treat patients with advanced ER-positive breast cancer. So those two initiatives-- the interest in genomic testing and the use of targeted therapies-- all warranted and justified an update to the guidelines. BRITTANY HARVEY: Great. Thank you for reviewing that landscape of where we are in clinical practice for this guideline. So then I'd like to review the key recommendations that this guideline addresses. So first, should alpelisib be given to post-menopausal women and to male patients with hormone receptor-positive HER2 negative PIK3CA-mutated advanced or metastatic breast cancer? HAROLD BURSTEIN: So alpelisib, as you indicated, is a new drug. It is now FDA approved. And it is a protein kinase targeted inhibitor. And it goes after the PIK3CA-mutated tumors. And in a seminal study called the SOLAR-1 study, there was randomization to endocrine therapy alone with fulvestrant or endocrine therapy plus alpelisib for ER-positive HER2 negative breast cancer. And that study showed two important things. First was that in women whose tumors did not have a PIK3CA mutation, there was no benefit for alpelisib. However, in the women whose tumors did have a PIK3CA mutation, there was an improvement in progression-free survival with the use of this targeted drug alpelisib. So based on that, the guidelines now incorporate alpelisib into the treatment algorithm. And as a corollary, it means that all patients who have ER-positive metastatic breast cancer now need testing of the tumor to see if they have a PIK3CA mutation because that's going to guide therapy. In the guideline, we now suggest that this be a standard thing to do-- to test all tumors for PIK3CA mutation. And in those cases where there is a PIK3CA mutation to add alpelisib-based therapy with endocrine treatment typically in second or subsequent lines of therapy. BRITTANY HARVEY: Great. And thank you for reviewing the evidence base behind that recommendation. So next, what is recommended regarding the role of biomarkers in treatment selection for patients with hormone receptor-positive metastatic breast cancer? HAROLD BURSTEIN: So there are two different ways of thinking about biomarkers. One is traditional biomarkers, such as estrogen receptor, progesterone receptor, and HER2. Those are familiar to all clinicians who have been dealing with breast cancer. The second is to think about some of the newer technologies, including tumor genomic sequencing and the kind of mutational analysis we just discussed with the PIK3CA mutations. So in the breast cancer space, there are some important innovations in that latter genomic or genetic testing. One, of course, is the PIK3CA mutation testing that we now recommend for all cancers. That can be done on the primary tumor, or it can be done on cell-free or circulating tumor DNA samples from the bloodstream in most cases. The other kind of testing we do relates to ESR1 mutations. And one of the reasons that tumors become resistant to aromatase inhibitors is that they acquire mutations in the estrogen receptor itself, so-called ESR1 activating mutations. Those mutations mean that the estrogen receptor is on even in the absence of estrogen. And that accounts for probably 50% to 60% of the resistance that we see in treatment with aromatase inhibitors. So the panel really struggled with this because, on the one hand, this is not a uniformly accepted way to decide how to treat patients. On the other hand, there are a lot of data that women whose tumors have ESR1 mutations get negligible benefit from ongoing use of aromatase inhibitor therapy. So this recommendation fell into sort of our practice suggestions, which is that if you have the information on ESR1, then it probably is the case that there's very little, if any, role for ongoing aromatase inhibitor treatment. This fell short of the highest level in endorsement because, first, it's not a uniformly tested assay. And secondly, it's important to remember that these tumors can still benefit from ongoing anti-estrogen therapy with different anti-estrogens like fulvestrant. And finally, and perhaps this is the most practical issue, the way you become ESR1 mutated is usually through exposure to aromatase inhibitors. And if you've already had a patient with extensive exposure to AIs, and they need ongoing anti-estrogen therapy in the metastatic setting, it usually means you're switching treatment anyway. So that's an example of where we're sort of on the frontier of thinking about dynamic changes in the tumor as a way to select treatment for ER-positive metastatic disease. BRITTANY HARVEY: Great. That's helpful for a clinical interpretation of the recommendations and incorporating these into practice. So the final question that was addressed in this focused update was, what is the role of CDK4/6 inhibitors in the treatment of patients with hormone receptor-positive metastatic breast cancer? HAROLD BURSTEIN: So CDK4/6 inhibitors are another tyrosine kinase inhibitor class of drugs that has really emerged as an important part of first-line therapy for ER-positive metastatic disease. There have been multiple randomized trials looking at either first-line therapy with an aromatase inhibitor with or without a CDKI4/6 inhibitor, or second-line treatment typically with fulvestrant with or without a CDKI4/6 inhibitor in the metastatic setting. And the panel was able to update the guidance here based on the maturation of multiple randomized trials, as well as extensive subset analyses that have been performed by investigators associated with the individual pharmaceutical-led studies and by the FDA itself. So here are some important takeaways. The first is that in long-term follow-up, these drugs as a class are improving overall survival for women with ER-positive HER2 negative metastatic breast cancer. And for that reason, they are a very important part of the standard armamentarium for ER-positive disease. It's important to say that they also delay the onset of need for chemotherapy, and in general, are associated with a very well preserved quality of life. So this is a big win for patients with ER-positive metastatic breast cancer. We typically recommend them in the first-line setting. So if a patient has de novo metastatic disease, then they should get an endocrine therapy such as an aromatase inhibitor with a CDK4/6 inhibitor. If they've previously had adjuvant aromatase inhibitor treatment or recur while on adjuvant endocrine therapy, we often move to fulvestrant plus a CDKI4/6 inhibitor. Both settings have shown substantial benefit for this class of drugs. It's important that clinicians understand the side effects of these drugs. Neutropenia and diarrhea are common side effects associated with the various drugs. And because of the prevalence of ER-positive metastatic disease, it's really important for clinicians and all those who care for advanced breast cancer patients to know how to manage those side effects carefully. The panel discussed controversial issues, I suppose you might say, in the management. What about patients who have truly minimal metastatic disease? There aren't a lot of data on how best to think about those patients. And we all can imagine on a case-by-case basis an individual who might not need a CDK4/6 inhibitor at a given moment in time. But what was impressive when we pulled all the data was that in subset analyses, it's really hard to find a group of patients that does not benefit from the incorporation of these drugs. So that included premenopausal women who also get concurrent ovarian suppression and then endocrine therapy plus the CDK4/6 inhibitor. It included women with bone-only metastatic disease. It included women whose tumors were ER-positive but PR negative, or had other variations in ER expression. It included patients who had less rather than more metastatic cancer, including visceral disease. So in the literature, one is hard-pressed to see a subset that does not benefit meaningfully from this class of drugs. So we really wanted to reiterate in the algorithms just how important these are. They should be the standard first-line treatment for metastatic disease either paired with an AI or with fulvestrant. And so one of the other nice things that the update gave us was the opportunity to put in some fresh sort of algorithm flow sheets. I would very much encourage people to look at that. They make fantastic PowerPoint or downloadable Twitter documents if you are so inclined. But it's very clear the way the treatment should flow, which is the initial therapy is endocrine treatment plus a CDK4/6 inhibitor. While the patients are getting that, we typically test for PIK3CA mutations. In second line, if it's a PIK3CA mutated, you have the option of using alpelisib. You also might consider an older drug for PIK3CA wild type tumors called everolimus. We reiterated that recommendation in the guideline. Finally, one more thing to touch on that is emerging in the guidelines we generated and in the parallel guideline process for the ASCO guidance on chemotherapy-resistant or refractory breast cancer is the importance of genetic testing all patients who have metastatic breast cancer to look for the possibility of a BRCA1 or BRCA2 deleterious mutation, because there now is FDA approval for PARP inhibitors in the setting of metastatic disease. And one of the interesting things is that as we test more and more, we're seeing that not all the patients who are found to have a BRCA1 or 2 mutation meet the classic criteria for genetic testing-- strong family history, or say, triple-negative breast cancer. So it's really important to test, because that class of drugs, the PARP inhibitors, can be immensely helpful in women with ER-positive metastatic disease when they harbor a BRCA1 or 2 mutation. One of the things the guideline panel wrestled with and ended up putting into the sort of clinical discussion, as opposed to the strong guidance, was the 1% of patients who have PALB2 mutations. So PALB2 mutation, another hereditary predisposing factor for breast cancer. Most tumors that arise in PALB2 mutation carriers are in fact estrogen receptor positive. And a very small study, now published in the JCO, has suggested that those patients have a very high likelihood of response to PARP inhibitors. Because there were only like 15 patients in that cohort, we didn't feel that this warranted clear endorsement in the guidelines. But at the same time, everyone on the panel acknowledges that this is an active drug in that rare subset of tumors with PALB2 mutations in addition to the BRCA1 or 2 mutations. So the takeaway here is that genetic testing should be standard for all patients with advanced metastatic breast cancer to see if the patient is a candidate for a PARP inhibitor-based therapy. BRITTANY HARVEY: Definitely. Well, thank you for reviewing all of those updated recommendations and highlighting some of the ones that were still relevant to this guideline. HAROLD BURSTEIN: Work in progress. BRITTANY HARVEY: Yeah, definitely. And then finally, what is the importance of this guideline update? And how will it impact both clinical practice and what does it mean for patients? HAROLD BURSTEIN: Well, I think guidelines like this have multiple purposes. The first is to sort of describe the state of the art. And while breast cancer is a very common disease, and most clinicians who take care of a lot of cancer patients will see a lot of advanced breast cancer, I think it's still helpful to articulate the rationale for these treatment recommendations. And one of the great things about the ASCO guideline process is the thoroughness of the literature review, the thoroughness of the search to make sure we're including all important publications, and the thoughtfulness that the panel, which includes experts, patient advocates, quality of life expertise, all those things bring to bear on really thinking through what makes sense and what does not for our patients based on the best science available. So I think it is an important activity to really sort of benchmark where we're at. The second thing we've tried to do in the guideline is to introduce areas of nuanced discussion, because not every patient is the same. And I think for those who are interested and take the time to read the guideline, there really is a very nice discussion about how our panel thought about when best to use this approach and when to use a different approach. Third, there's extensive discussion of the side effects and the appropriate management of the side effects. These are drugs that do carry risks. And while by oncology standards, many of them are, quote, "well tolerated," unquote, there's no doubt that there are side effects to these drugs. And it's important for clinical teams to know how to manage them. Finally, I think by putting forward all the evidence, you make clear to investigators, to drug companies, to patients and advocates, and others who are involved in the review of new drugs what the benchmarks are and what the criteria should be for designing clinical trials and for approving new drugs. And I think we've done a nice job of framing that discussion quite handsomely in this guideline and to all of the ASCO guidelines. BRITTANY HARVEY: Great. Well, thank you so much for your work on this guideline update and for taking the time to speak with me today, Dr. Burstein. HAROLD BURSTEIN: Happy to join you and thanks very much. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/breast cancer guidelines. Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at SurveyMonkey.com /r/ascoguidelinesurvey. The link is also available in the episode notes of this podcast. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]
Featuring an interview with Dr Sara M Tolaney, including the following topics: Role of the Breast Cancer Index® in predicting benefit from extended aromatase inhibitor therapy for hormone receptor (HR)-positive breast cancer (0:00) ADAPT HR-positive/HER2-negative trial: Prognostic utility of genomic assays, clinical factors and response to endocrine therapy for patients with high-risk luminal breast cancer (5:43) De-escalation of neoadjuvant chemotherapy in the treatment of early breast cancer — Clinical outcomes from the ADAPT HR-negative/HER2-positive trial (9:49) Effect of dose escalation on the tolerability of neratinib — Results from the CONTROL study (15:02) Phase II GeparNuevo study: Addition of durvalumab to neoadjuvant anthracycline/taxane therapy for early triple-negative breast cancer (17:13) Neoadjuvant talazoparib for patients with HER2-negative early breast cancer with germline BRCA1/2 mutations — Results from the Phase II NEOTALA study (21:53) Results from the Phase III OlympiA trial assessing adjuvant olaparib for patients with high-risk HER2-negative early breast cancer with germline BRCA1/2 mutations (23:02) Updated survival results from Phase III studies of CDK4/6 inhibitors in combination with hormonal therapy for HR-positive, HER2-negative advanced breast cancer (27:23) Long-term outcomes with alpelisib and fulvestrant for patients with HR-positive advanced breast cancer with PIK3CA mutations (30:58) Trastuzumab with endocrine therapy or chemotherapy as first-line treatment for HR-positive, HER2-positive metastatic breast cancer: Results from the SYSUCC-002 trial (33:20) Subgroup analysis of the DESTINY-Breast01 trial: Efficacy and safety of trastuzumab deruxtecan in patients with HER2-positive breast cancer and stable brain metastases (36:29) BEGONIA: A Phase Ib/II study of durvalumab combinations for advanced triple-negative breast cancer (39:49) CME information and select publications
Mandy Sellars is the Chairperson of GoPI3Ks charity, which is focused on people with PIK3CA related overgrowth spectrum (PROS), an umbrella term for a group of very rare syndromes characterized by malformations and tissue overgrowth, caused by somatic mutations in PIK3CA gene. PIK3CA stands for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic sub-unit alpha, a gene that encodes a lipid kinase involved in multiple signaling pathways, influencing cellular functions such as growth, death, and proliferation. Ms. Sellars herself also possesses a very rare form of this genetic mutation that has resulted in extraordinary growth in both of her legs, but in PROS diseases individual malformations are seen in several different tissues such as skin, vasculature, bone, fat and brain tissue, depending on the specific disease. Ms. Sellars obtained a B.Sc. in Psychology from the University of Central Lancashire and has become a patient advocate, fundraiser for care and research, as well as a reality star along the way.
