Podcasts about her2

We love to hear from our listeners. Send us a message. On this week's episode of the Business of Biotech, Brian Hilberdink, President of U.S. Human Pharma at Boehringer Ingelheim, returns to the show during the J.P. Morgan Healthcare Conference, and following his departure from LEO Pharma (see episode 164). Brian talks about new opportunities in obesity, the benefits of private ownership in funding early science, Boehringer's deal strategy, using AI to improve commercialization efforts, and the FDA's selection of zongertinib (in patients with HER2-mutant NSCLC) for the Commissioner's National Priority Voucher program.    Access this and hundreds of episodes of the Business of Biotech videocast under the Business of Biotech tab at lifescienceleader.com. Subscribe to our monthly Business of Biotech newsletter. Get in touch with guest and topic suggestions: ben.comer@lifescienceleader.comFind Ben Comer on LinkedIn: https://www.linkedin.com/in/bencomer/

Is the era of cisplatin over, or are we simply becoming more precise about who benefits from it? As perioperative strategies in bladder cancer continue to evolve, emerging tools like circulating tumor DNA (ctDNA) are playing a bigger role in how clinicians assess recurrence risk and tailor treatment. In this episode of BackTable Tumor Board, host Alan Tan, medical oncologist at Vanderbilt-Ingram Cancer Center, is joined by bladder cancer experts Dr. Amanda Nizam and Dr. Brad McGregor to discuss recent advances in the diagnosis and treatment of urothelial carcinoma. --- SYNPOSIS The doctors examine the evolving management of muscle-invasive bladder cancer (MIBC), including the role of neoadjuvant and adjuvant therapies, the integration of immunotherapy, and the recent approval of enfortumab vedotin plus pembrolizumab. The discussion explores the rapidly changing perioperative landscape, the prognostic utility of ctDNA, and how biomarkers such as HER2 and FGFR are influencing treatment selection across disease states. They also address bladder preservation strategies, management of treatment-related toxicities, and the importance of multidisciplinary coordination. The episode concludes with a forward-looking discussion on emerging therapies and the potential to improve cure rates in bladder cancer. --- TIMESTAMPS 00:00 - Introduction01:44 - Overview of Bladder Cancer Treatment04:54 - Patient Staging and Treatment Goals10:12 - Bladder Preservation vs. Radical Cystectomy16:39 - Emerging Trials and Future Directions22:40 - ctDNA and Precision Medicine33:50 - Metastatic Disease and Biomarker Strategies42:16 - Managing Neuropathy in Metastatic Treatment48:44 - HER2 and FGFR in Bladder Cancer54:15 - Future Directions in Bladder Cancer Treatment --- RESOURCES EV-302/303 Trialhttps://newsroom.astellas.com/2023-12-15-PADCEV-R-enfortumab-vedotin-ejfv-with-KEYTRUDA-R-pembrolizumab-Approved-by-FDA-as-the-First-and-Only-ADC-Plus-PD-1-to-Treat-Advanced-Bladder-Cancer NIAGARA Regimenhttps://www.nejm.org/doi/full/10.1056/NEJMoa2408154 KEYNOTE-905 Studyhttps://www.annalsofoncology.org/article/S0923-7534(25)04894-X/fulltext

In today's episode, the discussion features Aditya Bardia, MD, MPH, FASCO. Dr Bardia is a professor in the Department of Medicine in the Division of Hematology/Oncology, the director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at the UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, California.In the exclusive interview, Dr Bardia discussed the rationale and design of the phase 3 ELEGANT study (NCT06492616), which is evaluating elacestrant (Orserdu) compared with standard endocrine therapy in patients with estrogen receptor–positive, HER2-negative early breast cancer at high risk of disease recurrence.

Did you know that as MBC patients get treated with multiple lines of ET, the percentage of patients who develop an ESR1 mutation increases? Credit available for this activity expires: 1/26/27 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/current-and-future-oral-serd-strategies-management-er-2026a100022b?ecd=bdc_podcast_libsyn_mscpedu

Featuring perspectives from Dr Haley Ellis, Prof Eric Van Cutsem and Dr Zev Wainberg, moderated by Dr Lionel A Kankeu Fonkoua, including the following topics:  Introduction (0:00) Biliary Tract Cancers — Dr Ellis (1:56) Gastroesophageal Cancers — Dr Wainberg (24:27) Colorectal Cancer — Prof Van Cutsem (59:13) CME information and select publications

Dr Haley Ellis from Harvard Medical School in Boston, Massachusetts, Prof Eric Van Cutsem from University Hospitals Leuven in Belgium, Dr Zev Wainberg from UCLA School of Medicine in Los Angeles, California, and moderator Dr Lionel KankeuFonkoua from Mayo Clinic in Rochester, Minnesota, discuss recent data surrounding the management of HER2-positive GI cancers, alongside their perspectives on its clinical application and management.CME information and select publications here.

Dr Haley Ellis from Harvard Medical School in Boston, Massachusetts, Prof Eric Van Cutsem from University Hospitals Leuven in Belgium, Dr Zev Wainberg from UCLA School of Medicine in Los Angeles, California, and moderator Dr Lionel KankeuFonkoua from Mayo Clinic in Rochester, Minnesota, discuss recent data surrounding the management of HER2-positive GI cancers, alongside their perspectives on its clinical application and management.CME information and select publications here.

