Podcasts about Trastuzumab

In this episode, listen to Stephanie L. Graff, MD, FACP, FASCO; and Laura M. Spring, MD, share their clinical insights and takeaways regarding the current treatment landscape for first-line treatment of patients with HER2-positive metastatic breast cancer including:Data from multicenter, single-arm, phase IIIb/IV DESTINY-Breast12 evaluating trastuzumab deruxtecan (T-DXd) in patients with advanced HER2-positive metastatic breast cancer and 2 or fewer previous therapiesTreatment sequencing and preferred treatment options in patients with brain metastasesResults from phase III PATINA trial of trastuzumab, pertuzumab, plus endocrine therapy with or without palbociclib in hormone-receptor positive/HER2-positive metastatic breast cancerThoughts on the use of T-DXd earlier in the treatment paradigm in light of recent results from the PATINA trial and highly anticipated results from the DESTINY-Breast09 trialProgram faculty:Stephanie L. Graff, MD, FACP, FASCODirector of Breast Oncology, Brown University HealthCo-Lead, Breast Cancer Translational Disease Research GroupLegorreta Cancer Center at Brown UniversityAssociate Professor of MedicineWarren Alpert Medical School of Brown UniversityProvidence, Rhode IslandLaura M. Spring, MDBreast Medical OncologistMass General Hospital Cancer CenterHarvard Medical SchoolBoston, Massachusetts Resources:To access the patient cases associated with this podcast discussion, please visit the program page and register for an upcoming webinar on this topic.

It's Thursday, March 6th, 2025. This is Nelson John, let's get started.  ITC Hotels' Rough Debut January 29 was supposed to be a landmark day for ITC Hotels as it began trading independently. However, shares debuted nearly 30% below the implied price, dampening initial enthusiasm. Despite this, analysts remain bullish, valuing the company between ₹42,500-₹62,000 crore. ITC Hotels aims to expand to 200 hotels with 18,000 rooms in five years, relying on managed properties. However, investors worry about its limited owned-hotel pipeline. As competitors like IHCL and Marriott ramp up expansion, ITC Hotels must carve out its niche in a booming industry. Coforge's Record-Breaking Deal Coforge Ltd soared 8% after securing a record 13-year, $1.56 billion deal with US travel tech giant Sabre Corp. This long-term contract ensures strong revenue visibility for FY26, even as tech budgets shrink. Coforge also acquired Rythmos Inc. for $48.7 million and TMLabs for $12.5 million, further expanding its portfolio. A 1:5 stock split was announced to boost liquidity. However, Sabre's $5.1 billion debt raises cash collection concerns. Despite this, Coforge has outperformed peers, with its December order book reaching $1.4 billion—up 40% YoY. Tesla, Tariffs & Trump India's sky-high auto tariffs—up to 110%—have kept foreign automakers like Tesla out, despite Elon Musk's repeated attempts to enter the market. Now, US President Donald Trump has joined the fight, slamming India's “unfair” tariffs and threatening retaliatory action. As trade negotiations intensify, India has begun cutting duties on luxury vehicles—a possible opening for Tesla. With Trade Minister Piyush Goyal in the US for talks, the world watches to see if India will open its doors to global carmakers or protect its domestic industry. Cancer Drug Prices Set to Fall Cancer treatment in India is notoriously expensive, with some drugs costing up to ₹2 lakh per month. That's changing, thanks to domestic production under the government's PLI scheme. Leading pharma firms like Sun Pharma, Cipla, and Biocon are now manufacturing key cancer drugs, significantly cutting prices. For example, Trastuzumab, once ₹70,000 per month, now costs ₹12,000. More price reductions are expected as local production scales up. The initiative not only benefits Indian patients but also strengthens India's role as the “pharmacy of the world,” with exports to South America and Africa. Rupee Rises Amid Market Rally The rupee strengthened by 19 paise to close at 87.00 against the US dollar, supported by a rally in domestic equities, a weaker dollar, and falling crude oil prices. Volatility remained high, with the currency fluctuating between 86.93 and 87.20. Meanwhile, the dollar index slipped 0.79% amid Trump's escalating tariff moves. Brent crude also declined 0.75% to $70.51 per barrel. Markets responded positively, with the Sensex surging 740 points to 73,730 and the Nifty rising 255 points to 22,337. However, FII outflows and ongoing trade uncertainties could limit further rupee gains.

Host: Jacob Sands, MD Guest: Julia Rotow, MD In non-squamous non-small cell lung cancer (NSCLC), a small percentage of patients will have activating HER2 mutations. For these patients, the standard second-line therapy is docetaxel, but this can have poor response rates. That's why the DESTINY-Lung03 trial examined the safety and efficacy of trastuzumab deruxtecan in patients with pretreated HER2-overexpressing non-squamous NSCLC. Here with Dr. Jacob Sands to share the findings from part 1 of this trial is thoracic medical oncologist Dr. Julia Rotow.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in multiple cancers, including breast, gastric, colorectal, and epithelial ovarian cancers. However, this receptor's complexity doesn't stop there. It has multiple subdomains and various responses to drugs, and the complete picture is yet to be understood.This week, we explore the original wonder drug (Trastuzumab) in the early breast cancer space and its compatriot, Pertuzumab. Josh highlights the association between pathological complete responses and event-free survival/overall survival, while Michael looks at Neosphere and picks apart the data to help understand where this drug is most beneficial.Studies discussed in the episode:NEOSPHEREGEPARQUINTONOAH TRIALFor 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 AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have no editorial rights or early previews, and they have access to the episode at the same time you do. Hosted on Acast. See acast.com/privacy for more information.

Welcome to another episode of the Oncology Brothers! In this episode, hosts Drs. Rahul and Rohit Gosain dive into the complexities of managing side effects associated with antibody drug conjugates (ADCs). Joined by expert guests Dr. Tian Zhang, a GU medical oncologist from UT Southwestern, and Dr. Erika Hamilton from Sarah Cannon Research Institute, the discussion focuses on three key ADCs: Enfortumab vedotin, Sacituzumab govitecan, and Trastuzumab deruxtecan (TDXD). Episode Highlights: •⁠  ⁠Enfortumab vedotin: Learn about the common side effects such as skin toxicities, hyperglycemia, and neuropathy, and how to manage them effectively in clinical practice. •⁠  ⁠Sacituzumab govitecan: Explore the challenges of neutropenia, diarrhea, and fatigue, and the importance of individualized patient care. •⁠  ⁠Trastuzumab deruxtecan (TDXD): Understand the critical side effects including nausea, fatigue, and interstitial lung disease (ILD), and the strategies for prevention and management. This episode emphasizes the importance of recognizing and acting on side effects that can significantly impact patient outcomes. Whether you're a healthcare professional or someone interested in oncology, this discussion will provide valuable insights into toxicity management for ADCs. Don't forget to like, subscribe, and check out more episodes for in-depth discussions on oncology topics! Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

In this episode of the Top 200 Drugs Podcast, we cover medications 126-130. Trastuzumab is a monoclonal antibody that can be used for breast cancer that expresses the HER2 protein. Atripla is an HIV medication that contains three separate medications that are beneficial in reducing viral load. Rivaroxaban is an anticoagulant that may be commonly used in the management of stroke and deep vein thrombosis. Fioricet is a combination of three medications. Butalbital, acetaminophen, and caffeine are the three ingredients in this medication. Insulin detemir is a long-acting insulin analog that lowers blood sugar. This medication is used to target fasting blood sugars.

“Although the patient is spending a little less time in the clinic, the administration actually requires the nurse to be at the chairside the entire time. This has allowed nurses to spend potentially uninterrupted time to sit and converse with the patients that they may not have had with an IV infusion. It's been a wonderful unintentional outcome from the development of the large-volume subcutaneous injections,” Crystal Derosier, MSN, RN, OCN®, clinical specialist at Dana-Farber Cancer Institute, in Boston, MA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about administering high-volume subcutaneous injections in cancer care. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by November 22, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: The learner will report an increase in knowledge related to the administration of high-volume subcutaneous injections. Episode Notes  Complete this evaluation for free NCPD.  Oncology Nursing Podcast™ episodes: Episode 326: Intramuscular Injections: The Oncology Nurse's Role Episode 285: Transarterial Chemoembolization: The Oncology Nurse's Role Episode 271: Intraventricular and Intrathecal Administration: The Oncology Nurse's Role Episode 265: Intravesical Administration: The Oncology Nurse's Role Episode 252: Intraperitoneal Administration: The Oncology Nurse's Role ONS Voice articles: Administration Considerations Amid the Large-Volume Subcutaneous Injection Revolution FDA Approves Atezolizumab and Hyaluronidase-Tqjs for Subcutaneous Injection Make Subcutaneous Administration More Comfortable for Your Patients Oncology Drug Reference Sheet: Pertuzumab, Trastuzumab, and Hyaluronidase-Zzxf Subcutaneous Injection ONS Voice Oncology Drug Reference Sheets ONS book: Access Device Guidelines: Recommendations for Nursing Practice and Education (Fourth Edition) ONS course: ONS/ONCC Chemotherapy Immunotherapy Certificate™ Clinical Journal of Oncology Nursing article: Subcutaneous Administration: Evolution, Challenges, and the Role of Hyaluronidase Oncology Nursing Forum article: Administration of Subcutaneous Monoclonal Antibodies in Patients With Cancer To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an Oncology Nursing Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “Some challenges with subcutaneous injections are with the administration, especially when we're thinking about large-volume drugs. … Some of these patients who have been through multiple therapies, they've been on a long journey, or just in general they may have small amounts of subcutaneous injection areas and tissues, so that could be problematic. … Also, some patients may want to go back to receiving IV medications if they experience severe pain at an injection site during administration, or maybe they had a site-related reaction. This is where the nurses play a huge, crucial role in the administration of these subcutaneous drugs.” TS 5:17 “When administering large-volume subcutaneous injections, good ergonomics is very important during the administration because this can help reduce the fatigue and discomfort not only for [nurses] but for the patients as well. If you're trying to hold the needle in place for 5–10 minutes, it's a lot of work. Your arms can start to shake, and that shaking can cause discomfort for the patient as well. The utilization of a winged infusion set for these large volumes allows more space between the patient and the nurse, which supports better ergonomics.” TS 11:20 “When they came to the market, there was an unfounded concern from patients and practitioners that these injections would not be as effective as their IV counterparts. This is totally incorrect. We know that these options have the same efficacy and may actually also help to reduce the incidence of any infusion-related reactions, as well as lower side-effect impacts on patients, so overall, a lot of improvement with these high-volume subcutaneous injections for the patient experience.” TS 21:37 “I'm just really looking forward to the future landscape of oncology practice and drug approvals and drug administration. It's so important that subcutaneous injections have really made a name for themselves in nursing practice today. We continue to see more subcutaneous formulations on the market that are available for patients, allowing them less time in infusion chairs and more flexibility and freedom outside of the healthcare setting.” TS 24:39

OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions. In today's episode, we had the pleasure of speaking with Susana M. Campos, MD, MPH, about the role of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in patients with HER2-positive gynecologic cancers. Dr Campos is the clinical director and the director of Educational Initiatives in the Division of Gynecologic Oncology at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts. In our exclusive interview, Dr Campos discussed the clinical implications of findings from the gynecologic cancer cohorts of the phase 2 DESTINY-PanTumor02 trial (NCT04482309).

Join us in this exciting episode of the Oncology Brothers podcast as we dive into the highlights from ESMO 2024, focusing on gastrointestinal malignancies. Hosts Drs. Rohit and Rahul Gosain are joined by Dr. Kristen Ciombor, a GI medical oncologist from Vanderbilt University, to discuss four key studies that have significant implications for clinical practice. In this episode, we covered: •⁠ ⁠LEAP-012 Study: An update on HCC treatment with Lenvatinib and Pembrolizumab combined with TACE, exploring the promising progression-free survival (PFS) data and the need for mature overall survival (OS) results. •⁠ ⁠Keynote-811: The current standard of care for HER2-positive gastroesophageal junction and gastric adenocarcinoma, highlighting improved OS with Pembrolizumab, chemotherapy, and Trastuzumab. •⁠ ⁠POD1UM-303 Trial: A groundbreaking study in metastatic anal cancer that shows significant OS improvement with the addition of the PD-1 inhibitor Retifanlimab to chemotherapy. •⁠ ⁠NICHE-2 Study: A remarkable update on MSI-high patients, showcasing a 100% three-year disease-free survival rate with neoadjuvant immunotherapy. Tune in for an insightful discussion that will keep you updated on the latest advancements in GI oncology! Don't forget to like, subscribe, and hit the notification bell for more conference highlights and oncology discussions. #OncologyBrothers #ESMO24 #GIMalignancies #CancerResearch #Podcast Subscribe for more updates and insights from the Oncology Brothers! Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com  

Elizabeth Smyth, MD, FRCP - When They Need More Than Trastuzumab: Deciding on What's Next for Patients With HER2+ Gastric Cancer

Elizabeth Smyth, MD, FRCP - When They Need More Than Trastuzumab: Deciding on What's Next for Patients With HER2+ Gastric Cancer

Our first story highlights Odin Medical's FDA clearance for a cloud-based AI tool for detecting colorectal polyps during colonoscopies. The second story addresses updated estimates of atrial fibrillation (AF) prevalence in the U.S., revealing a significant increase in diagnosed cases, especially among younger, hypertensive, and diabetic patients. Finally, we explore new data on the the efficacy of Trastuzumab deruxtecan (T-DXd) in treating HER2+ metastatic breast cancer.

Did you miss the ESMO Congress 2024? Listen here: NEJM Editor-in-Chief Eric Rubin and NEJM Evidence Associate Editor Oladapo Yeku discuss research that was presented at the 2024 European Society of Medical Oncology annual meeting. Visit NEJM.org to read the latest research.

Dr Kanwal Raghav (Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA) discusses his Article entitled, ‘Trastuzumab deruxtecan in HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a randomised, multicentre, phase 2 trial'.Read the full article:https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00380-2/fulltext?dgcid=buzzsprout_icw_podcast_generic_lanoncTell us what you thought about this episodeContinue this conversation on social!Follow us today at...https://twitter.com/thelancet & https://Twitter.com/TheLancetOncolhttps://instagram.com/thelancetgrouphttps://facebook.com/thelancetmedicaljournalhttps://linkedIn.com/company/the-lancethttps://youtube.com/thelancettv

Drs. Claudine Isaacs and Filipa Lynce continue their discussion on the highlights of ASCO 2024 Annual Meeting, with a focus on HER2+ breast cancer. In part two of the discussion, the focus is on two studies pertaining to HER2-positive breast cancer. The first study, the GBCRG-M06 Emerald Study compared the effectiveness and toxicity of eribulin mesylate versus a taxane (with trastuzumab and pertuzumab) in a first-line treatment setting. The study, involving approximately 450 patients, found similar progression-free survival (PFS) between the taxane backbone (13 months) and the eribulin backbone (14 months). However, there was slightly more peripheral neuropathy observed with eribulin. The second study discussed is the Patricia study (cohort C) investigating the use of CDK4-6 inhibitors combined with trastuzumab and endocrine therapy in ER-positive, HER2-positive breast cancer patients who had progressed on prior HER2-targeted therapies. The study indicated an improved PFS with the introduction of CDK4-6 inhibitors (9 months) compared to the control arm (7.5 months). The discussion also anticipates the results of the ongoing PATINA study, which looks to determine whether adding CDK4-6 inhibitors during maintenance therapy will benefit patients with advanced ER-positive, HER2-positive breast cancer.

This is the first of the three-part podcast series, Keeping up with the Chemos on Trastuzumab Deruxtecan ENHERTU®. After going over some general information on Trastuzumab Deruxtecan ENHERTU® including when to use the drug, checking patient performance status, toxicity, response rates in breast, and line of therapy and treatment option. The multidisciplinary panel will discuss dosing and drug preparation for giving Trastuzumab Deruxtecan ENHERTU®. The session wraps up with some key take home points on Trastuzumab Deruxtecan ENHERTU®.  2023-2024 SGO Chemotherapy and Targeted Therapies Subcommittee Member and Moderator:Tracilyn Hall, MDSpeakers:Jennifer MacDonald, PharmD, BCOPKathleen Moore, MDBernard Tawfik, MD 

This is the second of the three-part podcast series, Keeping up with the Chemos on Trastuzumab Deruxtecan ENHERTU®.  Our multidisciplinary panel will discuss the important information about the drug preparation and administration of Trastuzumab Deruxtecan ENHERTU®.  Focusing on dosing, breast scoring, HER2, infusion reactions, lab examinations, and patient education. The session ends with general take home points on administration and toxicity prevention interventions.2023-2024 SGO Chemotherapy and Targeted Therapies Subcommittee Member and Moderator:Tracilyn Hall, MDSpeakers:Jennifer MacDonald, PharmD, BCOPKathleen Moore, MDBernard Tawfik, MD 

This is the last of the three-part podcast series, Keeping up with the Chemos on Trastuzumab Deruxtecan ENHERTU®. Our multidisciplinary panel will discuss the challenges with patient monitoring while on Trastuzumab Deruxtecan ENHERTU®. When to dose adjust and hold or even discontinue Trastuzumab Deruxtecan ENHERTU®. Once again, the podcast ends with take home points for patient monitoring and side effects while on Trastuzumab Deruxtecan ENHERTU®.  2023-2024 SGO Chemotherapy and Targeted Therapies Subcommittee Member and Moderator:Tracilyn Hall, MDSpeakers:Jennifer MacDonald, PharmD, BCOPKathleen Moore, MDBernard Tawfik, MD 

Data from the DESTINY Breast06 trial using the antibody-drug conjugate trastuzumab deruxtecan to treat patients with estrogen receptor positive (HR+), human epidermal growth factor receptor-low (HER2-low), and HER2-ultralow breast cancer after endocrine therapy, show longer progression-free survival in comparison with standard chemotherapy. After announcing the results at the 2024 ASCO Annual Meeting, first author Giuseppe Curigliano, MD, PhD, Director of Early Drug Development for the Innovative Therapies Division of the European Institute of Oncology, discussed the findings with Oncology Times correspondent Peter Goodwin

Following the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Neil M. Iyengar, MD, and Paolo Tarantino, MD, co-hosted a live X Space with CancerNetwork® and discussed the latest trial updates that may impact clinical practice in the breast cancer field. Iyengar is an associate attending physician at Memorial Sloan Kettering Cancer Center and a co-editor-in-chief of ONCOLOGY®. Tarantino is a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School.  Iyengar and Tarantino discussed data regarding several trials and studies presented at the meeting. These presentations included:  ·      Phase 3 DESTINY-Breast06 Trial (NCT04494425)1 o   Investigators evaluated treatment with trastuzumab deruxtecan (T-DXd; Enhertu) compared with investigator's choice of chemotherapy among patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow metastatic breast cancer. o   The median progression-free survival (PFS) was 13.2 months with T-DXd compared with 8.1 months in patients who received chemotherapy across the HER2-low population (HR, 0.62; 95% CI, 0.51-0.74; P

Listen to a soundcast of the April 5, 2024, FDA approval of Enhertu (fam-trastuzumab deruxtecan-nxki) for unresectable or metastatic HER2-positive solid tumors.