VIDEOS 1. Sen. Johnson and Dr. Pierre Kory on the impact of censorship in fight against COVID-19 2. New Rule: Getting It in the Nuts | Real Time with Bill Maher (HBO) 3. Black father destroys critical race theory at school board meeting 4. Wuhan 15,00 bat samples and their virus databases all wiped from the internet 5. Fauci, Gain-of-Function Research, and Wuhan Lab Funding. Joe Rogan with Krystal Ball & Saagar Enjeti Krystal Ball and Sagaar Enjeti are political commentators and hosts of the YouTube show and podcast "Breaking Points". CoQ10 supplementation associated with lower pro-inflammatory factors in randomized trial Shahid Sadoughi University of Medical Sciences (Iran), June 8 2021 A double-blind trial reported in the International Journal of Vitamin and Nutrition Research found a reduction in markers ofinflammation in mildly hypertensive patients given coenzyme Q10 (CoQ10) for twelve weeks. Participants who received CoQ10 also experienced an increase in adiponectin: a protein secreted by adipose tissue that has an anti-inflammatory effect and which has been found to be reduced in high blood pressure and cardiovascular disease. "Considering that coenzyme Q10 has attracted noticeable attention in recent years for the treatment of cardiovascular diseases and hypertension in regard to its effect on inflammatory factors such as cytokines, it is therefore hypothesized that supplementation with coenzyme Q10 reduces the proinflammatory factors," write Nasim Bagheri Nesami of Iran's Shahid Sadoughi University of Medical Sciences and colleagues. "This study was conducted in order to determine the effects of coenzyme Q10 on proinflammatory factors as well as on adiponectin in patients with mild hypertension." Sixty men and women were randomized to receive 100 milligrams CoQ10 or a placebo for a twelve week period. Plasma adiponectin, high-sensitivity C-reactive protein (hs-CRP, a marker of inflammation) and the cytokines interleukin 2, interleukin 6 and tumor necrosis factor-alpha were measured before and after treatment. At the end of the study, participants who received CoQ10 had significant declines in interleukin-6 and hs-CRP compared with levels measured upon enrollment. They also experienced an increase in adiponectin, while levels in the placebo group slightly declined. The authors suggest that CoQ10 could be prescribed as a supplement along with antihypertensive medication for patients with mildly elevated blood pressure, and recommend that further research be conducted to validate the current findings. Exposure to nature during COVID-19 lockdown was beneficial for mental health A study by the ICTA-UAB and the University of Porto analyses the effects of exposure to green spaces during the first months of the COVID19 pandemic in Spain and Portugal Universitat Autònoma of Barcelona (Spain), June 18, 2021 A study carried out by the Institute of Environmental Science and Technology of the Universitat Autònoma de Barcelona (ICTA-UAB) and the Instituto de Saúde Pública of the University of Porto (ISPUP), concludes that exposure to natural spaces during the first COVID-19 lockdown in 2020 was beneficial for the mental health of Spanish and Portuguese citizens. The research shows that, in Portugal, during the first confinement, people who maintained or increased contact with natural public spaces, such as parks and coastal areas, or who could contemplate these spaces from their homes, presented lower levels of stress, psychological distress and psychosomatic symptoms. In Spain, those who maintained or increased contact with private natural spaces, such as indoor plants or community green areas, presented lower levels of stress and psychosomatic symptoms. This could be due to the fact that Spain adopted more restrictive measures for foreign circulation during the period analysed. The research Exposure to nature and mental health outcomes during COVID-19 lockdown. A comparison between Portugal and Spain, published in the journal Environment International, was conducted between March and May 2020. Dr Ana Isabel Ribeiro, researcher at the ISPUP and first author of the work together with Margarita Triguero-Mas from the ICTA-UAB says that "we decided to study whether natural, public and private spaces had a beneficial effect on the mental health of Portuguese and Spanish citizens, helping them to better cope with the negative effects of lockdown". For her part, Margarita Triguero-Mas adds that "people around us and ourselves talked about how we missed the park we crossed when we went to the office or the walk on the beach with our dogs, so we wanted to check to what extent contact with natural spaces was an important factor during confinement". Several previous articles have also shown the positive impact of exposure to natural spaces on mental health, that is, in reducing stress, anxiety and improving psychological well-being as a whole. "Taking into account what is described in the literature, we wanted to evaluate whether people who enjoyed greater exposure to natural spaces during the first COVID-19 lockdown had better mental health indicators than those who had no contact with natural areas", explains Dr Ribeiro. At the same time, they wanted to investigate whether exposure to private natural spaces, such as gardens, orchards or plants, was more beneficial among Spanish citizens than among Portuguese, given that Spain applied stricter measures to restrict mobility than Portugal. To carry out the research, the authors applied an online questionnaire, between March 27 and May 6, 2020, aimed at all citizens aged 18 years old or older, residing in Spain or Portugal. The survey covered aspects related to the frequency and type of exposure people had to natural spaces (public and private), before and during the first confinement; mental health questions to assess levels of stress, mental disorders and somatization symptoms, and sociodemographic issues. Of the more than 3,000 citizens (n = 3,157) who answered the questionnaire, 1,638 were Portuguese and 1,519 Spanish. In both countries, during the confinement, there was a significant reduction in the use of public natural spaces, such as beaches, parks and gardens, and an increase in contact with private natural spaces, such as community gardens, urban gardens and plants, especially in Spain. People living in single-family houses (detached house) and flats located in cities were the ones who least maintained or increased their exposure to public natural spaces in both countries. In Spain, where the measures during the period analysed were much more restrictive and it was forbidden to leave the house and public outdoor spaces were closed, the benefits of exposure to public natural spaces were not as relevant as in Portugal, but it was clear the importance of private natural elements. Among the Spanish citizens who participated in the study, 66% decreased the frequency of exposure to public natural spaces (compared to 54% in Portugal). In Spain, people who had the opportunity to continue dedicating or increasing the time dedicated to caring for their plants had lower stress levels, while those who were able to continue enjoying or increasing the time of use of community green spaces had lower rates of somatization. In Spain, it is remarkable that the people who least maintained or increased the care of indoor plants were people over 65 years of age, those who lived with several people at home or those who were in a second residence during confinement. In contrast, the people who maintained or increased the care of indoor plants the most were those with children, but without dependent adults. In Portugal, those who were confined the longest and those who commuted to work were those who least maintained or increased their contact with the natural public spaces. In turn, those who practiced physical exercise indicated greater exposure to these places. Portuguese citizens who managed to maintain or increase their exposure to natural public spaces showed lower levels of stress compared to those who did not. Likewise, those who contemplated natural spaces from their homes obtained improvements in all the mental health outcomes analysed: stress, mental disorders and somatization. "This study clearly demonstrates the benefit of natural spaces for the mental health of the population in a context of public health crisis," says Ana Isabel Ribeiro. "Public authorities and decision-makers could implement measures that facilitate access to natural public spaces, in a safe and controlled manner, in the context of a pandemic. This is particularly important for the most socially and economically vulnerable population groups, and for those who have little access to these spaces in their private context", she emphasizes. In addition, Dr Triguero-Mas adds that "our study is especially important for cities like Barcelona, where new buildings rarely have balconies or community spaces with vegetation. It is important to revalue how building remodelling or new homes can be healthier spaces that promote and prevent deterioration in the health of the people who inhabit them". Flame retardants and pesticides overtake heavy metals as biggest contributors to IQ loss New York University, June 2, 2021 Adverse outcomes from childhood exposures to lead and mercury are on the decline in the United States, likely due to decades of restrictions on the use of heavy metals, a new study finds. Despite decreasing levels, exposure to these and other toxic chemicals, especially flame retardants and pesticides, still resulted in more than a million cases of intellectual disability in the United States between 2001 and 2016. Furthermore, as the target of significantly fewer restrictions, experts say, flame retardants and pesticides now represent the bulk of that cognitive loss. NYU Grossman School of Medicine researchers found that IQ loss from the toxic chemicals analyzed in their study dropped from 27 million IQ points in 2001 and 2002 to 9 million IQ points in 2015 and 2016. While this overall decline is promising, the researchers say, their findings also identify a concerning shift in which chemicals represent the greatest risk. Among toxin-exposed children, the researchers found that the proportion of cognitive loss that results from exposure to chemicals used in flame retardants, called polybrominated diphenyl ethers (PDBEs), and organophosphate pesticides increased from 67 percent to 81 percent during the same study period. "Our findings suggest that our efforts to reduce exposure to heavy metals are paying off, but that toxic exposures in general continue to represent a formidable risk to Americans' physical, mental, and economic health," says lead study investigator Abigail Gaylord, MPH, a doctoral candidate in the Department of Population Health at NYU Langone. "Unfortunately, the minimal policies in place to eliminate pesticides and flame retardants are clearly not enough." The substances analyzed are found in household products from furniture upholstery to tuna fish, and can build up in the body to damage organs, researchers say. Heavy metals, lead and mercury in particular, are known to disrupt brain and kidney function. In addition, they, along with flame retardants and pesticides, can interfere with the thyroid, which secretes brain-developing hormones. Experts say exposure at a young age to any of these toxins can cause learning disabilities, autism, and behavioral issues. In their investigation, the researchers found that everyday contact with these substances during the 16-year study period resulted in roughly 1,190,230 children affected with some form of intellectual disability. Overall