Featuring perspectives from Dr Angela DeMichele, Dr Komal Jhaveri, Dr Erica Mayer, Dr Hope S Rugo and Dr Seth Wander, including the following topics:  Introduction (0:00) 1985 NCI Consensus Conference on Early Breast Cancer: Sir Richard Peto, FRS (2:01) Current Role of Genomic Assays in Treatment Decision-Making for Localized Hormone Receptor (HR)-Positive Breast Cancer — Dr DeMichele (5:13) Case: A premenopausal woman in her mid 40s with an ER-positive, HER2-negative, node-negative infiltrating ductal carcinoma (IDC) after partial mastectomy/radiation therapy who enrolls in the prospective, observational FLEX study: MammaPrint® low risk — Laurie Matt-Amaral, MD, MPH (15:30) Case: A premenopausal woman in her mid 40s after modified radical mastectomy for T2N0 ER-positive, HER2-negative IDC with an Oncotype DX® Recurrence Score (RS®) of 19 — Swati Vishwanathan, MD Case: A woman in her mid 60s with locally advanced (19 cm) ER-positive, HER2-low (IHC 1+) Stage IIIB mucinous carcinoma breast cancer and an RS of 18 — Alan B Astrow, MD (22:40) Role of CDK4/6 Inhibitors and Other Novel Strategies in Therapy for HR-Positive, HER2-Negative Localized Breast Cancer — Dr Jhaveri (30:18) Case: A woman in her mid 50s with ER-positive, HER2-negative Stage IIB, T2N1 IDC after neoadjuvant dose-dense AC-T, lumpectomy and adjuvant radiation therapy — Eleonora Teplinsky, MD (42:14) Case: A woman in her mid 60s with ER-positive, HER2-negative breast cancer with a surgically removed solitary lung metastasis after 4 years of adjuvant letrozole — Eric Fox, DO (46:32) Evolving Up-Front Treatment Paradigm for HR-Positive, HER2-Negative Metastatic Breast Cancer (mBC) — Dr Rugo (49:45) Case: A woman in her early 80s with Type 2 diabetes, well controlled hypertension and recurrent ER-positive, HER2-negative mBC after 4 years of adjuvant letrozole — Sunil Gandhi, MD (1:02:30) Clinical Utility of Agents Targeting the PI3K/AKT/mTOR Pathway for Patients with Progressive HR-Positive mBC — Dr Mayer (1:06:37) Case: A woman in her late 60s with ER-positive, HER2-low (IHC 1+), PIK3CA-mutant mBC with disease progression after 2 years of adjuvant letrozole — Laila Agrawal, MD (1:20:22) Case: A woman in her early 60s with ER-positive, HER2-low PIK3CA-mutant mBC and disease progression on first-line palbociclib/fulvestrant — Dr Teplinsky (1:26:36) Results from the Global Phase III lidERA Breast Cancer Trial of Giredestrant versus Standard Endocrine Therapy as Adjuvant Treatment for ER-Positive, HER2-Negative Localized Breast Cancer (1:31:48) Current and Future Role of Oral Selective Estrogen Receptor Degraders for Progressive HR-Positive mBC — Dr Wander (1:42:30) Case: A woman in her early 100s with locally advanced ER-positive, HER2-negative breast cancer with disease progression on letrozole, now with an ESR1 mutation — Dr Astrow (1:57:51) CME information and select publications

In this podcast, experts William J. Gradishar, MD, FASCO, FACP; Stephanie L. Graff, MD, FACP, FASCO; and Cynthia X. Ma, MD, PhD; discuss current and emerging therapeutic options, including next-generation endocrine therapies, to target the estrogen receptor signaling pathway for the treatment of hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (MBC).

Marybeth was diagnosed with stage 0 ER+, HER2+ breast cancer in 2007 at age 39, and 13 years later learned her cancer had metastasized to her bones and lymph system. At her therapist's suggestion, she read Radical Remission, which gave her hope, shifted her mindset, and showed her that healing beyond the statistics was possible. The book propelled her to explore peer-reviewed research and adopt powerful anti-cancer strategies. Within three months she achieved a complete pathological response, and she has now been cancer-free for more than five years. Outperform Cancer Website: www.outperformcancer.com Outperform Cancer Podcast on Apple and Spotify Facebook: https://www.facebook.com/outperformcancer Instagram: https://www.instagram.com/marybethgilliam Threads: https://www.threads.com/@marybethgilliam X: https://x.com/marybethgilliam Blue Sky: https://bsky.app/profile/outperformcancer.bsky.social Resources: American Association for Cancer Research (AACR)-https://www.aacr.org/ National Breast Cancer Coalition (NBCC)-https://www.stopbreastcancer.org/ ___________ To learn more about the 10 Radical Remission Healing Factors, connect with a certified RR coach or join a virtual or in-person workshop visit www.radicalremission.com.   To watch Episode 1 of the Radical Remission Docuseries for free, visit our YouTube channel here.  To purchase the full 10-episode Radical Remission Docuseries visit Hay House Online Learning. To learn more about Radical Remission health coaching with Liz or Karla, Click Here Follow us on Social Media: Facebook  Instagram YouTube _______________

In this podcast, experts Erika P. Hamilton, MD; Giuseppe Curigliano, MD, PhD; VK Gadi, MD, PhD; Jason Aboudi Mouabbi, MD, discuss frontline, second-line, and antibody-drug conjugate therapies for the treatment of HR-positive, HER2-negative metastatic breast cancer.

In this podcast, experts Tiffany A. Traina, MD, FASCO, Kevin Kalinsky, MD, MS, FASCO, Mark E. Robson, MD, FASCO, and Rebecca Shatsky, MD discuss data for CDK4-6 inhibitors, PARP inhibitors, and immune checkpoint inhibitors in the management of early-stage hormone receptor-positive, HER-2-negative breast cancer.

In this podcast, experts Sara A. Hurvitz, MD, FACP, Michelle Melisko, MD, and Paolo Tarantino, MD, PhD, discuss approaches to maintenance and subsequent lines of therapy for patients with HER2+ advanced breast cancer, including those with CNS metastases.

We're kicking off 2026 with practice-changing data fresh from GI ASCO 2026. In this episode, we were joined once again by Dr. Rachna Shroff from the University of Arizona Cancer Center to break down the four most pivotal studies in upper GI and colorectal cancers presented at the GI ASCO 2026. We dived into the latest updates that will directly impact your clinical decisions, from new standards in perioperative therapy to revolutionary front-line regimens for metastatic disease. Key topics covered in this episode: ● MATTERHORN update: Surgical outcomes & FLOT modifications with Durvalumab in resectable gastric/GEJ cancer ● HERIZON-GEA-01: Zanidatamab + chemo + Tislelizumab the new frontline standard for HER2+ gastric cancer ● BREAKWATER: Confirming Encorafenib + Cetuximab + chemo (FOLFOX or FOLFIRI) for BRAF V600E mCRC ● COMMIT: Chemo + Atezolizumab vs. Atezolizumab alone in MSI-H/dMMR metastatic colorectal cancer Tune in for this dense, insightful recap and stay ahead of the curve. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for more expert analysis on treatment algorithms and major conference highlights! #OncologyBrothers #GI26 #GastricCancer #ColorectalCancer #HER2 #BRAF #MSI #OncologyPodcast