ChatGPT4 in medical writing and editing at learnAMAstyle.com Nascentmc.com for medical writing assistance for your company. Visit nascentmc.com/podcast for full show notes Tricuspid Valve Replacement System for Tricuspid Regurgitation The FDA approved the Evoque tricuspid valve replacement system, a first in the U.S. for a transcatheter tricuspid device, after the TRISCEND II trial showed significant improvements in TR grade and patient symptoms. TR, where the heart's valve does not close properly causing blood backflow, can now be treated with this device, which also received CE Mark approval in Europe and is produced by Edwards Lifesciences. Afami-Cel for Synovial Sarcoma The FDA is prioritizing the review of afamitresgene autoleucel (afami-cel) for advanced synovial sarcoma, based on positive results from the SPEARHEAD-1 trial showing a 39% response rate and increased survival rates. Afami-cel targets MAGE-A4 in synovial sarcoma, a rare soft tissue sarcoma, offering a new treatment option for this aggressive disease. It's manufactured by Adaptimmune Therapeutics with a decision expected by August 4, 2024.  Pulsed Field Ablation for Atrial Fibrillation Boston Scientific's FARAPULSE PFA System has been FDA approved for treating intermittent atrial fibrillation, offering a non-thermal, tissue-selective ablation alternative with proven safety and efficacy. The approval was based on the ADVENT study and real-world data, highlighting shorter ablation times and no severe side effects. Boston Scientific plans an immediate U.S. launch. Shorter Turnaround Time for Axi-cel The FDA approved a manufacturing process change for axi-cel (Yescarta), reducing delivery time from 16 to 14 days, which is a CD19-directed CAR T-cell therapy for certain lymphomas. This change, granted to Kite, a Gilead Sciences subsidiary, aims to improve treatment accessibility by offering faster delivery of this personalized therapy. AI Algorithm for Cervical Cancer Screening Hologic's Genius™ Digital Diagnostics System with the Genius™ Cervical AI algorithm has been FDA approved, introducing the first digital cytology platform integrating AI for cervical cancer screening. This system digitizes traditional Pap test slides, applying AI to enhance detection of pre-cancerous and cancerous cells, improving sensitivity and enabling remote case review. It will be available in the U.S. in early 2024. Trastuzumab Deruxtecan for Solid Tumors The FDA granted priority review to trastuzumab deruxtecan for treating unresectable or metastatic HER2-positive solid tumors, potentially marking it as the first HER2-directed, tumor-agnostic therapy. Based on the DESTINY-PanTumor02 study, showing promising survival outcomes, a decision is expected in the second quarter of 2024. The drug is developed by AstraZeneca and Daiichi Sankyo.  

In discussion with Dr. Daniel G. Stover, covering the San Antonio Breast Cancer Symposium 2023 Highlights from Community Oncology perspective. We covered 3 important practice informing studies in HER2+ disease with Dr. Stover: - APHINITY Sub-analysis: Benefit of Adj Pertuzumab and Trastuzumab According to ER and HER2 Expression - KATHERINE Update: Phase III Study of Adjuvant TDM-1 vs Trastuzumab for Residual Invasive HER2-positive Early Breast Cancer After Neoadj Chemo: Final IDFS and Updated OS analysis - HER2CLIMB-02: Randomized, Double-blind Phase 3 Trial of Tucatinib and TDM1 for Previously Treated HER2-positive Metastatic Breast Cancer

Featuring an interview with Dr David M O'Malley, including the following topics: Prevalence of HER2 positivity among various gynecologic cancer subtypes; current testing recommendations (0:00) Trastuzumab and other HER2-targeted therapies as a component of treatment for HER2-positive gynecologic cancers (15:17) Key efficacy outcomes achieved with trastuzumab deruxtecan (T-DXd) among patients with advanced ovarian, endometrial and cervical cancers in the DESTINY-PanTumor02 study (18:05) Incidence of interstitial lung disease (ILD) and other toxicities with T-DXd in the DESTINY-PanTumor02 trial; strategies to manage ILD associated with HER2-directed antibody-drug conjugates (27:59) Case: A woman in her mid-60s with HER2-low (IHC 1+) recurrent uterine carcinosarcoma receives T-DXd on a clinical trial (34:26) Case: A woman in her mid-70s with recurrent uterine serous cancer and history of Crohn's disease (51:05) Case: A woman in her mid-60s with Stage IIIC primary uterine serous cancer receives carboplatin/paclitaxel/trastuzumab followed by maintenance trastuzumab with no evidence of disease 4 years later (56:50) CME information and select publications

Last Wednesday, Pharmac confirmed it would be replacing treatment Herceptin (brand name for the drug Trastuzumab) with Herzuma, another version of the drug which is equally as effective but at a lower cost. Pharmac has decided not to provide more retreatment opportunities for patients with advanced HER2-positive breast cancer, but Breast Cancer Foundation New Zealand is urging them to reconsider. Rosetta spoke to Adele Gautier, Research and Strategic Programmes Manager for BCFNZ about the decision, and what more needs to be done to increase retreatment options in Aotearoa.

Although T-DXd had already been licensed for use in all categories of HER2 positivity, including patients with so-called HER2-low tumors (defined as having immunohistochemical score of 1+ or 2+ with non-amplified in-situ hybridization), doubts have remained about the effectiveness of this antibody drug conjugate in the subset of such patients who also have low expression of the estrogen receptor, ER (having ER expression from 1-10%). At the ESMO Breast Cancer 2023 conference a sub-study analysis of the DESTINY-Breast04 Phase III study was reported that specifically addressed this topic. OncTimesTalk reporter, Peter Goodwin, asked David Cameron, MD, about his group’s findings on the effectiveness of T-DXd in ER-low metastatic breast cancer, and about the context and overall potential of using antibody drug conjugates in breast cancer. Cameron is Professor of Oncology at Edinburgh University and a joint lead for the Edinburgh Experimental Cancer Medicine Centre.