childhood exposures cost the nation $7.5 trillion in lost economic productivity and other societal costs. "Although people argue against costly regulations, unrestricted use of these chemicals is far more expensive in the long run, with American children bearing the largest burden," says senior study author Leonardo Trasande, MD, MPP, the Jim G. Hendrick, MD Professor at NYU Langone Health. Publishing online Jan. 14 in the journal Molecular and Cellular Endocrinology, the new study is the only long-term neurological and economic investigation of its kind, the authors say. The investigators analyzed PBDE, organophosphate, lead, and methylmercury exposures in blood samples from women of childbearing age and 5-year-olds. Data on women and children was obtained from the National Health and Nutrition Examination Survey. The researchers used results from several previous environmental health studies to estimate the annual number of IQ points lost per unit of exposure to each of the four main chemicals in the study. Then, they estimated the lost productivity and medical costs over the course of the children's lives linked to long-term intellectual disability using a second algorithm, which valued each lost IQ point at $22,268 and each case of intellectual disability at $1,272,470. While exposure to these chemicals persists despite tightened regulations, experts say Americans can help limit some of the effects by avoiding the use of household products or foods that contain them. "Frequently opening windows to let persistent chemicals found in furniture, electronics, and carpeting escape, and eating certified organic produce can reduce exposure to these toxins," says Trasande, who also serves as chief of environmental pediatrics in the Department of Pediatrics at NYU Langone. Trasande notes that the impact of these chemicals may be worse than their study can capture since there are far more hazards that affect brain development than the four highlighted in the investigation, and other potential consequences beyond IQ loss. "All the more reason we need closer federal monitoring of these substances," she says. The study authors say they plan to explore the cost of exposure to endocrine-disrupting chemicals in other countries. Red meat consumption may promote DNA damage-assoc. mutation in colorectal cancer patients Study provides mechanistic link between red meat consumption and colorectal cancer development Harvard Medical School, June 17, 2021 Bottom Line: Genetic mutations indicative of DNA damage were associated with high red meat consumption and increased cancer-related mortality in patients with colorectal cancer. Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research Author: Marios Giannakis, MD, PhD, an assistant professor of medicine at Harvard Medical School and a physician at Dana-Farber Cancer Institute Background: "We have known for some time that consumption of processed meat and red meat is a risk factor for colorectal cancer," said Giannakis. The International Agency for Research on Cancer declared that processed meat was carcinogenic and that red meat was probably carcinogenic to humans in 2015. Experiments in preclinical models have suggested that red meat consumption may promote the formation of carcinogenic compounds in the colon, but a direct molecular link to colorectal cancer development in patients has not been shown, Giannakis explained. "What is missing is a demonstration that colorectal cancers from patients have a specific pattern of mutations that can be attributed to red meat," he said. "Identifying these molecular changes in colon cells that can cause cancer would not only support the role of red meat in colorectal cancer development but would also provide novel avenues for cancer prevention and treatment." How the Study was Conducted: To identify genetic changes associated with red meat intake, Giannakis and colleagues sequenced DNA from matched normal and colorectal tumor tissues from 900 patients with colorectal cancer who had participated in one of three nationwide prospective cohort studies, namely the Nurses' Health Studies and the Health Professionals Follow-Up Study. All patients had previously provided information on their diets, lifestyles, and other factors over the course of several years prior to their colorectal cancer diagnoses. Results: Analysis of DNA sequencing data revealed the presence of several mutational signatures in normal and cancerous colon tissue, including a signature indicative of alkylation, a form of DNA damage. The alkylating signature was significantly associated with pre-diagnosis intake of processed or unprocessed red meat, but not with pre-diagnosis intake of poultry or fish or with other lifestyle factors. Red meat consumption was not associated with any of the other mutational signatures identified in this study. In line with prior studies linking red meat consumption with cancer incidence in the distal colon, Giannakis and colleagues found that normal and cancerous tissue from the distal colon had significantly higher alkylating damage than tissue from the proximal colon. Using a predictive model, the researchers identified the KRAS and PIK3CA genes as potential targets of alkylation-induced mutation. Consistent with this prediction, they found that colorectal tumors harboring KRAS G12D, KRAS G13D, or PIK3CA E545K driver mutations, which are commonly observed in colorectal cancer, had greater enrichment of the alkylating signature compared to tumors without these mutations. The alkylating signature was also associated with patient survival: Patients whose tumors had the highest levels of alkylating damage had a 47 percent greater risk of colorectal cancer-specific death compared to patients with lower levels of damage. Author's Comments: "Our study identified for the first time an alkylating mutational signature in colon cells and linked it to red meat consumption and cancer driver mutations," said Giannakis. "These findings suggest that red meat consumption may cause alkylating damage that leads to cancer-causing mutations in KRAS and PIK3CA, thereby promoting colorectal cancer development. Our data further support red meat intake as a risk factor for colorectal cancer and also provide opportunities to prevent, detect, and treat this disease." Giannakis explained that if physicians could identify individuals who are genetically predisposed to accumulating alkylating damage, these individuals could be counseled to limit red meat intake as a form of precision prevention. In addition, the alkylating mutational signature could be used as a biomarker to identify patients at greater risk of developing colorectal cancer or to detect cancer at an early stage. Because of its association with patient survival, the alkylating signature may also have potential as a prognostic biomarker. However, future studies are needed to explore these possibilities, Giannakis noted. Study Limitations: A limitation of the study is the potential selection bias of study participants, as tissue specimens could not be retrieved from all incident colorectal cancer cases in the cohort studies. Current studies from Giannakis and his colleagues are exploring the potential role of red meat intake and alkylating damage in diverse groups of patients. Funding & Disclosures: The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (co-administered by the AACR), the Project P Fund, the Cancer Research UK Grand Challenge Award, the Nodal Award from the Dana-Farber Harvard Cancer Center, the Friends of the Dana-Farber Cancer Institute, the Bennett Family Fund, and the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance and Stand Up To Cancer. Giannakis has received research funding from Bristol-Myers Squibb, Merck, Servier, and Janssen unrelated to this study. Association of higher average daily polyphenol intake with Mediterranean diet adherence and decreased waist to hip circumference University of the Aegean (Greece), June 14, 2021 According to news reporting originating from the University of the Aegean research stated, “Research data indicate the possible effect of both polyphenols consumption and Mediterranean diet adherence on metabolic diseases' prevalence. The present retrospective study investigated the possible association of polyphenols mean daily intake with Mediterranean diet adherence and anthropometric indices in a sample of the Greek population.” Our news reporters obtained a quote from the research from University of the Aegean: “A total of 250 healthy volunteers, aged between 18 and 65 years, were randomly recruited from central and northern Greece. Total daily polyphenols intake was estimated using a semi-quantitative food frequency questionnaire (FFQ) based on the NHANES study, while Med Diet Score was used for the degree of Mediterranean diet adoption. Daily polyphenols intake was identified by the Phenol Explorer database, and anthropometric measurements (BMI, waist-to-hip circumference, and body composition) were performed. The mean daily polyphenols intake was determined to be 1905 mg, while most of the participants had moderate or high mean consumption last year (67.5% of the sample were consuming more than 1000 mg/d). Moderate adherence to the Mediterranean diet (higher Med Diet Score) was associated with increased mean daily polyphenols intake (* * p* * = 0.016). Increased polyphenols intake and higher Med Diet Score were associated with decreased waist-to-hip circumference (* * p* * = 0.027, 0.004, respectively).” According to the news editors, the research concluded: “Specific functional foods rich in polyphenols, such as sour cherry, tomatoes, black tea, and cocoa were associated with improved body composition indices. Larger epidemiological studies need to be performed for safer conclusions about whole population polyphenols intake and its association with metabolic disease biomarkers.” Whole, natural fiber works best to protect gut mucosal layer, researcher says University of Michigan, June 12, 2021 Dietary fiber plays an important role in protecting the gut's mucosal layer, according to research presented at the recent Probiota Americas event. It has long been known that the gut stays healthier and performs better with adequate fiber. But why? This is one of the questions that informed the research conducted by Dr Eric Martens, assistant professor of microbiology and immunology at the University of Michigan. Martens presented his research at the IPA World Congress + Probiota Americas event, which was hosted by William Reed in Chicago last week. The event brought together 280 regulators, probiotics and prebiotics researchers and product developers. Protecting the mucosal layer Martens said that his research showed that without adequate fiber in the gut, some organisms that might be nourished by that food source will look to alternative sources, one of which is the gut's mucosal layer. That layer is a critical component of the gut wall, and when it is eroded or absent harmful bacteria have an opportunity to latch onto the cells of the wall itself. “The core of our research is we are interested in the physiology of the many bacteria that live in the gut and defining at the functional and mechanistic level how they work with goal of understanding how the community works,” Martens said. The study he presented used 14 different bacteria with defined characteristics in a mouse model. The study had three groups, a group fed a fiber free diet, one with a whole grain diet rich in natural fibers, and a third that had fiber added back in in the form of purified, prebiotic fibers. His research found that the whole grain, natural fibers fostered a microbial community in which the muscosa-eroding organisms were suppressed the best. He postulated that this could be because the large, whole food particles typical of the natural fiber diet were best able to reach the distal regions of the gut and affect the microbial community makeup there, whereas the purified fibers may have been mostly digested by that point. What Is the Liver Powerhouse Silymarin? GreenMedInfo June 17th 2021 Here's what science has found most beneficial about silymarin, extracted from milk thistle and known to be a friend of your liver mainly through its antioxidant and anti-inflammatory properties When it comes to treating liver and gallbladder disorders, there is one name that stands out: silymarin. As a group of flavonolignans extracted from milk thistle, silymarin has been traditionally used for various protective benefits, from reinvigorating liver function to promoting breast milk production. The milk thistle plant, scientifically known as Silybum marianum, is a prickly plant with purple flowers and milky white veins present on the leaves, thus its name. Silymarin is the group of plant compounds that act as its active ingredient.