Featuring perspectives from Prof Giuseppe Curigliano, Prof Nadia Harbeck, Dr Ian E Krop, Dr Nancy U Lin and Dr Joyce O'Shaughnessy, including the following topics:  Introduction (0:00) Considerations in the Care of Patients with Localized HER2-Positive Breast Cancer — Prof Harbeck (1:39) Case: A woman in her mid 50s presents with locally advanced ER-positive, HER2-positive breast cancer — Alan B Astrow, MD (12:52) Case: A woman in her mid 40s with ER-positive, HER2-positive Stage II breast cancer s/p neoadjuvant TCHP with residual disease receives adjuvant T-DM1 but discontinues due to neuropathy — Laila Agrawal, MD (20:02) Previously Untreated HER2-Positive Metastatic Breast Cancer (mBC) — Prof Curigliano (25:10) Case: A woman in her early 80s presents with de novo metastatic (bone-only) ER-positive, HER2-positive breast cancer — Zanetta S Lamar, MD (35:03) Optimal Management of Brain Metastases in Patients with HER2-Positive Breast Cancer — Dr Lin (46:20) Case: A woman in her early 60s with ER-positive, HER2-positive breast cancer develops a cerebellar metastasis while receiving adjuvant anastrozole after prior anti-HER2 therapy — Justin Favaro, MD, PhD (59:41) Case: A woman in her early 40s with ER-negative, HER2-positive mBC develops a headache shortly after neoadjuvant TCHP, surgery and postneoadjuvant T-DM1 and is found to have an isolated 4-cm brain metastasis — Dr Agrawal (1:05:36) Selection and Sequencing of Therapy for Relapsed/Refractory HER2-Positive mBC in the Absence of CNS Involvement — Dr Krop (1:12:00) Case: A woman in her early 40s with ER-positive, HER2-positive mBC receives THP (docetaxel/trastuzumab/pertuzumab) and maintenance tucatinib with trastuzumab/pertuzumab on a clinical trial and now has disease progression — Yanjun Ma, MD, PhD (1:23:04) Tolerability Considerations with HER2-Targeted Therapies — Dr O'Shaughnessy (1:29:32) Case: A woman in her mid 60s presents with localized ER-negative, HER2-positive infiltrating ductal carcinoma — Erik Rupard, MD (1:46:06) Case: A woman in her early 70s with recurrent ER-positive, HER2-positive mBC receives trastuzumab deruxtecan (T-DXd) and has concerning pulmonary symptoms but without findings on diagnostic imaging — Kimberly Ku, MD Case: A woman in her mid 40s with ER-positive, HER2-positive breast cancer metastatic to the brain and lung who received multiple prior treatments responds to T-DXd but develops Grade 1 interstitial lung disease — Richard Zelkowitz, MD (1:49:49) CME information and select publications

Prof Giuseppe Curigliano from the University of Milan in Italy, Prof Nadia Harbeck from LMU University Hospital in Munich, Germany, Dr Ian E Krop from Yale Cancer Center, Dr Nancy U Lin from Dana-Farber Cancer Institute and Dr Joyce O'Shaughnessy from Baylor University Medical Center discuss real-world cases and recent clinical data pertinent to the management of HER2-positive breast cancer. CME information and select publications here.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/NXT865. CME/MOC/NCPD/AAPA/IPCE credit will be available until January 15, 2027.Dialing Up Precision in HR+, HER2- MBC With New Endocrine Agents, Targeted Therapies, and Combinations: A Framework for Multifactorial Clinical Decisions In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Genentech, a member of the Roche Group, Lilly, and Stemline Therapeutics, a Menarini Company Group.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/EBAC information, and to apply for credit, please visit us at PeerView.com/THG865. CME/EBAC credit will be available until January 10, 2027.Precision Tactics With HER2-Targeting ADCs in HER2-Altered Solid Tumors: Candid Conversations and Clinical Consults In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.