JCO PO author Dr. Apar K. Ganti shares insights into his JCO PO article, “Pertuzumab Plus Trastuzumab in Patients With Lung Cancer With ERBB2 Mutation or Amplification: Results From the Targeted Agent and Profiling Utilization Registry Study.” Host Dr. Rafeh Naqash and Dr. Ganti discuss clinical decision-making regarding biopsy; HER2 amplification, mutation, and targeted therapy; drug combinations; and aspects of the TAPUR and DESTINY-Lung studies. Click here to read the article!   TRANSCRIPT Dr. Abdul Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Abdul Rafeh Naqash, Social Media Editor for JCO Precision Oncology, and Assistant Professor at the University of Oklahoma Stephenson Cancer Center.  Today we are joined by Dr. Apar Kishor Ganti. Dr. Ganti is a Professor of Medicine and associate director of clinical research at the Fred and Pamela Buffett Cancer Center at the University of Nebraska Medical Center. He's also a staff physician at the VA Nebraska Western Iowa Healthcare System. Dr. Ganti is the lead author of the JCO Precision Oncology article titled "Pertuzumab Plus Trastuzumab in Patients With Lung Cancer With ERBB2 Mutation or Amplification: Results From the Targeted Agent and Profiling Utilization Registry Study," which is also the TAPUR Study.  Dr. Ganti, thank you so much for joining us today. Dr. Apar Kishor Ganti: Thank you for having me. I'm happy to be here. Dr. Abdul Rafeh Naqash: For starters, Dr. Ganti, this is one of the trials from the TAPUR Basket study. So I wanted to take this opportunity since this is an ASCO initiative that has been there for a few years now. Could you tell us a little bit of background about the TAPUR initiative, what kind of trials are being run or have been run, and how it all started, basically?  Dr. Apar Kishor Ganti: The TAPUR Study or the Targeted Agent and Profiling Utilization Registry Study is a pragmatic basket trial which evaluates the anti-tumor activity of commercially available targeted agents in patients with advanced cancers and tumors that have potentially actionable genomic alterations, like mutations, amplifications, etc. And this has multiple arms in multiple malignancies, using drugs that are currently approved in different indications and not necessarily approved for the indication that's being studied. But there's preclinical data that suggests that that particular drug may potentially be active in patients whose tumors harbor those mutations. For example, this present study that we conducted utilized a combination of pertuzumab and trastuzumab, both of which are FDA-approved for the treatment of patients with HER2-positive breast cancers. And we analyzed the efficacy of the combination of these two drugs in patients with lung cancer who had either a HER2 mutation or an amplification of HER2.  Dr. Abdul Rafeh Naqash: Thank you so much for giving us that background. Going to this study specifically, which is one of the very interesting TAPUR studies, what I'm reminded of especially is NCI-MATCH, for example, which runs on a similar premise to this study, where we've seen some successes and some not as exciting combination approach successes that is what we would have wanted to see.  For lung cancer specifically, as you and I both know and perhaps many of the listeners know, there's a lot of actionable drivers that have target therapies that are approved, could you touch on some of those to give a background on where the field currently lies and what are some of the important steps with respect to obtaining next generation sequencing, perhaps in patients. So what your practice is and what you would recommend for these individuals? Dr. Apar Kishor Ganti: Certainly, non-small cell lung cancer, or non-squamous non-small cell lung cancer, to be more precise, seems to be the poster child for next-generation sequencing. And the importance of NGS testing cannot be overemphasized in these patients. For example, right now we have multiple different drivers that have drugs approved for the management of these patients. The first among them, obviously, was EGFR or epidermal growth factor receptor. And that has been followed fairly successfully by targeting ALK, ROS1, now, more recently, RET, MET, KRAS, and HER2. So if you look at lung adenocarcinomas, almost half of the patients will have a tumor with a mutation that is targetable. And so it's very important to make sure that these patients are tested for, before initiating any therapy. What makes it more important is that the standard of care for patients with non-small cell lung cancer without driver mutations is either immunotherapy or chemoimmunotherapy. And we have found that if a patient has a driver mutation, especially EGFR or ALK, even if their PD-L1 expression is extremely high, their response to checkpoint inhibitors is negligible. And so it is important to make sure that we understand what their molecular status is before starting any treatment in these patients. And I think the key point here is that every patient with advanced non-small cell lung cancer should have next generation sequencing studies done prior to initiation of treatment. Dr. Abdul Rafeh Naqash: Absolutely. And in your practice, Dr. Ganti, do you tend to do liquid biopsies concurrently when you get a new individual with a diagnosis of lung cancer, or do you do it at some other time point?  Dr. Apar Kishor Ganti: Liquid biopsies, I tend to get them, but not as frequently as some would like. I tend to believe more in tumor biopsies, and I would get liquid biopsies only in the setting where a tumor biopsy is not feasible or if I feel that the patient needs treatment more rapidly than can be expected if I got a tissue biopsy. Liquid biopsies, in my opinion, are good, but they're very dependent on the tumor fraction that is present in the sample that you send. As you very well know, not all patients who have a driver mutation necessarily shed the mutation into the blood. And therefore, even if a patient has a driver mutation in a tumor, there is a small chance that the liquid biopsy may not detect it. So I tend to be more in favor of getting tumor biopsies for next-generation sequencing. In situations where the tumor fraction is high, the concordance between tumor biopsies and liquid biopsies is fairly good. Dr. Abdul Rafeh Naqash: Thank you so much for that very important clinical decision-making thought process. At least in my practice, when tissue is often the issue, as you very well know, where you don't either have enough tumor cells or the biopsy is just enough to tell you whether it is squamous or non-squamous and not enough for any further sequencing, I try to get liquid biopsies whenever feasible and appropriate so that at least we can rule out some of the driver alterations before I put a patient on immunotherapies, due to the concern for subsequent toxicities if there are driver alterations. But I totally agree, I think tissue is definitely the standard, gold standard. And if you have overlapping mutations in tissue and liquid, then obviously it increases your confidence of treating that individual with that targeted therapy. But in general, tissue definitely, at least we should try to emphasize, and I try to do this often when I get a call from a community oncologist. I'm pretty sure you do the same where we ask for multigene broad gene testing NGS, so that especially when you have HER2 mutations, for example, you won't necessarily capture those as you show on your study here.   Now, going to your study, Dr. Ganti, could you tell us a little bit more about HER2 mutations and amplifications? And there's different levels of evidence where amplification may not lead to expression or expression may not lead to amplification. And then there is a separate category of HER2 mutations. And a lot of what we know for HER2 is from breast cancer. And recently, in the last two to three years now, is for lung cancer also. Could you tell us about how the field is shaping from a HER2 mutational landscape, an amplification landscape, in the lung cancer field?  Dr. Apar Kishor Ganti: As you rightly said, most of our knowledge from HER2 is from the breast cancer world. And frankly, I think we've been spoiled by the data on breast cancer. So, unlike in breast cancer, lung cancer seems to have a much lower frequency of HER2 alterations. And while in breast cancer, HER2 amplification seems to be important and predictive for response to HER2-targeted agents, in lung cancer, we see a combination of mutations and amplifications. So, in a large TCGA study, mutations in HER2 seem to occur in about 2% of all lung cancers. And amplification seems to be occurring in approximately a similar proportion of different patients. So, they seem to be mutually exclusive as best as we can tell.  And, unlike in breast cancer, where HER2 amplification seems to be directly associated with protein over-expression and response to tumor, the data in lung are much less robust. And so, it is not necessarily that an amplification will translate into a prediction of response to a HER2-targeted agent. And we and certain other studies have shown that patients who have HER2 amplification may not respond as well to HER2-targeted therapy as opposed to, for example, patients with HER2 mutations. So, that seems to be the discrepancy in HER2 amplification and HER2 mutations when you look at lung cancer versus breast cancer. And that's another reason why we are doing the TAPUR study at the various arms because what works in one specific cancer with the same mutation or same abnormality may not necessarily work in other cancers. Dr. Abdul Rafeh Naqash: Absolutely. Thank you for indulging into that side of things. Now, going back to your trial, could you tell us a little bit of background on the eligibility criteria, how you chose some of the different mutations? What were the levels of evidence for some of those mutations from a pathogenicity standpoint, and then what were your endpoints, since this is a clinical trial with a Simon two-stage design?  Dr. Apar Kishor Ganti: Patients who were eligible for the trial included all patients with advanced lung cancer who did not have another FDA-approved treatment or were not candidates for another treatment. They all should have been 18 years or older at the time of diagnosis and have lung cancer with either ERBB2 amplification or we looked at 13 specific mutations, insertions, or deletions, and, if the patient had any of those abnormalities identified by any clear approved next-generation sequencing testing platform, then they would be eligible for the study. We chose these because of how frequently these specific mutations occurred in lung cancer and other cancers. And so, these 13 abnormalities were chosen from the host of HER2 mutations that you can see. Patients should not have received a previous HER2 inhibitor, obviously, and their LV ejection fraction should be normal because of the known risk of decreasing cardiac function with HER2-targeted therapy. They were treated with pertuzumab every three weeks and then combined with trastuzumab. Trastuzumab was given at a loading dose, initially of 8 milligrams per kilogram, and in subsequent cycles, we used 6 milligrams per kilogram. The dose of pertuzumab was a flat dose of 840 milligrams for the first dose and 420 milligrams for subsequent doses.  We continued the treatment till progression or excessive toxicity or patient withdrawal of consent. The endpoints were disease control, which we defined as objective response or stable disease for at least 16 weeks duration. Other endpoints were progression-free survival, overall survival, duration of response, and, of course, safety. We used a Simon two-stage design, as you said. The null hypothesis was that the disease control rate would be 15%, alternative hypothesis was 35%, the power was 85%, alpha was at 10%. So, if in the first stage, less than two out of ten patients had disease control, then the cohort would be closed for futility. If two patients or more had disease control of the first 10, then we expanded to an additional 18 patients for a total study size of 28. So, as far as safety analysis, any patient who received even a single dose of treatment was included in that safety analysis.  Dr. Abdul Rafeh Naqash: Thank you so much for giving us those details about the cohort. Going to the mutation or the amplifications, I'm looking at the cohort, so it seems like more or less, to some extent, there was an equal distribution of the mutations. 50% of individuals had mutations and then around 45%, 43% had amplifications. Did that play into your expectation of how the cohort did in terms of responses or the primary endpoints that you had set? Did you see differences based on those findings of mutations versus amplifications.  Dr. Apar Kishor Ganti: Yes, we did. The disease control rate was 37%, with an overall response rate of 11%. And when you looked at patients who had a partial response, which is three patients, all of them had ERBB2 mutation. And of the patients who had stable disease, only two patients out of seven had an amplification. Five patients had the mutation. So, again, this was similar to what we had expected, that based on previous studies, patients with mutation tend to respond better than patients with alterations. Dr. Abdul Rafeh Naqash: Definitely. And going to one of the striking figures that you have in this manuscript, of course, you have the waterfall plot, and then you have the swimmer's plot and the spider plot. I'm very intrigued personally by the spider plot, which is the Figure 3 in your paper, especially with this individual that had this long, durable partial response. I believe this was the same individual with the mutation. I believe it was this 776 insertion. Was there anything, any other aspect that could have contributed to this response, or does this mutation, does it have any strong preclinical data of why the activity offer to direct therapy might be more pronounced in this mutation that you came across?  Dr. Apar Kishor Ganti: Not to my knowledge. I don't think we found anything specific or different about this particular patient compared to the others. So, as far as the mutation itself is concerned, it's a fairly common mutation, the G776 insertion. It is one of the most common mutations seen in lung cancer, and studies have shown that patients with the mutation tend to respond. But why this patient responded so long, it's difficult to say. I wish we were able to find out, but unfortunately, we were not able to. Dr. Abdul Rafeh Naqash: Sure. Another question that I wanted to ask you since this falls into the precision medicine basket study questions. Does TAPUR have a different endpoint for different sub-studies? Because I vaguely remember coming across another paper where I believe a 16-week disease control was also the endpoint. So, is that something universal in TAPUR, or is it specific for specific tumor types and different combination approaches? Dr. Apar Kishor Ganti: I believe that this is a more generalized feature of the TAPUR study, the stable disease for 16 weeks as a marker of response. Of course, different arms have additional endpoints, but I think this is one of the more common ones. Dr. Abdul Rafeh Naqash: Now, there has been some work, as you very well pointed out in your paper as well, from others related to HER2 mutations, especially the DESTINY-Lung study. Could you tell us a little bit about that for listeners who may not be well aware of the DESTINY study with trastuzumab deruxtecan targeting the HER2 mutations? Dr. Apar Kishor Ganti: So, DESTINY-Lung01 was a study of patients with ERBB2 mutated lung cancer. That study just looked at mutation-positive patients as opposed to what we did, looking at both mutation and amplification. And that study showed an overall response rate of 55%, which was much higher and led to the approval of fam- trastuzumab-deruxtecan in this group of patients. And so, one of the differences between our study and trastuzumab deruxtecan DESTINY-Lung01 study, is that our study included patients with both mutations and amplification and our study did not include any cytotoxic drug. And I believe that was one of the big differences, which may make the results of our study intriguing and potentially useful to patients who may not be able to tolerate a cytotoxic agent. Because, as you know, fam-trastuzumab-deruxtecan has the cytotoxic binder. It's an ADC and has been known to have some toxicities. And the thing about lung cancer is that these patients are relatively frail and may not be able to tolerate it. And so, that's one of the major differences, a portion at least for this combination, even though the response rates are much smaller than what we see with fam-trastuzumab-deruxtecan. Dr. Abdul Rafeh Naqash: And from your practice, have you started using this combination from your study as a potential approach for individuals who may not be candidates for trastuzumab deruxtecan in your clinic? Dr. Apar Kishor Ganti: I have not as yet because I have not come across a patient who would be eligible for this combination. In my practice, as we have TAPUR open, we have the tucatinib-trastuzumab arm that opened after this arm closed. So my priority is to try and enroll patients onto that cohort. And so I currently have one patient on that. And as you know, this is not a very common alteration, so we don't have as many patients with this. But definitely, this would be a combination that I would put patients on if I felt that they were not a candidate for fam-trastuzumab-deruxtecan.  Dr. Abdul Rafeh Naqash: So, Dr. Ganti, what's the next step after this since your study didn't meet some of its endpoints? What are you planning, or is there a plan to expand on this through the TAPUR mechanism?   Dr. Apar Kishor Ganti: Right now, I don't think that there's a mechanism through TAPUR to expand this particular cohort because there is also another cohort that opened subsequently with tucatinib and trastuzumab. But I think it would not be unreasonable to study this combination in patients who are not candidates for fam-trastuzumab because of the differences in toxicity. So that would be where I would potentially see a role for this particular combination, and I think it should be studied in that setting. Dr. Abdul Rafeh Naqash: Excellent. Now, I try to dedicate a section of this conversation for provocative discussions that may not be addressed in your paper, but I still like to get insights from experts in the field such as yourself. So comparing it to the NCI-MATCH or some other precision medicine-based initiatives, we do often see that mutations that we think might be driving the process don't necessarily lead to really high or really promising responses to targeted therapies. So in this case, do you think, from a futuristic standpoint, a proteomic-based assay, since I think you work in the proteomic space as well, that would be an interesting way to look at whether signaling actually is altered from a mutation or an amplification, suggesting that that is driving the process, so would be a more attractive target than just looking at a mutational signature?  Dr. Apar Kishor Ganti: I think definitely that should be the way we should be looking at these kinds of studies, because even in this study, even if you look at fam-trastuzumab-deruxtecan and the DESTINY-Lung01 study, we have patients who have definite, identified drivers, and even there, only about half of the patients responded. It was much smaller in our study. But basically what I'm getting at is with the best of the drugs that we have today, only half of our patients respond with HER-2 mutations, for example. So I would definitely favor a more integrated approach to identifying those patients who would be candidates for these targeted agents and not just simply relying on a specific mutation.  Since we are being provocative, I would go one step further and say, “Hey, we have AI. And there are currently AI-based technologies which look at the entire next-generation sequencing profile and try to identify which drugs could potentially be effective in those patients based on a complete understanding of their entire tumor genetic profile, rather than just looking at one or two, or three mutations.” So that, I think, would be a much more robust approach through precision medicine. So, like you just said, that patient that we had who had a prolonged response, we don't know why he or she had a prolonged response. And maybe if we identified a pathway or pathways which were overexpressed or more active in that particular tumor setting, we would be able to identify better targets and better approaches for those patients. So I think that is the way to go in the future. Dr. Abdul Rafeh Naqash: Excellent. Thanks for indulging into that provocative discussion and hopefully maybe five years down the line when we meet again or run across each other at ASCO, we will say, “Oh, it did actually happen, that multiomics is being used in a way that is suited for the need of the patient.” So matching the right patient to the right therapy at the right time.  So, Dr. Ganti, the last section is going to be dedicated to you as an individual. So you've had a very successful, brilliant career as a clinical trialist and as a lung cancer expert. Tell us, for the sake of our listeners and perhaps some of the early career junior investigators, what your career trajectory has been briefly, and what are some of the things that you felt were successful that could provide advice and insights to people who are earlier in their careers and trying to emulate what perhaps you have done or you are doing?  Dr. Apar Kishor Ganti: Well, that is a big one. I never thought of myself as being a role model for anyone, far less someone who's at the beginning of their career. But what I have always mentioned to students and residents and fellows is basically there is no substitute for hard work. Luck plays some role in this because you need to be at the right place at the right time for some of it, but hard work definitely will pay off. And the other thing that is important is not to get disheartened if your first clinical trial gets rejected or concept gets rejected, or if your first grant gets unscored. That is part of life, and persisting is probably the best way to continue.   Also, continuing to believe in yourself. I've seen a lot of folks, especially once they get into their second or third year after fellowship when things are not going the way they want to, they start to wonder, “Am I suited for this job? Am I the right person? Am I doing this correctly? Should I be doing something else?” And I think it's just a matter of time before they will find success. And also, the other thing is, if one particular approach does not work, there are always other ways that you can look at. So, for example, if you extend a bunch of clinical trial concepts that do not work out, you could potentially look at other ways of answering questions. For example, you could do retrospective analyses, come up with provocative, hypothetical generating questions that could be answered in the future in a prospective study. So there are lots of avenues to do that. And I think I was benefited by my mentors who helped me see this relatively early in my career. Dr. Abdul Rafeh Naqash: Thank you so much, Dr. Ganti, for all those valuable insights that you've learned over your career and hopefully will help some of the listeners. Before we finish, I'm going to ask you three rapid-fire questions that hopefully will let our listeners--give them a little bit of a sneak peek into you as a person. And you get like five seconds for each question. And they're not complicated questions. My first question to you is what is your favorite food? Dr. Apar Kishor Ganti: Thai food. Dr. Abdul Rafeh Naqash: What is your favorite place to go for vacation?  Dr. Apar Kishor Ganti: South Africa.  Dr. Abdul Rafeh Naqash: And what is your favorite hobby?  Dr. Apar Kishor Ganti: Reading.  Dr. Abdul Rafeh Naqash: Well, thank you so much again, Dr. Ganti. This was a very interesting conversation and hopefully, when you or others have other TAPUR-related trial results, perhaps they will again choose JCO PO as a destination for that work.  Thank you for listening to JCO Precision Oncology Conversations. 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/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. 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.   Guest Bio: Dr. Apar Kishor Ganti, MD, MS, is professor of medicine and Associate Director of Clinical Research, Fred & Pamela Buffett Cancer Center at the University of Nebraska Medical Center and Staff Physician at VA Nebraska Western Iowa Health Care System.   Guest COIs: Apar Kishor Ganti, MD, MS Consulting or Advisory Role: AstraZeneca, Jazz Pharmaceuticals, Flagship Biosciences, Cardinal Health, Sanofi Genzyme, Regeneron, Eisai Research Funding: Apexigen (Inst), NEKTAR Pharmaceuticals (Inst), TopAlliance BioSciences Inc (Inst), Novartis (Inst), Iovance (Inst), Mirati Therapeutics (Inst), Chimeric Therapeutics (Inst)  