[i] Silymarin is the main bioactive component of this medicinal plant. It is a mix of various flavonolignans, includings silybinin A and B, isosilybinin A and B, silychristin and silydianin.[ii] Milk thistle extract has a high silymarin content of approximately 65% to 80%. Silymarin is famed for its antioxidant, antiviral and anti-inflammatory components,[iii] as well as its traditional use or treating the liver and restoring its health. In addition, milk thistle itself is generally considered safe to take. Side effects are rare, and in an oral form standardized to contain 70% to 80% silymarin, it appears to be safe for up to 41 months of use.[iv] Silymarin's Liver-Protective Effects Fights liver inflammation and liver damage. Mounting evidence shows improvements in liver function among people with liver diseases who have taken a milk thistle supplement.[v] This suggests protection against flavanone silibinin liver inflammation and liver damage through use of the natural -- silymarin's primary active component -- which was combined with phosphatidylcholine in a specific study to enhance its solubility and bioavailability. Protects from toxins such as amatoxin, produced by Amanita mushroom, which can cause death if ingested. Two cases in the U.S. were treated with N-acetylcysteine, high-dose penicillin, cimetidine and silibinin.[vi] Uncontrolled trials and case reports cited successful treatment with intravenous silibinin, a flavonolignan isolated from milk thistle extracts, in nearly 1,500 cases.[vii] Overall mortality in those treated with the formula was less than 10%, compared to more than 20%when using penicillin, or a mix of silibinin and penicillin. Reduces liver fibrosis. In a randomized trial of 99 patients, the team administered silymarin in 700-milligram (mg) doses, or a placebo, given three times daily for 48 weeks.[viii] Non-alcoholic fatty liver disease (NAFLD) activity score was reduced by 32.7% in the silymarin group compared to 26% in the placebo group. Among the secondary outcomes were reductions in inflammation and fibrosis score in the silymarin group, leading the researchers to conclude that silymarin may decrease liver fibrosis, to be confirmed in larger trials. Fibrosis is the formation of abnormally large amounts of scar tissue in the liver. Helps prevent liver cancer. Studies have concluded that the long-term use of silymarin significantly increases survival time among patients with alcohol-induced liver cirrhosis, a risk factor for liver cancer. Silymarin can also significantly reduce tumor cell proliferation, angiogenesis or new blood vessel formation, as well as insulin resistance.[ix] The chemopreventive effects "have been established in several studies using in vitro and in vivo methods," according to the researchers, and combine well with anti-inflammatory and inhibitory effects on the metastasis or spread of cancer. Contributes to liver regeneration. An animal study suggested that silymarin played a crucial role in accelerating liver regeneration after liver resection, a kind of surgery designed to remove cancerous tumors from the liver.[x] Liver regeneration is thought to evolve to protect animals from loss of liver due to toxins or tissue injury. Silymarin for Breastfeeding, Neurological Support Not to be ignored is silymarin's formidable list of other health benefits, such as boosting milk production in lactating mothers. A randomized trial found that mothers taking 420 mg of silymarin for 63 days produced more breast milk than subjects who took a placebo.[xi] Silymarin combined with phosphatidylserine and galega also increased milk production in moms of preterm infants, without any significant side effects.[xii] Milk thistle is also a traditional remedy for neurological disorders such as Alzheimer'sand Parkinson's diseases. Its antioxidant and anti-inflammatory action mean it may be neuroprotective and help prevent the brain decline experienced with aging.
Una serie di podcast che ci aggiornano sui dati più importanti nel campo della ricerca e della pratica clinica nel trattamento del tumore della mammella a recettori ormonali positivi e recettori HER2 negativi. Negli ultimi anni infatti l'introduzione dei cosiddetti CDK4/6 inhibitor, ma recentemente anche la disponibilità di farmaci che agiscono sulla pathway di PI3K, in particolare alpelisib che si colloca in combinazione con fulvestrant nel trattamento delle forme con mutazione del gene PIK3CA, hanno cambiato profondamente il paradigma terapeutico in questo setting.Seguici sui nostri socialInstagram (@drtalk_it)Twitter (@drtalk_it)YouTube (DrTalk_it)
Una serie di podcast che ci aggiornano sui dati più importanti nel campo della ricerca e della pratica clinica nel trattamento del tumore della mammella a recettori ormonali positivi e recettori HER2 negativi. Negli ultimi anni infatti l'introduzione dei cosiddetti CDK4/6 inhibitor, ma recentemente anche la disponibilità di farmaci che agiscono sulla pathway di PI3K, in particolare alpelisib che si colloca in combinazione con fulvestrant nel trattamento delle forme con mutazione del gene PIK3CA, hanno cambiato profondamente il paradigma terapeutico in questo setting.Seguici sui nostri socialInstagram (@drtalk_it)Twitter (@drtalk_it)YouTube (DrTalk_it)
Proceedings from the first in a series of 11 integrated webinars held in association with the 2021 ONS Annual Congress. Featuring perspectives from Drs Carey K Anders, Kathy D Miller and Sara M Tolaney on cases from the practices of Ms Gretchen Santos Fulgencio, Ms Allie Hershey and Ms Kelly Leonard, including the following topics: Introduction (0:00) Management of Estrogen Receptor (ER)-Positive Breast Cancer (9:58) Case: A woman in her early 30s with localized ER/progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and 3 positive nodes — Gretchen Santos Fulgencio, MSN, FNP-BC (10:31) Case: A woman in her early 50s with ER-positive, HER2-negative metastatic breast cancer and a PIK3CA tumor mutation — Kelly Leonard, MSN, FNP-BC (31:34) Treatment of HER2-Positive Breast Cancer (41:14) Case: A woman in her early 30s with localized ER/PR-positive, HER2-positive breast cancer and residual disease after neoadjuvant treatment — Ms Leonard (41:29) Case: A woman in her early 70s with metastatic HER2-positive breast cancer — Ms Fulgencio (53:16) Case: A woman in her mid-40s with ER/PR-positive, HER2-positive metastatic breast cancer — Allie Hershey, MSN, RN, ANP-BC, AOCNP (1:02:04) Case: A woman in her mid-60s with ER-positive, HER2-positive metastatic breast cancer and brain metastases — Ms Leonard (1:13:44) Care of Patients with Triple-Negative Breast Cancer (TNBC) (1:18:33) Case: A woman in her early 50s with metastatic BRCA wild-type TNBC, PD-L1-positive — Ms Hershey (1:19:14) NCPD information and select publications
Neste episódio, os especialistas convidados, discutem abordagens que visam melhorar os resultados clínicos no cancro da mama luminal e quais os papéis que os Inibidores das Ciclinas e PIK3CA desempenham em contexto de doença avançada. Dr. Paulo CortesCoordenador do Centro de Oncologia Lusíadas Lisboa e Presidente do Conselho Científico da SPO Drª Joana RibeiroOncologista na Unidade de Mama do Centro Clínico Champalimaud Olho Clínico é um Podcast da MSD de atualização científica, direcionado exclusivamente a Profissionais de Saúde. O conteúdo do mesmo não tem por objetivo induzir qualquer alteração de comportamento na prescrição ou toma de medicamentos. PT-NON-00755 01/2021
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.20.344556v1?rss=1 Authors: Osmak, G., Kiselev, I., Baulina, N., Favorova, O. Abstract: MicroRNAs (miRNAs) are short single-stranded non-coding RNA molecules, which are involved in regulation of main biological processes, such as apoptosis, cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases and data on its function in myocardium are mostly unclear. We identified PIK3CA, RHOA, MAPK3, PAFAH1B1, CTNNB1, MYC, PRKCA, ERBB2, and CDC42 as key genes in the miR-375 regulated network and predicted the possible function of miR-375 in the heart muscle, consisting mainly in the regulation of the Rho-GTPases-dependent signalling pathways. We implemented our algorithm for miRNA function prediction into Python module, which is available at GitHub (https://github.com/GJOsmak/miRNET). Copy rights belong to original authors. Visit the link for more info
Proceedings from the first in a 3-part webinar series. Featuring perspectives from Drs Andrew McKenzie, Bryan P Schneider and Milan Radovich, including the following topics: Part 1: Case Discussions Introduction (00:00) Case: A man in his mid-70s with prostate cancer (AKT1 E17k mutation) — Milan Radovich, PhD and Bryan P Schneider, MD (5:39) Case: A frail woman in her early 80s with endometrial cancer (AKT mutation) — Sulfi Ibrahim, MD (7:45) Case: A man in his late 50s with salivary gland head and neck squamous cell carcinoma (NTRK3-ETV6 fusion) — Andrew McKenzie, PhD (14:53) Case: A man in his early 80s with bladder cancer (tumor mutational burden 67 mut/Mb) — Drs Radovich and Schneider (17:15) Case: A man in his late 60s with muscle-invasive bladder cancer (PIK3CA mutation, RET amplification) — Dr Ibrahim (21:57) Case: A man in his early 60s with cholangiocarcinoma (FGFR2 rearrangement) — Dr McKenzie (25:35) Part 2: FDA-Approved and Guideline-Endorsed Platforms for Genomic Testing Advantages and limitations of available assays (29:33) Part 3: Case Discussions Case: A woman in her mid-60s with glioblastoma (FGFR3-TACC3 fusion) — Drs Radovich and Schneider (39:21) Case: A man in his early 80s with cancer of unknown primary (TMPRSS2-ERG fusion) — Dr Ibrahim (41:43) Case: A woman in her mid-60s with metastatic breast cancer (PIK3CA, ESR1 mutations) — Dr McKenzie (48:03) Case: A woman in her mid-60s with pancreatic cancer (KRAS G12C mutation) — Drs Radovich and Schneider (52:52) Case: A woman in her mid-60s with metastatic adenocarcinoma of the lung (KRAS G12C mutation) — Dr McKenzie (54:45) CME information and select publications