Dr. Hope Rugo and Dr. Vivek Subbiah discuss innovative trial designs to enable robust studies for smaller patient populations, as well as the promise of precision medicine, novel therapeutic approaches, and global partnerships to advance rare cancer research and improve patient outcomes. TRANSCRIPT  Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center [in Los Angeles]. The field of rare cancer research is rapidly transforming thanks to progress in clinical trials and treatment strategies, as well as improvements in precision medicine and next-generation sequencing that enable biomarker identification. According to the National Cancer Institute, rare cancers occur in fewer than 150 cases per million each year, but collectively, they represent a significant portion of all cancer diagnoses. And we struggle with the appropriate treatment for these rare cancers in clinical practice. Today, I am delighted to be joined by Dr. Vivek Subbiah, a medical oncologist and the chief of early-phase drug development at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Subbiah is the lead author of a paper in the ASCO Educational Book titled "Designing Clinical Trials for Patients with Rare Cancers: Connecting the Zebras," a great title for this topic. He will be telling us about innovative trial designs to enable robust studies for small patient populations, the promise of precision medicine, and novel therapeutic approaches to improve outcomes, and how we can leverage AI now to enroll more patients with rare cancers in clinical trials. Our full disclosures are available in the transcript of this episode.  Dr. Subbiah, it is great to have you on the podcast today. Thanks so much for being here. Dr. Vivek Subbiah: Thank you so much, Dr. Rugo, and it is an honor and pleasure being here. And thank you for doing this podcast for rare cancers. Dr. Hope Rugo: Absolutely. We are excited to talk to you. And congratulations on this fantastic paper. It is such a great resource for our community to better understand what is new in the field of rare cancer research. Of course, rare cancers are complex and multifaceted diseases. And this is a huge challenge for clinical oncologists. You know, our clinics, of course, cannot be designed as we are being very uni-cancer focused to just be for one cancer that is very rare. So, oncologists have to be a jack of all trades in this area. Your paper notes that there are approximately 200 distinct types of rare and ultra-rare cancers. And, by definition, all pediatric cancers are rare cancers. Of course, clinical trials are essential for developing new treatment strategies and improving patient outcomes, and in your paper, you highlight some unique challenges in conducting trials in this rare cancer space. Can you tell us about the challenges and how really innovative trial designs, I think a key issue, are being tailored to the specific needs of patients with rare cancer and, importantly, for these trials? Dr. Vivek Subbiah: Rare cancers present a perfect storm of challenges. First, the patient populations are very small, which makes it really hard to recruit enough participants for traditional type trials. Second, these patients are often geographically dispersed across multiple cities, across multiple states, across multiple countries, across multiple zip codes. So, logistics become complicated. Third, there is often limited awareness among clinicians, which delays referrals and diagnosis. Add to that regulatory hurdles, funding constraints, and you can see why rare cancer trials are so tough to execute. To overcome these barriers, we are seeing some really creative novel trial designs. And there are four different types of trial designs that are helping with enrolling patients with rare cancers. The first one is the basket trial. So let us talk about what basket studies are. Basket studies group patients based on shared genetic biomarkers or shared genetic mutations rather than tumor type. So instead of running separate 20 to 30 to 40 trials, you can study one therapy across multiple cancers. The second type of trial is the umbrella trial. The umbrella trials flip that concept of basket studies. They focus on one cancer type but test multiple targeted therapies within it. The third category of innovative trials are the platform studies. Platform trials are another exciting innovation. They allow new treatment arms to be added or removed as the data matures and as the data evolves, making trials more adaptive and efficient. The final category are decentralized tools in traditional trials, which are helping patients participate closer to where they are so that they can sleep in their own bed, which is, I think, a game changer for accessibility.  These designs maximize efficiency and feasibility for rare cancer research and rare cancer clinical trials. Dr. Hope Rugo: I love the idea of the platform trials that are decentralized. And I know that there is a trial being worked on with ARPA-H (Advanced Research Projects Agency for Health) funding in triple-negative breast cancer as well as in lung cancer, I think, and others with this idea of a platform trial. But it is challenged, I think, by precision medicine and next-generation sequencing where some patients do not have targetable markers, or there isn't a drug to target the marker. I think those are almost the same thing. We have really seen that these precision medicine ideas and NGS have moved the needle in helping to identify genetic alterations. This helps us to be more personalized. It actually helps with platform studies to customize trial enrollment. And we hope that this will result in better outcomes. It also allows us, I think, to study drugs even in the early stage setting more effectively. How can these advances be best applied to the future of rare cancers, as well as the challenges of not finding a marker or not having a drug? Dr. Vivek Subbiah: Thank you so much for that question. I think precision medicine and next-gen sequencing, or NGS, are truly the backbone of modern precision oncology. They have transformed how we think about cancer treatment. Instead of treating based on where the tumor originated or where the tumor started, we now look at the genetic blueprint of cancer. The NGS or next-gen sequencing allows us to sequence millions of DNA fragments quickly. Twenty, 30 years ago, they said we cannot sequence a human genome. Then it took almost a decade to sequence the first human genome. Right now, we have academic centers and commercial sequencing companies that are really democratizing NGS across all sites, not just in academic centers, across all the community sites, so that NGS is now accessible. This means that we can identify these actionable alterations like picking needles in haystacks, like NTRK fusions, RET fusions, or BRAF V600E alterations, high tumor mutational burden. This might occur across not one tumor type, across several different tumor types. So for rare cancers, this is critical because some of these mutations often define the best treatment option. Here is why this matters. Personalized therapy, right? Instead of a one-size-fits-all approach, we can tailor treatment to the patient's unique molecular profile. For trial enrollment, this can definitely help because patients can join biomarker-driven trials even if their cancer type is rare or ultra-rare. NGS technology has also helped us in designing rational studies. Many times monotherapy does not work in these cancers. So we are thinking about rational combination strategies. So NGS technology is helping us. Looking ahead, I see NGS becoming routine in clinical practice, not just at major niche academic centers, but everywhere. We will see more tumor-agnostic approvals, more molecular tumor boards guiding treatment decisions in real time. And I think we are seeing an expanded biomarker setup. Previously, we used to have only a few drugs and a handful of mutations. Now with homologous recombination defects, BRCA1/2 mutation, and expanding the HRD and also immunohistochemistry, we are expanding the biomarker portfolio. So again, I personally believe that the future is precision. What I mean by precision is delivering