Dr. Iyad Alnahhas interviews Drs. Priya Kumthekar and Jeffrey Raizer about their recent manuscript entitled: A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2- positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics", published online in Neuro-Oncology in March 2023.

CME credits: 1.00 Valid until: 17-07-2024 Claim your CME credit at https://reachmd.com/programs/cme/who-is-the-best-candidate-for-sequencing-trastuzumab-detruxtecan-t-dxd-first/15793/ This program explores new evidence that challenges the binary paradigm of HER2+ versus HER2- disease. Evidence is now available that specific antibody-drug conjugates (ADCs) have demonstrated benefit not only in HER2+ disease but also in a new group of “HER2-low” patients. Clinicians will learn how to reframe their diagnostic and treatment paradigms, moving from a siloed view to a more nuanced assessment of breast cancer characteristics. Episodes will provide a greater understanding of how ADC targets and payloads, such as HER2 and Trop-2 can significantly improve a patient's quality of life and extend their survival by increasing the pool of patients who may now benefit from ADCs. Aspects of diagnosing, treatment, and sequencing are discussed so that clinicians better understand how current and emerging ADCs address the unmet needs of patients with pretreated metastatic disease. Video education created for patients is available for this topic. Visit www.mymededge.com to “prescribe” education that helps patients and caregivers learn more about this condition.