HOPA Now is the official podcast of the Hematology/Oncology/Pharmacy Association, an organization dedicated to supporting pharmacy practitioners and promoting the advancement of Hematology/Oncology/Pharmacy to optimize the care of individuals impacted by cancer. These educational podcasts are part of our BCOP Preparatory and Recertification Course, which is designed to prepare oncology pharmacists preparing to sit for the BCOP Certification Exam, as well as meet the BPS requirement to complete a BCOP Preparatory/Recertification Review Course. In this episode of HOPA Now, Dr. Neelam Patel highlights various drug regimens and recommendations including adjuvant Anti-HER2 therapy, PIK3CA, characteristics of CDK4/6 inhibitors, and considerations for adjuvant chemotherapy. She details the key role that pharmacists can play in helping manage potential toxicities and ends with recommendations on when to stop therapy and how to employ supported care. In this episode you will learn: Breast Cancer Top 10 Clinical Pearls Utilizing adjuvant Anti-HER2 therapy based on residual disease versus no residual disease The relationship between PIK3CA and the place of Alpelisib in therapy Mechanical characteristics of CDK4/6 inhibitors, dosing recommendations, recent changes, and its place in therapy NCCN guidelines for using endocrine therapy versus cytotoxic therapy in metastatic breast cancer Adjuvant chemotherapy for hormone receptor-positive HER2-negative C and findings of the TAILORx study PARP inhibitors used in treating breast cancers and adjuvant Capecitabine Bone modifying therapy and drug dosing recommendations The evaluation of metastatic disease, when to stop therapy, and supported care Mentioned in This Episode: HOPA Quotes: “Ado-trastuzumab emtansine is recommended in the adjuvant setting if patients have residual disease following neoadjuvant HER2 targeted therapy.” — Dr. Neelam Patel “Close monitoring and management is one of the key roles that we can play as pharmacists in helping manage these toxicities.” — Dr. Neelam Patel “If a patient is symptomatic and requires quick disease control, cytotoxic chemotherapy may be recommended.” — Dr. Neelam Patel “In general, chemotherapy is chosen based on patient-specific risk factors.” — Dr. Neelam Patel
Dr. Raja Mudad is a medical oncologist specializing in lung cancer at Florida Precision Oncology. In today's ASCO eLearning Podcast, Dr. Mudad will discuss two patient cases related to the treatment of advanced non-small cell lung cancer harboring an EGFR mutation. While the two cases are similar, the recommended treatments can be different. We hope you enjoy this episode. To hear the latest eLearning Podcast episodes as soon as they are available, please subscribe on Apple Podcasts [https://podcasts.apple.com/us/podcast/asco-elearning-weekly-podcasts/id1375021523] or Google Play [https://play.google.com/music/listen?u=0#/ps/Igjyhvqqrvuc5mjvlljhzkpvgeu]. We truly value your feedback, so please leave a review. To access our entire library of podcasts and other amazing eLearning content, visit elearning.asco.org [https://elearning.asco.org/homepage]. The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello. My name is Raja Mudad. I'm a medical oncologist specializing in lung cancer. I work at Florida Precision Oncology, a practice dedicated to an academic approach in the treatment of cancer. Today, we compare two patient cases that relate to the treatment of advanced stage non-small cell lung cancer harboring an EGFR mutation. These two cases have similarities, yet the recommended treatments may be different. Let us look at the cases. Patient case 1, our first patient case is Roberto. He is a 34-year-old man with stage 4 non-small cell lung cancer harboring an EGFR deletion 19 mutation. The patient, a never smoker, presented with chest pain and was diagnosed with a pulmonary embolus. CT scan of the chest also demonstrated bilateral lung nodules. Biopsy revealed adenocarcinoma. Staging workup revealed multiple small brain metastases. Patient case 2, our second patient case is Heidi. She is a 60-year-old woman with stage four non-small cell lung cancer with an exon 21 mutation in EGFR gene. She presented with a cough. A CT scan of the chest showed a left lung mass. An endobronchial ultrasound guided biopsy revealed no evidence of mediastinal disease. And a biopsy was positive only in the mass showing adenocarcinoma. She was taken to surgery but found to have multiple pericardial nodules. No distant metastases were seen on the PET scan. The two cases are clinically similar. Would any of the differences lead you to select a different treatment for each patient? Let's take a look. The two patients have the exact disease, a similar stage, and mutations in the same EGFR gene. Their initial treatment is the same. The initial treatment in both cases, osimertinib, is considered the standard of care in the United States, with a median progression-free survival of 19 months. Roberto started on treatment with osimertinib, and the follow-up PET scan and brain MRI showed complete resolution of all of the abnormalities. In the second case, surgery was aborted, and the patient started on osimertinib. About 1.5 years after Roberto started on osimertinib, progressive disease developed with a new adrenal mass, a new bone metastasis, and progression in the brain. He received stereotactic radiosurgery to the brain. A repeat biopsy of the adrenal mass revealed the same histology but with a MET amplification detected on next-generation sequencing. About eight months after starting osimertinib, Heidi developed progressive disease, and a repeat biopsy confirmed the same histology and the original EGFR mutation but no additional abnormalities. As you can see, the two cases are similar at presentation. However, upon progression, both cases have peculiarities that make them different. Which differences in the two cases do you think may inform treatment choices? Would the differences lead your choice of treatment in a different direction, or would both patients receive the same treatment? If treatment is different, what is the difference that changes your choice of treatment? The standard of care for non-small cell lung cancer with an EGFR mutation upon progression on first-line tyrosine kinase inhibitor is generally chemotherapy, possibly combined with immunotherapy. In non-small cell lung cancer with an EGFR mutation, there are multiple suggested mechanisms of resistance to osimertinib. These involve new mutations in the EGFR gene, alterations in parallel or downstream oncogenes, such as MET, KRAS, and PIK3CA, or histological transformation to small-cell carcinoma. MET amplification is a very common abnormality seen in those patients. Upon progression, patients have several options, and their treatment should be directed based on the results of the repeat molecular evaluation. That is why it is important to repeat a biopsy on patients with disease progression. Nowadays, liquid biopsy is also helpful in detecting these abnormalities without the need for an actual biopsy. Roberto can benefit from a MET-directed therapy using a tyrosine kinase inhibitor. He did receive stereotactic radiosurgery to the brain due to the presence of mild symptoms. He is clinically doing well, so the need to initiate immediate systemic cytotoxic chemotherapy is not urgent. In this patient, I would offer him an oral MET inhibitor and repeat his imaging in three months. On the other hand, the second patient, Heidi, did not have an actionable mutation upon re-biopsy. The patient is best served by a clinical trial. However, if a trial is not available, or if she is not eligible, then systemic chemotherapy and immunotherapy would be the standard of care. In my practice, and based on the results of the IMpower 150 trial, the use of the combination of carboplatin, paclitaxel, atezolizumab, and bevacizumab is preferred. The subset analysis of the EGFR-positive patients in this trial favored the use of the quadruplet combination. Thank you for listening to this episode of the ASCO eLearning Podcast. For more information on the treatment of non-small cell lung cancer, including additional patient cases and opportunities for self-evaluation, please visit the comprehensive eLearning center at elearning.asco.org. Thank you for listening to this week's episode of the ASCO eLearning weekly podcast. To make this part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.
Oncology Grand Rounds Series: Part 1 — Breast Cancer — Faculty Presentation 2: Case (Ms Marti): A woman in her late 50s with metastatic ER-positive breast cancer and a PIK3CA mutation CME information and select publications
Oncology Grand Rounds Series: Part 1 — Breast Cancer — Faculty Presentation 4: Case (Mr Pizana): A woman in her mid-40s with ER-positive metastatic breast cancer and a PIK3CA mutation CME information and select publications
Proceedings from the first in a series of 11 integrated webinars held in association with the 2020 ONS Annual Congress. Featuring perspectives from Dr Virginia Kaklamani, Ms Marissa Marti, Dr Joyce O’Shaughnessy and Mr Daniel G Pizana. Introduction (00:00) Neoadjuvant therapy for patients with localized HER2-positive breast cancer (2:20) Activity and tolerability of T-DM1 as adjuvant therapy (7:24) Clinical experience with neratinib as postadjuvant therapy for patients with HER2-positive breast cancer (11:00) Results of the KATHERINE study comparing T-DM1 to trastuzumab and the APHINITY trial evaluating pertuzumab, trastuzumab and chemotherapy as adjuvant therapy for HER2-positive early breast cancer (15:48) Benefits and risks with the novel agents trastuzumab deruxtecan and tucatinib for HER2-positive metastatic breast cancer (mBC) (26:13) Role of the immune checkpoint inhibitors atezolizumab and pembrolizumab and the novel antibody-drug conjugate sacituzumab govitecan for triple-negative breast cancer (38:49) Genomic testing for patients with breast cancer; integration of PARP inhibitors into the therapeutic algorithm for patients with mBC and germline BRCA mutations (52:59) Efficacy and tolerability of the CDK4/6 inhibitors palbociclib, abemaciclib and ribociclib for ER-positive, HER2-negative mBC (1:07:56) Activity of alpelisib in patients with ER-positive mBC and PIK3CA mutations; results of the SOLAR-1 trial evaluating alpelisib with fulvestrant (1:16:19) CNE information and select publications
O uso de sequenciamento genômico para identificação de mutações drivers dos tumores mamários bem como o tratamento envolvendo terapia-alvo têm sido cada vez mais frequentes e importantes no controle da doença e melhora na qualidade de vida das pacientes. Estudos importantes envolvendo a análise de biomarcadores dirigidos têm sido realizados, dentre eles o estudo BYLieve, que teve um dos braços apresentados na ASCO 2020. A análise incluiu pacientes com mutação de PIK3CA que haviam progredido ao tratamento padrão de primeira linha com inibidor de aromatase associado a inibidor de CDK4/6 para receberem alpelisibe combinado à fulvestranto. Os resultados corroboram os dados do estudo SOLAR-1, que levaram à aprovação de alpelisibe em 2019 pela ANVISA. Para comentar os resultados deste importante trabalho bem como o método de checagem da mutação PIK3CA disponível atualmente, preparamos este MOC-Dicas, com apresentação do Dr. Antonio C. Buzaid, editor do MOC.
Nesse Podcast discutimos se há atividade de alpelisibe combinado à fulvestranto em pacientes com mutação de PIK3CA que progridem à primeira linha com inibidor de aromatase combinado à inibidor de ciclina 4/6, regime de tratamento gold standard de primeira linha na prática clínica. Confira o episódio, com participação da Dra. Debora Gagliato, oncologista clínica da BP – A Beneficência Portuguesa de São Paulo.
Dr. Becky Nagy, Vice President of Medical Affairs at Guardant Health discusses the phase l/ll study led by Memorial Sloan Kettering Cancer Center and published in "Nature Cancer" that showed Guardant360® liquid biopsy test identifies predictors of response to PIK3CA inhibitors in women with HR+ Metastatic Breast Cancer.