the right drug to the right patient at the right time. And for rare cancers, this isn't just progress. It is survival. And it is maybe the only way that they can have access to these cutting-edge precision medicines. Dr. Hope Rugo: That is so important. You mentioned an important area we will get to in a moment, the tumor-agnostic therapies. But as part of talking about that, do you think that the trials should also include just standard therapies? You know, who do you give an ADC to and when with these rare cancers? Because some of them do not have biomarkers to target and it is so disappointing for patients and providers where you are trying to screen a patient for a trial or a platform trial where you have one arm with this mutation, one arm with that, and they do not qualify because they only have a p53 loss, you know? They just do not have the marker that helps them. But we see this in breast cancer all the time. And it is tough because we don't have good information on the sequencing. So I wonder, you know, just because for some of these rare cancers it is not even clear what to use when with standard treatments. And then that kind of gets into this idea of the tumor-agnostic therapies that you mentioned. There are a lot of new treatments that are being evaluated. We have seen approval of some treatments in the last few years that are tumor-agnostic and based on a biomarker. Is that the best approach as we go forward for rare cancers? And what new treatment options are most exciting to you right now? Dr. Vivek Subbiah: Tumor-agnostic therapies, really close to my heart, are real breakthrough therapies and represent a major paradigm shift in oncology. Traditionally, for the broad listeners here, we are used to thinking about designing clinical trials and therapy like where the cancer originated, breast cancer, kidney cancer, prostate cancer, lung cancer. A tumor-agnostic therapy flips that model. Instead of focusing on the organ, they target the specific genetic alteration or biomarker that drives cancer growth regardless of where the tumor started, regardless of the location of the tumor, regardless of the zip code of the tumor. So why is this so important for rare cancers? Because many rare cancers share molecular features with more common cancers. For instance, NTRK fusion might occur in pediatric sarcoma, a salivary gland tumor, or a thyroid cancer. Historically, each of these would require separate trials, which is nearly impossible, unfeasible to conduct in these ultra-rare cancers like salivary gland cancer or pediatric sarcomas. Tumor-agnostic therapies allow us to treat all those cancers with the same targeted drug if they share that biomarker. Again, we are in 2025. The first tissue-agnostic approval, the historic precedent, was in fact an immunotherapy. Pembrolizumab was approved in 2017, May 2017, as the first immunotherapy to be approved in a tumor-agnostic way for a genomic biomarker, for MSI-High and dMMR cancers. Then came the NTRK inhibitors. So today we have not one, not two, but three different NTRK inhibitors: larotrectinib, entrectinib, and repotrectinib, which show response rates of nearly more than 60 to 75% across a handful of dozens and dozens of cancer types. Then, of course, we have RET inhibitors like selpercatinib, which is approved tissue-agnostic, and pralsetinib, which also shows tissue-agnostic activity across multiple cancers. And more recently, combination therapy with a BRAF and MEK combination, dabrafenib and trametinib, received tumor-agnostic approval for all BRAF V600E tumors with the exception of colorectal cancer. And even recently, you mentioned about antibody drug conjugates. Again, I think we live in an era of antibody drug conjugates. And Enhertu, trastuzumab deruxtecan, which was used first in breast cancer, now it is approved in a histology-agnostic manner for all HER2-positive tumors defined by immunohistochemistry 3+. So again, beyond NGS, now immunohistochemistry for HER2 is also becoming a biomarker. So again, for the broad listeners here, in addition to comprehensive NGS that may allow patients to find treatment options for these rare cancers for NTRK, RET, and BRAF, immunohistochemistry for HER2 positivity is also emerging as a biomarker given that we have a new FDA approval for this. So I would say personally that these therapies are game changers because they open doors for patients who previously had no options. Instead of waiting for years for a trial in their specific cancer type, they can access a treatment based on their molecular profile. I think it is precision medicine at its finest and best. Looking ahead, the third question you asked me is what is exciting going on? I think we will see more of these approvals. My hope is that today, I think we have nine to ten approvals. My hope is that within the next 25 to 50 years, we will have at least 50 to 100 drugs approved in this space based on a biomarker, not based on a location of the tumor type. Drug targeting rare alterations like FGFR2 fusions, FGFR amplifications, ALK fusions, and even complex signatures like high tumor mutational burden. I think we will be seeing hopefully more and more drugs approved. And as sequencing becomes routine, we will identify more patients for these therapies. I think for rare cancers, this is not just innovative approach. This is essential for them to access these novel precision medicines. Dr. Hope Rugo: Yeah, that is such a good point. I do think it is critical. Interestingly in breast cancer, it hasn't been, you know, there is always like two patients in these tumor-agnostic trials, or if that. You know, I think I have seen one NTRK fusion ever. I think that highlights the importance for rare cancers. And you know, I am hoping that that will translate into some new directions for some of our rarer and impossible-to-treat subtypes of breast cancer. It is this kind of research that is really going to make a difference. But what about those people who do not have biomarkers? What if you do not fit into that? Do you think there is a possibility of trying to do treatments for rare cancers in some prospective way that would help with that? You know, it is really a huge challenge. Dr. Vivek Subbiah: Absolutely. I think, you know, you're right, usually many of these rare cancers are driven by specific biomarkers. And again, some of the pediatric salivary gland tumors or pediatric sarcomas like fibrosarcomas, they are pathognomonic with NTRK fusions. And again, given that we have a tumor-agnostic approval, now these patients have access to these therapies. And I do not think that we would have had a trial just for pediatric fibrosarcomas with NTRK fusions. So that is one way. Another way is SWOG, right? The SWOG DART [1609] had this combination dual checkpoint, it was called the DART study dual combination chemotherapy with ipi/nivo. Now here the rare cancer subtype itself becomes a biomarker and they showed activity across multiple rare cancer subtypes. They didn't require a biomarker. As long as it was a rare or ultra-rare cancer, these patients were enrolled into the SWOG DART trial and multiple arms have read out. Angiosarcoma, Kaposi sarcoma, even gestational trophoblastic disease. Again, they have shown responses in these ultra-rare, rare cancers. Sometimes they might be seeing one or two cases a whole year. And I think this SWOG effort, this cooperative group effort, really highlighted the need for such studies without biomarkers as well. Dr. Hope Rugo: That is such a fantastic example of how to try and treat patients in a collaborative way. And in the paper, you also emphasize the need for collaborative research efforts, you know, uniting resource expertise across different ways of doing research. So cooperative groups, advocacy organizations that can really help advance rare cancer research, improve access to new therapies, and I think importantly influence policy changes. I think this already happened with the agnostic approvals. Could you tell us more about that? How can we move forward with this most effectively? Dr. Vivek Subbiah: Personally, I believe that collaboration is absolutely critical and essential for rare