Join Drs Stanley Cohen and Jonathan Kay as they discuss biosimilars in PsA, which will hit the US market this summer. They cover everything from working with your pharmacy to counseling patients. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984272). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Psoriatic Arthritis https://emedicine.medscape.com/article/2196539-overview Biosimilars for the Treatment of Psoriatic Arthritis https://pubmed.ncbi.nlm.nih.gov/31625769/ Biosimilars and the Extrapolation of Indications for Inflammatory Conditions https://pubmed.ncbi.nlm.nih.gov/28255229/ Adalimumab (Rx) https://reference.medscape.com/drug/amjevita-humira-adalimumab-343187 Comparison of Skindex-29, Dermatology Life Quality Index, Psoriasis Disability Index and Medical Outcome Study Short Form 36 in Patients With Mild to Severe Psoriasis https://pubmed.ncbi.nlm.nih.gov/22229951/ Infliximab (Rx) https://reference.medscape.com/drug/remicade-inflectra-infliximab-343202 Rituximab (Rx) https://reference.medscape.com/drug/rituxan-truxima-rituximab-342243 Subcutaneous Injection of Drugs: Literature Review of Factors Influencing Pain Sensation at the Injection Site https://pubmed.ncbi.nlm.nih.gov/31587143/ Biosimilars to Bring a Bumper Crop of Adalimumab Options https://www.centerforbiosimilars.com/view/part-1-biosimilars-to-bring-a-bumper-crop-of-adalimumab-options The Difference Between an Interchangeable Biosimilar and One That Isn't https://www.centerforbiosimilars.com/view/the-difference-between-an-interchangeable-biosimilar-and-one-that-isn-t The Non-Medical Switching of Prescription Medications https://pubmed.ncbi.nlm.nih.gov/31081414/ Implementation of the Biologics Price Competition and Innovation Act of 2009 https://www.fda.gov/drugs/guidance-compliance-regulatory-information/implementation-biologics-price-competition-and-innovation-act-2009 Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer https://pubmed.ncbi.nlm.nih.gov/36009592/ Certolizumab pegol (Rx) https://reference.medscape.com/drug/cimzia-certolizumab-pegol-343185

Listen in to this podcast recorded live at the American Society of Clinical Oncology (ASCO) Annual Meeting With Funda Meric-Bernstam, MD

High Yield Breast Cancer Review.Review for your PANCE, PANRE, Eor's and other Physician Assistant exams. Merchandise Link: https://cram-the-pance.creator-spring.com/►Paypal Donation Link: https://bit.ly/3dxmTql (Thank you!)Included in review: Breast cancer risk factors, clinical manifestations, physical exam findings, screening, diagnostic tools including mammogram, ultrasound, fna, core needle biopsy, surgical biopsy, Paget disease of the breast, Inflammatory breast cancer, In situ, Invasive, Infiltrating ductal carcinoma, HER2 positive, hormone receptor positive, Tamoxifen, Trastuzumab, targeted therapy, chemotherapy, radiation.

Featuring perspectives from Drs Eric Lee, Neil Morganstein and Swati Vishwanathan, including the following topics: •      Gastroesophageal Cancers — Zev Wainberg, MD, MSc  o   Introduction (0:00) o   Systemic therapy considerations for HER2-negative localized gastroesophageal cancers (4:33) o   First-line systemic therapy for metastatic esophageal or gastric cancer (10:05) o   Zolbetuximab/chemotherapy as first-line treatment for HER2-negative, locally advanced unresectable or metastatic gastric and gastroesophageal junction cancers (16:19) o   Repeat tissue biopsy versus circulating tumor DNA testing for HER2-positive GI cancers after disease progression on first-line therapy (20:59) o   Trastuzumab deruxtecan as second-line therapy for HER2-positive gastric cancer; management of CNS disease (25:05) •      Hepatobiliary Cancers — Lipika Goyal, MD, MPhil  o   Tissue biopsy for suspected hepatocellular carcinoma (HCC) (29:59) o   Atezolizumab/bevacizumab versus durvalumab/tremelimumab as first-line therapy for HCC; disease etiology and response to treatment (33:34) o   Liver-directed therapy in the era of effective novel systemic regimens (40:50) o   First-line, single-agent immunotherapy for HCC (44:33) o   Sequencing tyrosine kinase inhibitors for patients with HCC with and without contraindications to immunotherapy (47:46) o   Survival benefit with durvalumab/gemcitabine/cisplatin for advanced biliary tract cancers (BTCs) in the TOPAZ-1 trial — A new standard? (51:25) o   Spectrum of targetable genetic alterations in BTCs; novel FGFR2 inhibitors for cholangiocarcinoma (54:28) CME information and select publications

Discussing the MOUNTAINEER Phase II study, which resulted in the FDA approval of the Tucatinib and Trastuzumab combination for advanced colorectal cancer HER2 positive patients. In discussion with the lead author, Dr. Tanios S. Bekaii-Saab - Medical Oncology Chief, Leader of Enterprise Wide GI Cancer Program at Mayo Clinic Comprehensive Cancer Center.     Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

Listen to a soundcast of the January 19, 2023, FDA approvals of Tukysa (tucatinib) with trastuzumab for colorectal cancer and Brukinsa (zanubrutinib) for chronic lymphocytic leukemia or small lymphocytic lymphoma.

Dr Strickler discusses the FDA approval of tucatinib plus trastuzumab in metastatic colorectal cancer, key efficacy and safety findings from the MOUNTAINEER trial, and ongoing research seeking to address remaining unmet needs in this population.

Dr. Filip Ionescu (hematology-oncology fellow at Moffitt Cancer Center in Tampa, FL), Dr. Teodora Donisan (cardiology fellow at the Mayo Clinic in Rochester, MN and CardioNerds House Thomas chief), Dr. Sarah Waliany (internal medicine chief resident at Stanford University in Palo Alto, CA), Dr. Dinu Balanescu (internal medicine chief resident at Beaumont Hospital in Royal Oak, MI) and Dr. Amit Goyal (structural interventional cardiology fellow at the Cleveland Clinic, in Cleveland, OH and CardioNerds Co-Founder), discuss the cardiotoxicities of common cancer treatments with Dr. Susan Dent, a medical oncologist and one of the founders of the field of Cardio-Oncology. Using the recently published ESC Guidelines on cardio-oncology, they cover cardiovascular risk stratification in oncology patients, pretreatment testing, as well as prevention and management of established cardiotoxicity resulting from anthracyclines, trastuzumab, and fluoropyrimidines. They touch on the unique aspects of cardio-oncology encountered in patients with breast cancer, rectal cancer, and lung cancer, who are frequently the recipients of multiple cardiotoxic treatments. Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah. Access the CardioNerds Cardiac Amyloidosis Series for a deep dive into this important topic. This episode is supported by a grant from Pfizer Inc. This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero Abreu, Dr. Dinu Balanescu, and Dr. Teodora Donisan.  Pearls • Notes • References • Production Team CardioNerds Cardio-Oncology PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Cancer Therapy-Related Cardiac Dysfunction (CTRCD) – The Oncologist Perspective with Dr. Susan Dent Formal cardiovascular risk stratification must be performed prior to initiating a potentially cardiotoxic anticancer treatment regimen. Considering both drug toxicity and patient-related factors (e.g., age, smoking, hypertension etc) is important.  Anthracyclines affect the cardiomyocyte in complex ways which lead to a largely irreversible cardiomyopathy. All patients should have a pretreatment echocardiogram and ECG.  Trastuzumab cardiotoxicity, by contrast, is more like stunning the myocardium, which manifests as a reversible decrease in left ventricular ejection fraction which generally normalizes upon discontinuation of the drug.  The treatment of chemotherapy-induced cardiomyopathy should involve interdisciplinary discussions and shared decision making with the patient. Beyond guideline-directed medical therapy of heart failure with reduced ejection fraction, management can include temporarily holding or permanently discontinuing the offending agent.  Fluoropyrimidine-associated cardiotoxicity manifests as cardiac ischemia from coronary vasospasm. A 5FU infusion is essentially a stress test as it tends to unmask clinically silent atherosclerosis.  Show notes What is the basic pretreatment assessment of any oncology patient who is to receive a potentially cardiotoxic regimen?  Awareness and management of the cardiovascular toxicity of oncology treatments are of paramount importance to be able to deliver treatment safely and to achieve maximal efficacy guided by an expert multidisciplinary team. Thanks to Dr. Dent and her colleagues' work, this year we have seen the publication of the first Cardio-Oncology guideline (1). Perhaps the most important recommendation is that cancer patients about to start a cardiotoxic regimen should undergo formal cardiovascular risk stratification by considering both the adverse profile of the planned treatment...

In this episode of Meeting Mic, we bring you the highlights and insights from the ACR Convergence 2022, as well as Healio's top headlines from the meeting. Virginia G. Kaklamani, MD, DSc, professor of medicine in the division of hematology/oncology at UT Health San Antonio and leader of the breast cancer program at UT Health San Antonio MD Anderson Cancer Center, reviews an abstract presentation on the impact of cyclin-dependent kinase 4/6 inhibitor therapy in patients with advanced breast cancer :00 Aditya Bardia, MD, MPH, director of the breast cancer research program at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, discusses a study on trastuzumab-deruxtecan and its response rate in patients with early breast cancer 5:00 Sara A. Hurvitz, MD, FACP, medical oncologist at UCLA Health, Santa Monica Medical Center, associate professor at David Geffen School of Medicine at UCLA, medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit, and director of the breast cancer clinical trials program at UCLA, examines trastuzumab-deruxtecan's effect on patients with breast cancer who were previously treated with trastuzumab and a taxane. 10:00 Read the full coverage here: Longer CDK 4/6 inhibitor therapy enhances elacestrant benefit in metastatic breast cancer Elacestrant extends PFS among certain women with metastatic breast cancer Trastuzumab deruxtecan ‘new gold standard' in second line for breast cancer subset Ribociclib regimen may be superior to chemotherapy in advanced breast cancer Breast cancer specialist receives lecture award Genomic assay may predict ovarian function suppression benefit in breast cancer subset Disclosures: Bardia reports research funding from or consultant/advisory roles with AstraZeneca, Daiichi Sankyo, Eli Lilly, Genentech, Immunomedics/Gilead Sciences, Merck, Novartis, Pfizer, Radius Health and Sanofi. Hurvitz reports honoraria from Daichi Sankyo and research funding to her institution from Ambrx, Amgen, Arvinas, AstraZeneca, Bayer, CytomX Therapeutics, Daiichi Sankyo, Dantari, Dignitana, Eli Lilly, G1 Therapeutics, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, Immunomedics, MacroGenics, Novartis, OBI Pharma, Orinoco Pharmaceuticals, Pfizer, Phoenix Molecular Designs, Pieris Pharmaceuticals, Puma Biotechnology, Radius Health, Samumed, Sanofi, Seagen and Zymeworks. She also reports her spouse is a shareholder/stockholder in Ideal Implant. Kaklamani reports honoraria from, consultant/advisory roles with, speakers bureau roles with or other relationships with AstraZeneca, Daiichi Sankyo, Genentech, Genomic Health, Gilead Sciences, Novartis, Pfizer and Puma Biotechnology. Please see the abstract for all other researchers' relevant financial disclosures.