Anna Berghof talks to Matteo Lambertini - Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. The year 2019 has brought relevant new biological and clinical evidence to further improve the care of breast cancer patients. Regarding biological knowledge, in addition to the many important steps forward in enhancing the understanding of several aspects related to tumor biology and treatment resistance, more predictive biomarkers have entered clinical use. In addition to knowing the status of hormone receptors and HER2, other biomarkers should now be tested in different disease subtypes and clinical situations including PD-L1, PIK3CA mutations and germline BRCA mutations. The clinical management of breast cancer patients has also significantly changed. Important evidence has become available to further personalize the choices of the best chemotherapy, endocrine treatment and targeted therapy approaches in both the advanced and early settings. Importantly, for patients with advanced breast cancer including those treated in the first-line setting, overall survival improvements have finally been observed in all disease subtypes thanks to the availability of more effective targeted agents. Many upcoming translational and clinical data are expected in 2020 with a great promise of further changing clinical practice in the breast cancer field. This is the case also for the triple-negative subtype where more effective and targeted treatment options beyond chemotherapy are expected to enter clinical use and improve patients’ outcomes and quality of life. Read the Abstract on the ESMO Open website: https://esmoopen.bmj.com/content/5/3/e000794
A special video supplement to a CME conference held during the 2019 San Antonio Breast Cancer Symposium featuring expert comments on the management of ER-positive breast cancer. Featuring perspectives from Dr Harold J Burstein. Use of genomic classifiers to inform therapeutic decision-making for ER-positive localized breast cancer (00:00) Prognostic and/or predictive utility of the various genomic assays for patients with node-negative and node-positive early breast cancer (03:23) Implications of the TAILORx intermediate-risk cohort results for adjuvant treatment for pre- and postmenopausal patients with localized breast cancer (05:27) Effects of prolonging adjuvant aromatase inhibitor therapy beyond 5 years on recurrence and cause-specific mortality (10:42) NSABP-B-42: Ten-year results of extended adjuvant endocrine therapy with letrozole for postmenopausal women with ER-positive breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) (12:28) Optimizing the use of CDK4/6 inhibitors in the management of ER-positive metastatic breast cancer (mBC); overall survival findings and mechanisms of resistance (14:56) Management of de novo ER-positive, HER2-negative mBC (18:22) Choice of endocrine therapy partner for patients with de novo ER-positive, HER2-negative mBC (21:39) Approach for patients with mBC and disease progression on an AI (24:04) Selection and sequencing of CDK4/6 inhibitors in mBC; comparison of side-effect profiles (26:40) Incidence, identification and prognostic significance of PI3K mutations in patients with ER-positive mBC (31:35) Results of the Phase III SOLAR-1 trial evaluating alpelisib/fulvestrant versus fulvestrant alone for patients with ER-positive, HER2-negative advanced BC with or without a PIK3CA mutation after disease progression on first-line endocrine therapy; FDA approval for breast cancer with a PIK3CA mutation and current clinical role (33:27) Spectrum, frequency and severity of toxicities observed with alpelisib (36:09) Clinical experience with everolimus in mBC; potential for its use after disease progression on a CDK4/6 inhibitor (39:07) Biologic rationale for evaluation of the Bcl-2 inhibitor venetoclax in ER-positive mBC (40:54) Overview of the novel HER2-directed agents trastuzumab deruxtecan and tucatinib for HER2-positive mBC (44:00) Dual targeted approach for patients with ER/PR-positive, HER2-positive mBC (46:40) Investigation of other strategies designed to exploit the PI3K/AKT/mTOR pathway (50:06) Early activity and safety data with the use of CDK4/6 inhibitors as neoadjuvant therapy; ongoing evaluation and potential clinical role (51:08) Perspectives of Dr Burstein and Dr Love on the passing and legacy of the breast cancer revolutionary Dr Bernard Fisher (56:40) Advances in the adjuvant treatment of HER2-positive and triple-negative breast cancer (1:02:24) CME information and select publications
Proceedings from a satellite symposium during the 42nd annual San Antonio Breast Cancer Symposium. Featuring perspectives from Dr Harold J Burstein, Dr Matthew Goetz, Prof Stephen RD Johnston and Dr Joseph A Sparano. Introduction Program Overview: Dr Love (00:00) Use of Genomic Classifiers to Inform Therapeutic Decision-Making for Patients with ER-Positive Localized Breast Cancer (BC) Case (Dr Goetz): A premenopausal woman in her early 40s with a 1.4-cm, ER-positive, HER2-negative, node-negative IDC and a 21-gene Recurrence Score® of 9 (1:14) Case (Prof Johnston): A woman in her late 30s with a 1.8-cm, ER-positive, HER2-negative, node-negative IDC and an intermediate 21-gene Recurrence Score (9:24) Case (Dr Burstein): A woman in her late 50s with a 1.3-cm, ER-positive, HER2-negative IDC and 1 positive sentinel lymph node (11:11) Faculty Presentation: Dr Sparano (13:57) Optimizing the Use of CDK4/6 Inhibitors in the Management of ER-Positive Metastatic BC (mBC) Case (Dr Goetz): A woman in her mid-40s develops liver and bone metastases near the completion of 5 years of letrozole for ER-positive BC (34:52) Faculty Presentation: Dr Goetz (38:28) Case (Dr Sparano): A man in his late 40s presents with de novo ER-positive, HER2-negative mBC to the lung and bones and receives abemaciclib and tamoxifen (51:17) Current and Future Management of ER-Positive mBC After Disease Progression on CDK4/6 Inhibition Case (Dr Sparano): A woman in her early 40s with ER-positive, HER2-negative mBC who has experienced disease progression on multiple lines of endocrine therapy is found to have a PIK3CA mutation (56:48) Case (Dr Goetz): A woman in her mid-40s receives abemaciclib/fulvestrant for ER-positive, HER2-negative mBC but experiences disease progression after 2 years (57:32) Faculty Presentation: Dr Burstein (1:00:03) Novel Applications of CDK4/6 Inhibitors; Ongoing Clinical Trials Faculty Presentation: Prof Johnston (1:16:55) Case (Prof Johnston): A woman in her mid-30s who has experienced disease progression on multiple lines of therapy, including most recently palbociclib/fulvestrant, undergoes multiplex testing, which reveals ESR1 and PIK3CA mutations (1:30:49) CME information and select publications
Genomic Assays in the “Real” Oncology World — Part 2: Genomic Assays in Prostate and Breast Cancer — Featuring a roundtable discussion with Drs Emmanuel S Antonarakis, Johanna Bendell, Ian E Krop and Andrew McKenzie. NGS for Metastatic Prostate Cancer (mPC) and the Potential Clinical Significance of Genomic Alterations Genetic alterations assessed in routine practice, including MSI status, BRCA mutations and AR-V7 variants; role of multiplex testing Presentation (Dr Antonarakis): Biomarker assessment in mPC; detection of DNA damage repair abnormalities and prediction of benefit with PARP and PD-1 inhibitors Landscape of DNA damage repair mutations in newly diagnosed and metastatic prostate cancer Rationale for the use of PARP inhibitors for prostate cancer with BRCA or ATM mutations Genetic testing of primary and metastatic tumors for alterations in the DNA repair and androgen receptor (AR) signaling pathways Clinical significance and genetic detection of AR splice variants Results of the CARD trial: Cabazitaxel versus enzalutamide or abiraterone for patients with mCRPC previously treated with docetaxel who experience rapid disease progression on an AR-targeted agent Efficacy of olaparib for mCRPC Available data with rucaparib, niraparib and talazoparib for mCRPC Role of radium-223 dichloride for patients with mPC; novel combination approaches with radium-223 under investigation Sensitivity of BRCA1, BRCA2 and ATM mutations to PARP inhibitors Activity of PARP inhibitors in patients with breast, ovarian, prostate and pancreatic cancers with BRCA mutations Homologous recombination deficiency and response to PARP inhibitors Case (Dr Antonarakis): A man in his mid-40s with mCRPC and a BRCA2 mutation attains a complete response to olaparib Case (Dr Antonarakis): A man in his mid-60s diagnosed with de novo mPC and MSI-high status, high tumor mutation burden and an MSH2 mutation experiences an excellent response to pembrolizumab after multiple lines of therapy Association of ductal and intraductal prostate cancer with a high prevalence of DNA damage repair gene mutations Predictors of benefit with immune checkpoint inhibitors Multigene Testing and Detection of Genomic Alterations in Metastatic Breast Cancer (mBC) Role of MSI testing and multiplex genomic assays in mBC Assessment of PIK3CA and BRCA mutations and assays for ESR1 Presentation (Dr Krop): Biomarker assessment in mBC — ER-positive and triple-negative disease PTEN loss and implications for therapeutic decision-making for mBC ESR1 mutations and resistance to hormone therapy Efficacy of PARP inhibitors in patients with BRCA mutations HER2 expression in HER2 nonamplified cancers; activity of trastuzumab deruxtecan in HER2-low breast cancer PD-L1 and other biomarkers predictive of benefit from immunotherapy in triple-negative breast cancer (TNBC) Case (Dr Krop): A woman in her late 50s with de novo TNBC receives atezolizumab/nab paclitaxel as first-line therapy Case (Dr Krop): A woman in her early 60s with ER-positive, HER2-negative mBC and a germline BRCA2 mutation whose disease progresses through multiple therapies attains a partial response to olaparib The Sarah Cannon Experience with Molecular Tumor Boards The use of molecular tumor boards to review molecular profiling data and facilitate therapeutic decision-making CME information and select publications
Oncotarget interviews Dr. Beatrice Aramini from the University of Modena and Reggio Emilia in Modena Italy about their Featured Cover Paper for Volume 11 Issue 5 titled "Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study" PRESS RELEASE: The cover for issue 5 of Oncotarget features Figure 2, "Survival curves in the KRAS, EGFR, and niche mutations cohorts," by Aramini, et al. Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET. The multivariable analysis showed that: Niche mutations had higher mortality than EGFR mutations KRAS mutations had higher mortality than EGFR mutations, and Niche mutations presented similar mortality to KRAS mutations. Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations. Dr. Beatrice Aramini from the Division of Thoracic Surgery in Department of Medical and Surgical Sciences at the University of Modena and Reggio Emilia in Modena Italy said in their Oncotarget Research Paper, "In the last century, carcinoma of the lung has progressed from an uncommon and obscure disease to the most common cancer in the world, and the most common cause of death from cancer." In addition to these somatic mutations, which are the most frequent, other mutations in several genes have been discovered, including BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations. Moreover, the prevalence of the RET mutation in adenocarcinoma was estimated to be 1.7%, and the prevalence of DDR2 mutation in lung cancer was 2.2%. With regard to treatment, discoveries of gene mutations have allowed the development of targeted therapies, which are considered more effective for survival than chemotherapy in patients with advanced mutated disease. Considering the potential aggressiveness of niche mutations in this context, the technological advances of next-generation sequencing, which is currently used in clinical practice, represents a precise approach to identifying a large panel of mutations in oncologic patients. The Armini Research Team concluded, "The correct selection of mutations will be helpful in terms of the greater efficacy of treatment in association with better prognosis and a higher quality of life for oncologic patients." Full text - https://doi.org/10.18632/oncotarget.27472 Correspondence to - Beatrice Aramini,beatrice.aramini@unimore.it Keywords - somatic mutations, non-small cell lung cancer (NSCLC), lung cancer treatment, overall survival, target therapy Sign up for free Altmetric alerts about this article About Oncotarget Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with: YouTube - http://bit.ly/OncotargetYoutube SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