cancer research. No single institution, no single individual, or no single state or entity can tackle these challenges alone. The patient populations are small and dispersed. So pooling resources is the only way to run these meaningful trials. Again, it is not like singing, it is like putting a huge, huge, I would say, an opera piece together. It is not a solo, vocal therapy, but rather putting a huge opera piece like Turandot. You know, you mentioned cooperative groups. Cooperative groups, as I mentioned earlier, the SWOG DART program, the ASCO [TAPUR study]. ASCO is doing a phenomenal work of the TAPUR study. Again, this ASCO TAPUR program has enrolled so many patients with rare cancers who otherwise would not have treatment options. NCI-MATCH, the global effort, right? NCI-MATCH and the ComboMATCH are great examples. They bring together hundreds of sites, thousands of clinicians to run large-scale trials that would be impossible for any individual center or institution. These trials have already changed practice. For instance, the DART demonstrated the power of immunotherapy in rare cancers and influenced NCCN guidelines. One of the arms of the NCI-MATCH study from the BRAF V600E arm contributed towards the BRAF V600E tissue-agnostic approval. So, the BRAF V600E tissue-agnostic approval was by a pooled analysis of several studies. The ROAR study, the Rare Oncology Agnostic Research study, the NCI-MATCH dataset of tumor-agnostic cohort, and another pediatric trial, and also evidence from literature and evidence of case reports. And all this pooled analysis contributed to the tissue-agnostic approval of BRAF V600E across multiple rare cancers. There are several patient advocacy organizations which are the real unsung heroes here. Groups like, for instance, we mentioned in the paper, Target Cancer Foundation, don't just raise awareness for rare cancer research, they actively connect patients to trials providing financial, emotional support, and even run their own studies like the TRACK trial. They also influence policy to make access easier. On a global scale, initiatives like DRUP in the Netherlands, the ROME study in Italy, the PCM4EU in Europe are expanding precision medicine across these borders. These collaborations accelerate research, improve trial enrollment, and ensure patients everywhere can have access to these cutting-edge therapies. Again, it is truly a team effort, right? It is a multi-stakeholder approach. Researchers, clinicians, investigators, industry, regulators, academia, patients, patient advocates, and their caregivers all working together. And it takes a village. Dr. Hope Rugo: Absolutely. I mean, what a nice response to that. And I think really exciting and it is great to see your passion about this as well. But it helps all of us, I think, getting discouraged in treating these cancers to understand what is happening moving forward. And I think it is also a fabulous opportunity for our junior colleagues as they rise up in academics to be involved in these international collaborative efforts which are further expanding. One of the things that comes up for clinical trials for patients, and I think it is highlighted with rare cancers because, as you mentioned, people are all over the place, you know, they are so rare. They are all far away. Our patients are always saying to us, "Should I go here for a phase 1 trial?" Can you talk a little bit about how we can overcome these financial and geographic burdens for the patients? You talked about having trials locally, but it is a big financial and just social burden for patients. Dr. Vivek Subbiah: Great point. Financial cost is a major barrier in rare cancer clinical trials. It is a major barrier not just in rare cancer clinical trials, but in clinical trials in general. The economics of rare cancer research are one of the toughest challenges we face. Developing a new drug is already expensive, often billions of dollars. On an average, it takes 2 billion dollars or 2.8 billion dollars according to some data from drug discovery to approval. For rare cancers, the market is tiny, which means the pharmaceutical companies have really little financial incentive to invest. That is why initiatives like the Orphan Drug Act were created to provide tax credits, grants, and market exclusivity to encourage development for rare diseases. Clinical trials themselves are expensive because the small patient populations mean longer recruitment times and higher per-patient costs. Geographic dispersion, as you mentioned, for the patients adds travel, coordination. That is why we need to think out of the box about decentralized trial infrastructure so that we can mitigate some of these expenses. Complex trial designs like basket or platform trials sometimes require sophisticated data systems and regulatory oversight. That is a challenge. And I think some of the pragmatic studies like ASCO TAPUR have overcome those challenges. Advanced technologies like next-gen sequencing and molecular profiling also add significant upfront cost to this. Funding is also limited because rare cancers receive less attention compared to common cancers. Public funding and cooperative group trials help a lot, but I think they cannot cover everything. Patient advocacy organizations sometimes step in to bridge these gaps, but sustainable financing remains a huge challenge. So, the bottom line is without financial incentives and collaborating funding models, many promising therapies for rare cancers would never make it to patients. That is why we need system-wide policy changes, global partnerships, and innovative, effective, seamless trial designs which are so critical so that they can help reduce the cost and make research feasible so that we can deliver the right drug to the right patient at the right time. Dr. Hope Rugo: There is a lot of excitement about the future integration of AI in screening. Just at the San Antonio Breast Cancer meetings, we have a number of different presentations about AI to find markers, even like HER2, and using AI where you would screen and then match patients to clinical trials. Do you have any guidance for the rare cancer community on how to leverage this technology in order to optimize patient enrollment and, I think, identification of the best treatment matches? Dr. Vivek Subbiah: I think artificial intelligence, AI, is a game-changer in the making. Right now, clinical trial is clunky. Matching patients to trial is often manual, time consuming, laborious. You need a lot of personnel to do that. AI can automate this process by analyzing genomic data, medical records, and trial eligibility criteria to find the best matches quickly, accurately, and effectively. For the community, the key is to invest in data standardization and interoperability because AI needs clean, structured data to work effectively. Dr. Hope Rugo: Thank you so much, Dr. Subbiah, for sharing these fantastic insights with us on the podcast today and for your excellent article. Dr. Vivek Subbiah: Thank you so much. Dr. Hope Rugo: We thank you, our listeners, for joining us today. You will find a link to Dr. Subbiah's Educational Book article in the transcript of this episode. And please join us again next month on By the Book for more insightful views on key issues and innovations that are shaping modern oncology.  Thank you. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:        Dr. Hope Rugo   @hoperugo   Dr. Vivek Subbiah @VivekSubbiah Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:       Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx   Dr. Vivek Subbiah: Consulting/Advisory Role: Loxo/Lilly, Illumina, AADI, Foundation Medicine, Relay Therapeutics, Pfizer, Roche, Bayer, Incyte, Novartis, Pheon Therapeutics, Abbvie Research Funding (Inst.): Novartis, GlaxoSmithKline, NanoCarrier, Northwest Biotherapeutics, Genentech/Roche, Berg Pharma, Bayer, Incyte, Fujifilm, PharmaMar, D3 Oncology Solutions, Pfizer, Amgen, Abbvie, Mutlivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agensys, Idera, Boston Biomedical, Inhibrx, Exelixis, Amgen, Turningpoint Therapeutics, Relay Therapeutics Other Relationship: Medscape, Clinical Care Options