Listen to a soundcast of the 8/5/2022 FDA approvals of Enhertu (fam-trastuzumab deruxtecan-nxki) for patients unresectable or metastatic HER2-low breast cancer, and Nubeqa (darolutamide) for adult patients with metastatic hormone-sensitive prostate cancer.”

Dr Modi discusses the significance of the FDA approval of trastuzumab deruxtecan in metastatic HER2-low breast cancer, pivotal efficacy and safety data from the DESTINY-Breast04 trial, and how these findings pave the way for further progress across cancer therapy.

Dr Levy discusses the significance of the FDA approval of trastuzumab deruxtecan in HER2-mutant NSCLC, the pivotal efficacy and safety data from the DESTINY-Lung02 trial, and the optimal use of companion diagnostic tests in the field.

Featuring a slide presentation and related discussion from Dr Joshua Sabari, including the following topics: Recent updates from ASCO 2022 in the use of EGFR- and MET-targeted therapies (0:00) Targeting HER3 in patients with advanced non-small cell lung cancer (NSCLC) with and without EGFR mutations (16:04) Recent updates in therapy for patients with EGFR exon 20 insertion mutations (21:47) DESTINY-Lung04 trial: Trastuzumab deruxtecan for patients with HER2 exon 19 or 20 mutations (2921) Using mutational status in predicting patient benefit from chemoimmunotherapy (34:51) Immune checkpoint inhibition for patients with NSCLC with EGFR mutations (38:41) Combining novel agents with immune checkpoint inhibitors for patients with NSCLC and high PD-L1 expression (47:36) CME information and select publications

On the heels of accelerated approval by the US FDA, Dr. Stephen Liu discusses trastuzumab-deruxtecan (T-DXd) with medical oncologists and clinical investigators, Dr. Lyudmila Bazhenova, from the University of California, San Diego, and Dr. Julian Mazieres, from Toulouse University Hospital. T-DXd is an antibody-drug conjugate now approved for the treatment of HER2-mutant NSCLC, and in this episode, its design, efficacy, and safety are reviewed.

En septiembre de 2002 relataba en un artículo el modo en que un anticuerpo monoclonal impedía el funcionamiento de una molécula que estimulaba el crecimiento del cáncer de mama. El anticuerpo se denominaba entonces Herceptin y, por diversos avatares, ha pasado a llamarse hoy Trastuzumab. Este anticuerpo monoclonal forma parte hoy del arsenal de armas terapéuticas que pueden ser utilizadas para frenar o incluso erradicar el cáncer de mama. En el mismo artículo hablaba de la generación de otro anticuerpo monoclonal que podía unir sus fuerzas con Herceptin para inhibir con mayor eficacia el crecimiento tumoral ¿Qué ha sido de esa nueva esperanza que nacía en aquellos años? ¿Se han hecho realidad? Hoy Trastuzumb, Pertuzumab y fármacos anticancerosos se utilizan en combinación para tratar el cáncer de mama.

En septiembre de 2002 relataba en un artículo el modo en que un anticuerpo monoclonal impedía el funcionamiento de una molécula que estimulaba el crecimiento del cáncer de mama. El anticuerpo se denominaba entonces Herceptin y, por diversos avatares, ha pasado a llamarse hoy Trastuzumab. Este anticuerpo monoclonal forma parte hoy del arsenal de armas terapéuticas que pueden ser utilizadas para frenar o incluso erradicar el cáncer de mama. En el mismo artículo hablaba de la generación de otro anticuerpo monoclonal que podía unir sus fuerzas con Herceptin para inhibir con mayor eficacia el crecimiento tumoral ¿Qué ha sido de esa nueva esperanza que nacía en aquellos años? ¿Se han hecho realidad? Hoy Trastuzumb, Pertuzumab y fármacos anticancerosos se utilizan en combinación para tratar el cáncer de mama.

Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer | NEJM https://www.nejm.org/doi/full/10.1056/NEJMoa2203690#.YsoGdaAS_fY.twitter DESTINY-Changing Results for Advanced Breast Cancer | NEJM https://www.nejm.org/doi/full/10.1056/NEJMe2206661#.YsoGjty1ahE.twitter   Early Detection and Monitoring of Vulnerable Myocardium in Patients Receiving Chemotherapy: Is It Time to Change Tracks? https://www.heartfailure.theclinics.com/article/S1551-7136(11)00037-7/fulltext#.YsoHTLcs3-M.twitter Using a Magnet to Strike Gold https://www.heartfailure.theclinics.com/article/S1551-7136(09)00026-9/fulltext#.YsoG3Cq5rAs.twitter

Featuring an interview with Dr Adam Brufsky, including the following topics: Trastuzumab deruxtecan (T-DXd) for HER2-low breast cancer; recently presented findings from the DESTINY-BREAST04 trial (0:00) Impact of heterogeneous disease on the detection of HER2-low expression in patients with breast cancer (7:48) Case: A woman with low-volume, asymptomatic and nonvisceral ER-positive, HER2-low breast cancer (13:16) Case: A woman with high-volume, symptomatic and visceral HER2-low breast cancer; treating ER-negative, HER2-low disease (18:44) Toxicities associated with T-DXd (25:25) Ongoing trials evaluating T-DXd in earlier lines of therapy (31:28) CME information and select publications