PRESS RELEASE: Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study The cover for issue 5 of Oncotarget features Figure 2, "Survival curves in the KRAS, EGFR, and niche mutations cohorts," by Aramini, et al. Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET. The multivariable analysis showed that: Niche mutations had higher mortality than EGFR mutations KRAS mutations had higher mortality than EGFR mutations, and Niche mutations presented similar mortality to KRAS mutations. Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations. Dr. Beatrice Aramini from the Division of Thoracic Surgery in Department of Medical and Surgical Sciences at the University of Modena and Reggio Emilia in Modena Italy said in their Oncotarget Research Paper, "In the last century, carcinoma of the lung has progressed from an uncommon and obscure disease to the most common cancer in the world, and the most common cause of death from cancer." In addition to these somatic mutations, which are the most frequent, other mutations in several genes have been discovered, including BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations. Moreover, the prevalence of the RET mutation in adenocarcinoma was estimated to be 1.7%, and the prevalence of DDR2 mutation in lung cancer was 2.2%. With regard to treatment, discoveries of gene mutations have allowed the development of targeted therapies, which are considered more effective for survival than chemotherapy in patients with advanced mutated disease. Considering the potential aggressiveness of niche mutations in this context, the technological advances of next-generation sequencing, which is currently used in clinical practice, represents a precise approach to identifying a large panel of mutations in oncologic patients. The Armini Research Team concluded, "The correct selection of mutations will be helpful in terms of the greater efficacy of treatment in association with better prognosis and a higher quality of life for oncologic patients." Full text - https://doi.org/10.18632/oncotarget.27472 Correspondence to - Beatrice Aramini,beatrice.aramini@unimore.it Keywords - somatic mutations, non-small cell lung cancer (NSCLC), lung cancer treatment, overall survival, target therapy Sign up for free Altmetric alerts about this article About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with: YouTube - http://bit.ly/OncotargetYoutube SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Lauren Davis, and joining me today is Dr. Megan Cruz, a medical oncologist at the Cleveland Clinic who treats patients with breast cancer. ASCO Daily News: Today we're talking about a new therapeutic option for patients with metastatic breast cancer who carry the PIC3CA mutation. Dr. Cruz, welcome to the podcast. Dr. Megan Cruz: Good morning. Thank you for having me. ASCO Daily News: We're glad you're here. ASCO Daily News: So the PIK3CA is a commonly mutated gene in HR positive and HER2 negative advanced breast cancer. What kind of tests are used to detect this mutation? Dr. Megan Cruz: Yes, so that's correct. The PI3 kinase mutation is found in about 40% of hormone receptor positive HER2 negative advanced breast cancer cases. And this mutation can actually be detected by a variety of tests, many of which are convenient for our patients. Dr. Megan Cruz: Most commonly, we use tissue-based testing. And that can be samples of tissue that have been archived from either a patient's initial breast cancer diagnosis or a newer biopsy from a metastatic site. If neither of those places can be accessed or that tissue sample is no longer available, patients can have testing run on a blood-based sample. And this is often very helpful for patients who potentially have bone-only metastatic disease. ASCO Daily News: Are new agents are available to treat this form of cancer? Dr. Megan Cruz: Yes. So earlier this year, we had FDA approval of a new medication called alpelisib, which is used in combination with endocrine-based therapy in the form of fulvestrant in order to treat patients with the PI3 kinase mutated breast cancer. ASCO Daily News: And how effective is this treatment in terms of survival or overall survival? Dr. Megan Cruz: So this treatment was studied in the SOLAR-1 trial. And in that trial, it was found that there was a progression-free survival advantage for patients who received the combination of alpelisib and fulvestrant compared to placebo and fulvestrant. And that difference at 20 months was approximately from 11 months with alpelisib and fulvestrant from 5.7 months for the placebo fulvestrant combination. ASCO Daily News: And what do clinicians need to know about side effects? Dr. Megan Cruz: So there are some unique side effects with this medication, alpelisib, that clinicians will need to pay attention to. The most common ones are hypoglycemia and rash, which are generally pretty easily managed, but we have to be aware of them. Dr. Megan Cruz: When starting a patient on this medication, they need to have fasting blood sugar testing as well as hemoglobin A1C testing done prior to starting as a baseline. And then shortly after initiation of the medication, we recheck these labs to make sure that they're staying stable. Dr. Megan Cruz: If the blood sugar is rising, it's recommended to do more frequent monitoring and consideration of starting a medication like metformin to help control the blood sugars. In terms of the rash, that can actually be dealt with in a preventative way, where patients can be started on prophylactic antihistamine medications along with the start of alpelisib. And then if the rash does happen once they're on the medication, we often use either topical steroids or oral steroids to help control it. Dr. Megan Cruz: The last toxicity that I think that the clinicians should be aware of his diarrhea, which is one that we're more familiar with managing from other chemotherapies and targeted agents. So typically, use of our common anti-diarrheal medications will help to control that. ASCO Daily News: What do you think's on the horizon for metastatic breast cancer treatment? Dr. Megan Cruz: I think that we will continue to see medications like this that are targeted for specific mutations that we find in a patient's breast cancer. And then along with that, I think we'll be combining these targeted medications potentially with immunotherapy moving forward. I think those are the new horizons for metastatic breast cancer treatment. ASCO Daily News: Again, today my guest has been Dr. Megan Cruz. It's been a pleasure speaking with you. Thank you for being on our podcast. Dr. Megan Cruz: Absolutely. Thanks for having me. ASCO Daily News: And to our listeners, thank you for tuning into the ASCO Daily News Podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Breast Cancer Update, Issue 3, 2019 — Part 1: Our interview with Dr Goetz highlights the following topics as well as cases from his practice: Case: A woman in her mid-30s with de novo ER-positive, HER2-negative metastatic breast cancer (mBC) achieves a complete clinical response to palbociclib, letrozole and ovarian suppression (00:00) Importance of providing support to patients and their families coping with a diagnosis of mBC (01:15) Therapeutic options for patients with de novo ER-positive, HER2-negative mBC (03:45) Activity and tolerability of gonadotropin-releasing hormone agonists (05:35) Selection of patients for treatment with CDK4/6 inhibitors in combination with endocrine therapy (09:07) Mechanism of action of CDK4/6 inhibitors (12:13) Role of everolimus and alpelisib in the management of ER-positive mBC (14:30) Implications of ESR1 mutations for the management of ER-positive mBC; use of selective estrogen receptor degraders (SERDs) (16:15) Activity of the selective estrogen receptor modulators endoxifen and lasofoxifene for mBC with ESR1 mutation (19:48) Tolerability profiles of the CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib; dose reduction to mitigate side effects (21:21) CNS penetration of abemaciclib; management of abemaciclib-associated diarrhea (25:26) Effects of site and extent of metastases on outcomes with CDK4/6 inhibitors (27:02) Efficacy of CDK4/6 inhibitors in combination with endocrine therapy for ER-positive mBC (29:29) Survival outcomes with CDK4/6 inhibitors and endocrine therapy for ER-positive mBC (31:28) Response to palbociclib and endocrine therapy in patients with ER-positive mBC (34:17) Selection of therapy for patients with locally advanced ER-positive, HER2-negative breast cancer (36:41) Therapeutic approach for patients who experience disease progression on a CDK4/6 inhibitor (39:33) Activity of alpelisib for ER-positive advanced breast cancer with a PIK3CA mutation (47:02) Side-effect profile of alpelisib (49:41) Case: A woman in her late 60s with high-grade, ER-positive, HER2-negative breast cancer and a 21-gene assay Recurrence Score (RS) of 52 receives adjuvant chemotherapy (52:54) Role of bone-modifying agents for patients with ER-positive breast cancer and bone metastases (58:04) Ongoing investigations of CDK4/6 inhibitors in the adjuvant setting (59:40) Effects of CDK4/6 inhibitors on immunity; potential for combination with immune checkpoint inhibitors (1:01:14) TAILORx trial: Adjuvant chemotherapy guided by a 21-gene expression assay for women with ER-positive, HER2-negative, node-negative breast cancer (1:06:19) Impact of clinical risk on prognosis and prediction of chemotherapy benefit by age and RS in the TAILORx study for patients with early breast cancer (1:07:46) Perspective on the use of gene expression assays to determine risk of recurrence and guide adjuvant decision-making (1:14:30) Cancer cell dormancy and risk of late recurrence (1:16:47) CME information and select publications