The current landscape of testing for NSCLC is complex, with many new biomarkers emerging rapidly, more points during which testing is possible, and precision drug treatments available on the basis of findings from biomarker testing. While promising for patients, the result of this rapidly changing landscape is confusion from interdisciplinary care teams as to what testing is necessary and when, who in multidisciplinary care teams should be ordering new tests and when, and what workflows are necessary for labs. Host David Ritter, MA is joined by Dr. Ying-Chun Lo and Dr. Mamatha Chivuluka to discuss what things pathologists and lab professionals need to know about emerging biomarkers for NSCLC. In this conversation, the panel reflects on how NSCLC biomarker testing has evolved over the past decade, highlighting the shift from limited, sequential testing to guideline-recommended broad molecular profiling. Drs. Lo and Chivuluka explore the clinical relevance of emerging biomarkers such as HER2, TROP2, and HER3, and discuss how new targeted therapies are influencing testing strategies in real-world practice. They also examine practical considerations for laboratories, including platform selection across IHC, PCR, and NGS, approaches to tissue stewardship in small lung biopsies, and the growing leadership role of pathologists in multidisciplinary teams to ensure timely, guideline-concordant, and equitable access to biomarker testing for patients with NSCLC. 

Featuring perspectives from Dr Javier Cortés, Dr Rita Nanda, Prof Peter Schmid and Dr Priyanka Sharma, including the following topics:  Introduction (0:00) Case: A woman in her early 80s with multiple comorbidities and triple-negative breast cancer (TNBC) develops bone-only metastases 4 months after declining capecitabine for post-neoadjuvant residual disease — Justin Favaro, MD, PhD (1:50) Case: A woman in her mid 70s with ER-negative, HER2-low (IHC 1+), PIK3CA-mutated, PD-L1-positive metastatic breast cancer (mBC) after receiving 3 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab, which was discontinued — Alan Astrow, MD (6:47) Previously Untreated Metastatic TNBC (mTNBC) — Prof Schmid (10:47)  Case: A woman in her early 80s with multiregimen-recurrent ER-positive, HER2-low (IHC 1+) ESR1-mutant mBC receives sacituzumab govitecan — Jennifer Yannucci, MD (27:19) Case: The role of datopotamab deruxtecan (Dato-DXd) for patients with ER-positive, HER2-low mBC who experienced disease progression on prior trastuzumab deruxtecan (T-DXd) — Ranju Gupta, MD; Case: A woman in her late 70s with bilateral recurrence in the lungs of ER-negative, HER2-low (IHC 1+) breast cancer (PD-L1 TPS 20%) receives Dato-DXd with durvalumab on protocol — Yanjun Ma, MD, PhD (31:35) Integrating Antibody-Drug Conjugates (ADCs) into the Management of Endocrine-Resistant Hormone Receptor-Positive mBC — Dr Sharma (36:31) Case: A woman in her early 70s with recurrent ER-negative, HER2-low (IHC 2+) mBC receives sacituzumab govitecan and achieves complete remission — Dr Gupta; Case: Management of neutropenia associated with sacituzumab govitecan — Gigi Chen, MD (50:30) Case: A woman in her late 60s with recurrent ER-negative, HER2-low (IHC 1+) mBC (HER2 V69L mutation) receives T-DXd and achieves a complete response but develops Grade 1 interstitial lung disease — Dr Gupta; Case: Management of T-DXd-related side effects — Laila Agrawal, MD (54:10) Selection and Sequencing of Therapy for Relapsed/Refractory mTNBC — Dr Nanda (58:59) Case: A woman in her early 40s with multiregimen-recurrent ER-positive, HER2-low mBC who has experienced severe nausea with past treatments is about to initiate T-DXd — Atif M Hussein, MD, MMM (1:12:40) Tolerability and Other Practical Considerations with ADCs and Other Cytotoxic Agents for mBC — Dr Cortés (1:18:10) CME information and select publications