Dr. Rachna Shroff, of the University of Arizona Cancer Center, tells guest host, Dr. Shaalan Beg, of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Science 37, about advances in precision medicine for pancreatic cancer featured at the 2022 ASCO Annual Meeting. She also highlights compelling new data from the FOLFOX, FOENIX-CCA2, and HERB trials in hepatocellular carcinoma, cholangiocarcinoma, and biliary tract cancer.   TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Shaalan Beg, your guest host of the ASCO Daily News podcast today. I'm an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. I'm delighted to welcome Dr. Rachna Shroff, the associate dean for clinical and translational research and the chief of gastrointestinal (GI) medical oncology at the University of Arizona Cancer Center where she's also the interim chief of Hematology-Oncology. Dr. Shroff is also the chair-elect for the Gastrointestinal Cancer Symposium. Today we'll be discussing key abstracts in GI cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all our guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Shroff, thank you for being on the podcast today. Dr. Rachna Shroff: Thank you so much for having me. Dr. Shaalan Beg: Let's begin by reviewing what is new in the realm of precision medicine in GI cancers. One of the diseases where precision medicine has not made adequate inroads is pancreatic cancer. One of the most common mutations in pancreas cancer is KRAS, but there haven't been a lot of treatments that can target the most common forms of KRAS. What did we hear at ASCO22 regarding precision medicine and pancreatic cancer? Dr. Rachna Shroff: I agree, I think that the area of precision oncology is, unfortunately, lagging behind a little bit in pancreatic cancer. But I think as we have gotten better and better with our comprehensive genomic profiling, we are identifying subsets of patients within pancreas cancer who are potentially amenable to targeted therapies. You already mentioned KRAS mutations, and we obviously have a number of inhibitors in development in that space, though, we are still missing that key G12D mutation that we see in pancreas cancer. But what I think was really interesting that came out of ASCO22, was a lot of interest and emphasis on better understanding the KRAS wild-type patients in pancreatic cancer. Now, this is obviously a smaller subset of patients, given that the majority of patients have KRAS mutations. But there was a really interesting abstract, LBA4011, that looked at patients with locally advanced or metastatic pancreatic cancer, who were KRAS wild-type. They actually received gemcitabine in combination with a monoclonal antibody targeting EGFR and nimotuzumab. This was a study that was done entirely in Asia. It involved 92 Chinese patients that were randomly assigned to receive the combination of nimotuzumab with gemcitabine. What was interesting in this study is that the patients were found in the full analysis set to have a significantly longer median overall survival of 10.9 months versus 8.5 months with a hazard ratio of 0.5. So, that of course was intriguing and provocative for sure. Similarly, the other endpoints were also somewhat intriguing in terms of improvements in the median progression-free survival (PFS), etc. And specifically, patients without biliary obstruction had a longer PFS, which was an interesting finding as well. The nimotuzumab overall was pretty well tolerated and not any sort of surprising treatment-related adverse events (TRAEs) were noted. And so, this is definitely a drug that, I think, piques our interest in terms of being able to target patients with KRAS wild-type pancreatic cancer. I think that questions, however, that remain, and I think require further study is really understanding what this drug could do in combination with the chemotherapy combinations that we use more frequently in metastatic pancreatic cancers such as gemcitabine and paclitaxel or 5FU-based regimens like FOLFIRINOX. I think given that it is a relatively well-tolerated drug, it would be a very reasonable thing to investigate this drug further in the KRAS wild-type population with the kind of modern-day chemotherapy regimens that we use. And I think, of course, we all know that it is useful to be able to look at these types of drugs in a more global population. And so, a larger patient set I think would be very useful as well, but at least it tells us that there is a way to think about our KRAS wild-type patients with pancreas cancer and that perhaps we really need to understand and identify those patients' potential for precision oncology. Dr. Shaalan Beg: One of the GI cancers that has been a hotbed for precision medicine is cholangiocarcinoma, a disease that's very close to your heart. What updates did we hear at ASCO22 regarding cholangiocarcinoma and precision medicine? Dr. Rachna Shroff: This space of targeted therapy and cholangiocarcinoma has been incredibly exciting for the last few years and I think drug development has been rapid-fire in that space. The oldest, if you will, target that we've been thinking about for some time is the FGFR2 fusion patient population. And in Abstract 4009 by Dr. Goyal and colleagues, we saw the results of the FOENIX-CCA 2 trial which was looking at an oral FGFR inhibitor (futibatinib) in patients with intrahepatic cholangiocarcinoma, who harbor FGFR2 fusions and gene rearrangements. We had initially seen some of this data presented a few years back, but this was the updated data set. It was a single-arm phase 2 study that involved patients with advanced intrahepatic cholangiocarcinoma who had identified FGFR2 gene fusions, and they received futibatinib daily until progression. This was a traditional single-arm phase 2 study with a primary endpoint of overall response rate. At the final data cut, with a median follow-up of 25 months, there's actually a confirmed overall response rate of 41.7%. And I think that what was really exciting about this is this is a refractory patient population. So, in patients who have refractory cholangiocarcinoma, the other drugs, the non-targeted therapy drugs that we think through, really have response rates more in the single-digit to 10% range and so to have a confirmed overall response (OR) over 40% is truly exciting. The duration of the response was also exciting. This is not just a drug that works briefly, it has a duration of response of 9.5 months. And the mature median overall survival was 20 months. And in a disease which we talk about with the ABC-02 data of GemCis, a median OS in advanced disease of 11.7 months. This is really, really exciting for patients who harbor this fusion or gene rearrangement. We know that that's seen in about 10 to 15% of patients. So, again, we're dealing with a smaller subset, but it clearly demonstrates the need to identify FGFR2 gene fusions, so that we can offer these types of targeted therapies. This was not the first FGFR inhibitor that we have seen data on and in fact, we have 2 drugs already U.S. Food and Drug Administration (FDA) approved. And so, when we look at the common treatment-related adverse events that were identified with the futibatinib, there are really class effects related to FGFR inhibition like hyperphosphatemia, alopecia, dry mouth, nothing that really stood out or that was concerning. And so, I think this final analysis for the FOENIX study really just reaffirms the utility of futibatinib in patients with FGFR2 gene fusions, and the mature OS data, the duration of response, all of this really aligns with the need to identify patients with this alteration so that we can, post-gemcitabine based therapies, offer this targeted therapy or an FGFR inhibitor in general to these patients. I think the other really exciting abstract in the glandular carcinoma or biliary tract cancer space was Abstract 4006. This was the updated data from the HERB trial, which was an investigator-initiated multicenter phase 2 trial looking at trastuzumab deruxtecan (T-DXd) in patients who have HER2 expressing unresectable or recurrent biliary tract cancer. Trastuzumab deruxtecan, I'm sure everybody has been hearing about because it has been incredibly effective in HER2 alterations across a myriad of different disease sites. And so, not wanting to be left out, biliary tract cancers were investigated in this study with patients who had HER2 expression, so, that was HER2-positive IHC3+ or IHC2+/ISH+, and they also looked at HER2-low expressing patients, and [whose disease] were refractory or intolerant to gemcitabine-based therapy with the primary endpoint of overall response rate. So, in the HERB trial, a total of 32 patients were enrolled. 24 of them were HER2-positive and 8 were HER2-low and they all received trastuzumab deruxtecan. When you look at the efficacy data, the confirmed overall response rate in the patients with HER2-positive was 36.4%, which again, as I said, in a refractory patient population is certainly very exciting data. And the overall disease control median, PFS, and median OS were all pretty encouraging in terms of efficacy. What was also kind of intriguing was that there was some efficacy seen even in the patients who are HER2-low. Now, this is, in my opinion, a slightly less exciting amount of efficacy, but still important to note that the overall response rate in HER2-low was 12.5% with a median PFS that was also somewhat exciting at 4.2 months. And so, there is a potential clearly for targeting patients with HER2-high or HER2-positive with trastuzumab deruxtecan, and I think in the patients who are HER2-low, we need to better understand the potential utility. The common treatment-related adverse events that we see were the typical things that we've heard about with trastuzumab deruxtecan, but I think the one thing that was really worth noting was 8 patients or 25% of patients had interstitial lung disease (ILD), which we know is an important identified safety concern for patients who receive trastuzumab deruxtecan, and I think that's a pretty sizable number of 25%, so, I think that's going to really require a little bit more fleshing out for us to understand the safety for these patients. One question that a lot of us have had is whether these are patients who have received gemcitabine, which we know can also cause pneumonitis. And so, I don't know if we're seeing a higher percentage of ILD because of, 'priming' with prior gemcitabine. But regardless, I think this is just proof of principle that again, we need to identify patients with biliary tract cancers that have HER2-positivity because we now have a number of drugs including potentially trastuzamab deruxtecan to target [their disease] with after gemcitabine-based treatments Dr. Shaalan Beg: Absolutely. Any new biomarkers to keep on the radar for our listeners? Dr. Rachna Shroff: I think there are a lot of really exciting targets. One that was talked about and that we saw data on at ASCO [Annual Meeting] was from Abstract 4048, which looked at claudin [18]. Claudin is basically a transmembrane protein that kind of helps maintain the tight junctions between cells. In gastric cancer, in particular, we look at claudin 18 isoform 2, and there are 18.1 and 18.2 gene expressions that have been identified in gastric cancer. So, there was a very comprehensive abstract that was presented of over 1,900 samples that underwent comprehensive profiling by next-generation sequencing. And the patients were identified with claudin 18.1, and 18.2, high versus low. Claudin 18.2 expression was actually detected in 97% of the samples. It's slightly lower with claudin 18.1 at 63%. It's important to note that the primary tumors had higher expression levels than the metastatic tumors, so those were really the tumors in which they did a deeper dive. And in the process of doing this deeper dive, they did a really interesting kind of better understanding of the immune microenvironment and the immune profile in the samples that had claudin expression. And what was identified is that there was an inverse relationship basically between claudin 18.1 and 18.2 expression and correlation with PD-L1 positivity, tumor mutational burden (TMB)-high, M1 macrophages expression, NK cell presence, CD4 positive T-cells, myeloid dendritic cells. And so, there's clearly something between the presence of this claudin expression and the effect it has on the immune microenvironment. I think that's very relevant to keep in mind because as we all know, there's a whole space of drug development focused right now on anti-claudin 18.2 monoclonal antibodies, as well as a target for antibody-drug conjugates (ADC) and cellular therapies with CAR T-cell therapies being developed specifically against claudin 18. And so, understanding the immune microenvironment and the interaction between the claudin expression will be really important as we continue to charge forward in that space. Dr. Shaalan Beg: Absolutely. Very, very exciting. Sticking with the liver pancreas theme, what other studies piqued your interest with regards to hepatocellular carcinoma (HCC)? Dr. Rachna Shroff: It's a really exciting time in HCC. I mean, we actually have drugs that are working in the advanced space. And so, now there's a lot of interest in shifting to looking at preoperative neoadjuvant, and adjuvant approaches and what we can do to improve disease-free survival and overall survival in patients who are able to undergo prior resection. So, Abstract 4013 looked specifically at the efficacy and safety of adjuvant hepatic arterial infusion chemotherapy with FOLFOX. And this was a randomized open-label phase 3 trial. It actually included a total of 315 patients between 5 different centers and patients were randomly assigned to receive either 1 to 2 cycles of adjuvant HAIC FOLFOX (Hepatic Arterial Infusion Chemotherapy FOLFOX) versus just follow up, the control group had no adjuvant treatment, and the primary endpoint was disease-free survival here and in the intention to treat population, there was a significantly improved median disease-free survival at 27 months versus 11 months in the patients who were on the control arm. And there was a protocol analysis, there were a number of other efficacy endpoints including disease-free survival rates at 1, 2, and 3 years. And everything kind of leaned towards and or suggested an improvement with the utility of HAI FOLFOX in patients who undergo complete resection. It should be noted that this included patients specifically who had microvascular invasion on their resection. And so, these are patients who are at higher risk for recurrence as we know. This to me suggests that there could be a role for adjuvant treatment in patients who undergo complete resection with microvascular invasion (MVI). HAI is a very specific technique and it requires a highly skilled center in the placement of HAI pumps. And we're seeing more and more trials across the U.S. as well investigating the role of HAI in advanced disease and in perioperative approaches. And so, I think this is an area of much-needed continued research. There are, of course, a number of ongoing adjuvant studies looking at immunotherapy in the adjuvant setting. And so, it'll be really important to see how those read out and then to try to put all of these in context so that we can better understand local therapy like HAI FOLFOX versus more systemic adjuvant approaches like immunotherapy. Dr. Shaalan Beg: Thank you very much, Dr. Shroff for sharing your valuable insights with us. I really appreciate you taking the time to spend with us and our listeners. Dr. Rachna Shroff: Thanks so much. I enjoyed it. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, we'd really like to hear your feedback. If you could please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much!   Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics Disclaimer: The purpose of this podcast is to educate and 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.  

On May 4, the FDA approved fam-trastuzumab deruxtecan-nxki for pretreated adult patients with unresectable or metastatic HER2-positive breast cancer. We highlight findings from the DESTINY-Breast03 trial that led to the regular approval, and also hear from Dr. Sara Hurvitz, of the University of California, Los Angeles Jonsson Comprehensive Cancer Center, who discussed the trial results with The ASCO Post at the 2021 San Antonio Breast Cancer Symposium.Coverage of stories discussed this week on ascopost.com:FDA Grants Regular Approval to Fam-Trastuzumab Deruxtecan-nxki for Unresectable or Metastatic HER2-Positive Breast CancerTo listen to more podcasts from ASCO, visit asco.org/podcasts.

Trastuzumab deruxtecan vs. trastuzumab trastuzumab