Breast Cancer Update, Issue 3, 2019 — Part 2: Our interview with Dr Kaklamani highlights the following topics as well as cases from her practice: Efficacy and safety of the novel SERD elacestrant for ER-positive breast cancer; Phase III EMERALD trial evaluating elacestrant versus endocrine therapy (00:00) Incidence of ESR1 mutations; activity of elacestrant after disease progression on fulvestrant and a CDK4/6 inhibitor (02:14) Results from the Phase II ANETT trial of the mTORC1/2 inhibitor TAK-228 with tamoxifen as neoadjuvant therapy for ER-positive breast cancer (03:53) Novel approaches under investigation in the neoadjuvant setting (07:20) Perspective on the use of neoadjuvant therapy to optimize surgical outcomes for patients with ER-positive, HER2-negative breast cancer (09:43) Activity of CDK4/6 inhibitors for locally advanced ER-positive breast cancer (11:30) Case: A woman in her late 60s with ER-positive, HER2-negative breast cancer and 1 of 3 positive axillary lymph nodes receives a 21-gene assay RS of 18 (13:49) Role of the 21-gene expression assay in predicting chemotherapy benefit for patients with ER-positive breast cancer (15:56) Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer (19:11) Case: A premenopausal woman in her late 40s with ER-positive, HER2-negative, node-negative breast cancer receives a RS of 19 (23:19) Clinical implications of the TAILORx trial comparing chemoendocrine therapy to endocrine therapy for patients with ER-positive, node-negative breast cancer and an intermediate RS (25:00) Tailoring adjuvant endocrine therapy for premenopausal women with ER-positive breast cancer (27:54) Benefit of endocrine therapy with or without chemotherapy for patients with ER-positive breast cancer and an intermediate RS; consideration of clinical and genomic risk in assessing the likelihood of disease recurrence (30:54) Case: A woman in her early 40s with ER-positive, HER2-negative breast cancer and metastases in the liver and bones attains a partial response to ribociclib in combination with endocrine therapy (35:24) Benefit with CDK4/6 inhibitors versus chemotherapy for ER-positive breast cancer with visceral metastases (37:57) Efficacy of ribociclib in premenopausal women; QT prolongation associated with ribociclib/tamoxifen (40:54) Comparison of the efficacy and toxicity profiles of abemaciclib, palbociclib and ribociclib for women with ER-positive mBC (42:24) Activity of CDK4/6 inhibitors as monotherapy; CNS penetration of CDK4/6 inhibitors (45:47) Monitoring and management of side effects associated with CDK4/6 inhibitors (48:07) Case: A woman in her mid-50s initially diagnosed with Stage II ER-positive breast cancer develops metastatic disease to the bone 8 years later and receives palbociclib and anastrozole (50:54) Perspective on the use of multiplex genomic assays to guide treatment decision-making for patients with ER-positive mBC (53:35) Results of the Phase III SOLAR-1 trial evaluating alpelisib for patients with ER-positive advanced breast cancer (55:54) Tolerability of alpelisib for patients with ER-positive breast cancer (57:54) Sequencing everolimus and alpelisib after disease progression on a CDK4/6 inhibitor (1:00:06) Case: A postmenopausal woman in her mid-30s with ER-positive mBC and BRCA2 and PIK3CA mutations receives talazoparib in the third-line setting (1:01:46) Choice of PARP inhibitor for patients with advanced breast cancer and BRCA mutations (1:04:58) Response and side-effect profiles of alpelisib (1:06:10) Selection and sequencing of therapy for patients with mBC and germline BRCA mutations (1:07:00) CME information and select publications
RADIO AND SATELLITE INTERVIEW OPPORTUNITY THURSDAY, JUNE 27th, 2019, 7:30-NOON ET FDA APPROVES FIRST-OF-ITS-KIND TREATMENT FOR METASTATIC BREAST CANCER PATIENTS WITH A SPECIFIC MUTATION Breast Cancer Expert and Patient Advocate Discuss Why Mutations Matter for Postmenopausal Women, and Men, Living with Metastatic Breast Cancer AVAILABLE FOR INTERVIEW Dr. Virginia Kaklamani, Professor of Hematology/Oncology at UT Health San Antonio Shirley Mertz, President of the Metastatic Breast Cancer Network (MBCN) Americans are more aware than ever about genetic testing and mutations in metastatic breast cancer, such as the increased risks associated with the BRCA1/2 gene. What they may not know is that tumors can develop mutations that impact how the breast cancer responds to treatment. Following a recent FDA approval of a new medicine, postmenopausal women and men living with HR+/HER2- metastatic breast cancer who have progressed on or after an endocrine-based regimen may be eligible for treatment if a PIK3CA mutation is detected. The FDA recently approved a new medication to treat women who have gone through menopause and men who haveHR+/HER2- advanced breast cancer or breast cancer that has spread to other parts of the body (metastatic). Thisimportant milestone marks the first time physicians are able to test advanced or metastatic breast cancer patients for aspecific mutation and develop a personalized treatment plan. Mutations of this kind occur in approximately 40% of HR+/HER2- breast cancers, the most common type of breast cancer. The mutations may lead to tumor growth, cause resistance to endocrine therapies and result in a poor overall prognosis. Dr. Virginia Kaklamani, Professor of Hematology/Oncology at UT Health San Antonio , is available to discuss this newtreatment option for patients. Shirley Mertz, President of the Metastatic Breast Cancer Network (MBCN), is also available to share her perspective on the importance for patients of knowing their breast cancer type. SUGGESTED INTERVIEW QUESTIONS Shirley and Dr. Kaklamani, why is this FDA approval significant? Shirley, in your experience as an advocate, how does HR+/HER2- metastatic breast cancer impact the lives of men and postmenopausal women? Shirley, what does it mean to have a new treatment option available for patients living with HR+/HER2- metastatic breast cancer with a PIK3CA mutation? Dr. Kaklamani, how do PIK3CA mutations affect prognosis and progression in HR+/H
Breast Cancer Update, Issue 2, 2019 — Part 1: Our interview with Dr Hurvitz highlights the following topics as well as cases from her practice: Optimal duration of adjuvant trastuzumab; analysis of the results from the Phase III PERSEPHONE and PHARE studies (00:00) Perspective on the role of trastuzumab biosimilar agents in the management of HER2-positive breast cancer (04:43) Benefits and risks of anthracycline-containing and anthracycline-free neoadjuvant regimens for patients with HER2-positive disease (08:03) Comparison of paclitaxel/trastuzumab/pertuzumab to TCHP in the neoadjuvant setting (11:17) Activity of pertuzumab in combination with T-DM1 in the (neo)adjuvant and metastatic settings (13:21) Case: A woman in her mid-40s with ER-positive, HER2-positive breast cancer attains a good response to neoadjuvant T-DM1/pertuzumab on the KRISTINE study (16:15) KRISTINE: A Phase III study of neoadjuvant TCHP versus T-DM1/pertuzumab for HER2-positive breast cancer (19:05) Primary analysis of SOPHIA: A Phase III study of the novel anti-HER2 antibody margetuximab and chemotherapy versus trastuzumab and chemotherapy for pretreated HER2-positive mBC (22:58) Case: A woman in her late 40s with HER2-positive mBC receives trastuzumab deruxtecan on a clinical trial after experiencing disease progression on tucatinib (27:17) Ongoing Phase II HER2CLIMB study investigating tucatinib with capecitabine and trastuzumab for advanced HER2-positive breast cancer (31:06) Emerging data with trastuzumab deruxtecan for patients with advanced HER2-positive breast cancer who received prior treatment with T-DM1 (33:32) Potential clinical role of trastuzumab deruxtecan (37:10) Preemptive measures to mitigate nausea and the risk of pneumonitis associated with trastuzumab deruxtecan (38:45) Case: A woman in her early 40s with HER2-positive mBC experiences a prolonged remission with trastuzumab and lapatinib in combination with chemotherapy (41:22) Predictors of benefit with HER2-targeted therapy; risk of recurrence for patients with HER2-positive breast cancer (47:05) Role of CDK4/6 inhibitors for patients with ER-positive, HER2-positive mBC; activity of PI3K inhibitors in patients with PIK3CA mutations (50:30) Neratinib and capecitabine versus lapatinib and capecitabine for HER2-positive mBC previously treated with HER2-directed therapy: Findings from the Phase III NALA trial (52:40) CME information and select publications
CME credits: 0.50 Valid until: 06-08-2020 Claim your CME credit at https://reachmd.com/programs/cme/hrher2-negative-breast-cancer-revolutions-precision-medicine-pi3k-inhibitors/10857/ Approximately 40% of patients with HR+ breast cancer harbor PIK3CA mutations, which are associated with a poor prognosis. The phosphoinositide 3-kinase (PI3K) pathway is the most frequently altered pathway in breast cancer and has been associated with resistance to endocrine therapy and disease progression. PI3K inhibitor combination therapy has shown activity in patients with PIK3CA mutation–positive HR+/HER2− breast cancer after showing moderate efficacy and limited tolerability in clinical trials as monotherapy. This activity will review the most recent clinical data and evidence-based updates and provide expert insights on PI3K inhibitors for HR+/HER2− advanced or metastatic breast cancer.
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Dr O'Regan speaks with ecancertv at SABCS 2016 about the outcomes of the phase III BELLE-3 trial, in which post-menopausal women with advanced or metastatic HR positive breast cancer who had disease progression during or after mTOR inhibitor therapy were treated with buparlisib and fulvestrant. While the combination improved progression free survival at 6 months, as gauged by PIK3CA status, she notes the dose reductions and adverse events among a small number of patients in the trial, including incidences of depression and suicidal ideation.
Dr O'Regan presents data at the 2016 San Antonio Breast Cancer Symposium from the BELLE-3 trial of buparlisib and fulvestrant for post-menopausal women with locally advanced or metastatic breast cancer who have progressed after mTOR inhibitory therapy. With a primary endpoint of improved progression-free survival, and secondary endpoints of assessing risk through PIK3CA expression, she describes this trial as a success, but notes a slight incidence of psychological effects on a minority of patients, which may be due to the small size of buparlisib permitting it to cross the blood brain barrier.
Dr Campone talks to ecancertv at SABCS 2015 about the first results from the randomised, phase III BELLE-2 trial that assessed the the efficacy and safety of combining the PI3K inhibitor buparlisib with the endocrine therapy fulvestrant in postmenopausal women with endocrine resistant, hormone receptor (HR)-positive, HER2-negative metastatic breast cancer. Activation of the PI3K pathway is a hallmark of resistance to endocrine therapy, Dr Campone explains. Early data suggest that using a PI3K inhibitor may be able to help reverse endocrine resistance and so the BELLE-2 trial was designed to look at this question further. More than 1,140 women who were refractory to aromatase inhibitor therapy were enrolled into the study and stratified based on their PI3K pathway status measured in archival tumor tissue. A 22% reduction in PFS was seen comparing buparlisib plus fulvestrant versus fulvestrant plus placebo in the full population, with respective median PFS of 6.9 and 5 months (p < .001). Pre-specified analyses showed that characterizing PIK3CA mutation in circulating tumour DNA at trial entry could identify patients that may benefit from the buparlisib/fulvestrant combination.
Dr Ring talks to ecancertv at SABCS 2013 about the 'Add-aspirin trial'. This is a phase III double-blind placebo-controlled randomized trial assessing the addition of aspirin after standard primary therapy in breast cancer and other early stage common solid tumours. The primary outcome will be disease-free survival. Secondary endpoints include overall survival, toxicity, cardiac morbidity and assessment of overall healthcare benefits. Translational work will investigate mechanisms of action and biomarkers for toxicity and treatment efficacy (including PIK3CA mutation status and COX-2 expression). Approximately 3100 patients will be needed to test for a 4% improvement in disease free survival associated with aspirin use.
Dr Loibl talks to ecancertv at SABCS 2013 about her study "PIK3CA mutation predicts resistance to anti-HER2/chemotherapy in primary HER2-positive/hormone-receptor-positive breast cancer". Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer, PIK3CA mutations being the most common. Mutations are frequently found in hot-spots located in the helical and kinase domains (exons 9 and 20). Reported data is discrepant with regard to prognostic or predictive value of PIK3CA mutations especially in HER2 positive breast cancer. The team investigated the frequency and prognostic associations of PIK3CA mutations in HER2 positive and triple negative primary breast cancer treated with neoadjuvant therapy. Patients with PIK3CA mutant HER2 positive / HR negative breast cancer are resistant to chemotherapy and dual anti-HER2 treatment. Other treatment options are needed to be tested in this group.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 15/19
Thu, 18 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15644/ https://edoc.ub.uni-muenchen.de/15644/1/Blankenstein_Thomas.pdf Blankenstein, Thomas