Dr. Monty Pal and Dr. Hope Rugo discuss advances in antibody-drug conjugates for various breast cancer types as well as treatment strategies in the new era of oral SERDs for HR-positive breast cancer. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and vice chair of academic affairs here at the City of Hope Comprehensive Cancer Center, Los Angeles. Today, I'm thrilled to be joined by Dr. Hope Rugo, an internationally renowned breast medical oncologist and my colleague here at City of Hope, where she leads the Women's Cancers Program and serves as division chief of breast medical oncology. Dr. Rugo is going to share with us exciting advances in antibody-drug conjugates (ADCs) that are expanding treatment options in various breast cancer types. She'll also address some of the complex questions arising in the new era of oral SERDs (selective estrogen receptor degraders) that are revolutionizing treatment in the hormone receptor-positive breast cancer space. Our full disclosures are available in the transcript of this episode.  Dr. Rugo, welcome, and thanks so much for being on the podcast today. Dr. Hope Rugo: Thank you. Pleasure to be here. Dr. Monty Pal: So, I'm going to switch to first names if you don't mind.  The first topic is actually a really exciting one, Hope, and this is antibody-drug conjugates. I don't know if I've ever shared this with you, but I actually started my training at UCLA, I was a med student and resident there, and it was in Dennis Slamon's lab. I worked very closely with Mark Pegram and a handful of others. This is right around the time I think a lot of HER2-directed therapies were really evolving initially in the clinics. Now we've got antibody-drug conjugates. Our audience is well-familiar with the mechanism there but tell us about how ADCs have really started to reshape therapy for HER2-positive breast cancer. Dr. Hope Rugo: Yeah, I mean, this is a really great place to start. I mean, we have had such major advances in breast cancer just this year, I think really changing the paradigm of treating patients. But HER2-positive disease, we've been used to having sequenced success of new agents. And I think the two biggest areas where we've made advances in HER2-positive disease, which were remarkably advanced this year in 2025, have been in antibody-drug conjugates with trastuzumab deruxtecan and with new oral tyrosine kinase inhibitors (TKIs) that have less of a target on EGFR and more on HER2, so they have an overall more tolerable toxicity profile and therefore a potentially better efficacy in the clinic. At least that's what we're seeing with these new strategies that we couldn't really pursue in the past because of toxicities of the oral TKIs. So, although our topic is ADCs, I'm going to include the TKI because it's so important in our thinking about treating HER2-positive disease. In the metastatic setting, we've seen these remarkable improvements in progression-free and overall survival in the second-line setting with T-DXd, or trastuzumab deruxtecan, compared to T-DM1. And then sequencing ADCs with giving T-DXd after T-DM1 was better than an oral tyrosine kinase or a trastuzumab combination with standard chemotherapy. That was DESTINY-Breast03 and DESTINY-Breast02. So, then we've had other trials since then, and T-DXd has moved into the early-stage setting, which I'll talk about in just a moment. But the next big trial for T-DXd in HER2-positive disease was moving it to the first-line setting to supplant what has become an established treatment for now quite a long time: the so-called CLEOPATRA regimen, which used the combined antibodies trastuzumab, pertuzumab with a taxane as first-line therapy. And then we've proceeded on with maintenance with ongoing HP for patients with responding or stable disease. And we'd seen long-term data showing, you know, at 8 years there was a group of patients whose cancers had never progressed and continued improved overall survival. So, T-DXd was studied in DESTINY-Breast09, either alone or in combination with pertuzumab compared to THP. The patient population had received a little bit more prior treatment, but interestingly, not a lot compared to CLEOPATRA. And they designed the trial to be T-DXd continued until progression with or without pertuzumab versus THP, which would go for six cycles and then stop around six cycles, and then stop and continue HP. Patients who had hormone receptor-positive disease could use hormone therapy, and this is one of the issues with this dataset because, surprisingly in this dataset and one other I'll mention, very few patients took hormone therapy. And even in the maintenance trial, the HER2CLIMB-05, less than 50% took hormone therapy as maintenance. This is kind of shocking to me and highlights an area of really important education, that outcome is improved when you add endocrine therapy for hormone receptor-positive HER2-positive metastatic disease in the maintenance phase, and it's a really important part of treatment. But suffice it to say, you know, you're kind of studying continued chemo versus stopping chemo in maintenance. And T-DXd, as we all expected, in combination with pertuzumab was superior to THP in terms of progression-free survival, really remarkably improved. And you could stop the chemo with toxicity, but most people continued it with T-DXd. Again, not a lot of people got hormone therapy, which is an issue, and you stop the chemo in the control arm. So, this has brought up a lot of interest in trying to use T-DXd as an induction and then go to maintenance, much as we do with the CLEOPATRA regimen with hormone therapy. But it brings up another issue. So first, T-DXd is superior; it's a great treatment. Not everybody needs to have it because we don't know whether it's better to give T-DXd first or second with progression - that we need a little bit longer follow-up. But just earlier this week, interestingly, the third week of December, the U.S. FDA approved T-DXd in the DESTINY-Breast09 approach with pertuzumab. So as I mentioned earlier, there was a T-DXd-alone arm; that arm has not yet reported. So very interesting, we don't know if you need pertuzumab or not. So what about the maintenance? That's the other area where we've made a huge advance here. So, we all want to stop chemo and we want to stop T-DXd. You don't want somebody being nauseated for two years while they're on treatment, and also there's a small number of patients with mostly de novo metastatic HER2-positive disease who are cured of their disease. We'd like to expand that, and I think these new drugs give us the opportunity to improve the number of patients who might be cured from metastatic disease. So the first maintenance study we saw was adding palbociclib, the CDK4/6 inhibitor, to endocrine therapy and HP, essentially. There, we had a remarkable improvement in progression-free survival difference of 15.2 months: 29 to 44 months, really huge. At San Antonio this year, we saw data with this oral tyrosine kinase inhibitor tucatinib, already showed it was great in a triplet, but as maintenance in combination with HP, it showed also a remarkable improvement in progression-free survival. But the numbers were all shifted down. So in PATINA, the control arm was in the 24-month range; here it was the tucatinib-HP arm that was in the 25 months and 16 months for control. So there was a differential benefit in ER-negative and ER-positive disease. So I think we're all thinking that our ideal approach moving forward would be to give T-DXd to most patients, we see how they do, and treat to best response. And then, stop the T-DXd, start HP, trastuzumab, pertuzumab for ER-negative, with tucatinib for ER-positive with palbociclib. We also have early data that suggests that both approaches may reduce the development of brain metastases, an issue in HER2-positive disease, and delay time to progression of brain metastases as seen in HER2CLIMB-05 in very early data - small numbers, but still quite intriguing that you might delay progression of brain metastases with tucatinib that clearly has efficacy in the brain.  So, I think that this is a hugely exciting advance for our patients, and these approaches are quickly moving into the early stage setting. T-DXd compared to standard chemo, essentially followed by THP, so a sequenced approach resulted in more pathologic complete responses than a standard THP-AC-type neoadjuvant therapy. T-DXd alone for eight cycles wasn't better, and that's interesting. We still need the sequenced non-cross-resistant chemo. But I think even more importantly, the data from DESTINY-Breast05 looking at T-DXd versus T-DM1 in patients with residual disease after neoadjuvant HER2-targeted therapy showed a remarkable improvement in invasive disease-free survival with T-DXd versus T-DM1, and quite early. It was a high-risk population, higher risk than the T-DM1 trial with KATHERINE, but earlier readout with a remarkable improvement in outcome. We expect to be FDA approved sometime in the first half of 2026. So then we'll get patients who've already had T-DXd who get metastatic disease. But my hope is that with T-DXd, maybe with tucatinib in the right group of patients or even sequenced in very high-risk disease, that we could cure many more patients with early-stage HER2-positive breast cancer and cure a subset, a greater subset of patients with de novo metastatic disease. Dr. Monty Pal: That's brilliant. And you tackled so many questions that I was going to follow up with there: brain metastases, etc. That was sort of looming in my mind. I mean, general thoughts on an ADC versus a TKI in the context of brain mets? Dr. Hope Rugo: Yeah, it's an interesting question because T-DXd has shown quite good efficacy in this setting. And tucatinib, of course, had a trial where they took patients with new brain mets, so a larger population than we've seen yet for the T-DXd trials, and saw that not only did they delay progression of brain metastases and result in shrinkage of existing untreated brain mets, but that patients who develop a new brain met, they could stay on the same assigned treatment. They got stereotactic radiation, and then the patients who were on tucatinib with trastuzumab and capecitabine had a further delay in progression of brain mets compared to those on the placebo arm, even after treatment of a new one that developed on treatment. So, I think it's hard. I think most of us for a lot of brain mets might start with the tucatinib approach, but T-DXd is also a very important treatment. You know, you're kind of trading off a diarrhea, some liver enzyme elevations with tucatinib versus nausea, which you really have to work on managing because it can be long-delayed nausea, and this risk of ILD, interstitial lung disease, that's about 12%, with most but not all trials showing a mortality rate from interstitial lung disease of just under 1 percent. In the early-stage setting, it was really interesting to see that with T-DXd getting four cycles in the neoadjuvant setting, a lot less ILD noted than the patients who got up to 14 cycles, as I think they got a median of 10 cycles in the post-surgical setting, there was a little bit more ILD. But I think we're going to be better and better at finding this earlier and preventing mortality by just stopping drug and treating earlier with steroids. Dr. Monty Pal: And this ILD issue, it always seems to resurface. There are drugs that I use in my kidney cancer clinic, everolimus, common to perhaps the breast cancer clinic as well, pembrolizumab, where I think the pattern of pneumonitis is quite different, right? What is your strategy for recognizing pneumonitis early in this context? Dr. Hope Rugo: Well, it is, and you know, having done the very early studies in everolimus where we gave it in the neoadjuvant setting and we're like, "Hmm, the patient came in with a cough. What's going on?" You know, we didn't know. And you have mouth sores, you know, we were learning about the drug as we were giving it. What we don't do with everolimus and CDK4/6 inhibitors, for example, is grade 1 changes like radiation pneumonitis, we don't stop, we don't treat it. We only treat for symptoms. But because of the mortality associated with T-DXd, albeit small, we stop drug for grade 1 imaging-only asymptomatic pneumonitis, and some of us treat with a half dose of steroids just to try and hasten recovery. We've actually now published or presented a couple of datasets from trials, a pooled analysis and a real-world analysis, that have looked at patients who were retreated after grade 1 pneumonitis or ILD and tolerated drug very well and none of them died of interstitial lung disease, which was really great to see because you can retreat safely and some of these patients stayed on for almost a year benefiting from treatment. So, there's a differential toxicity profile with these drugs and there are risk factors which clearly have identified those at higher risk: prior ILD, for example. A French group said smoking; other people haven't found that, maybe because they smoked more in France, I don't know. And being of Japanese descent is quite interesting. The studies just captured that you were treated in Japan, but I think it's probably being of Japanese descent with many drugs that increases your risk of ILD. And, you know, older patients, people who have hypoxia, those are the patients. So, how do we do this? With everolimus, we don't have specific monitoring. But for T-DXd we do; we do every nine weeks to start with and then every 12 weeks CT scans because most of the events occur relatively early. Somebody who's older and at higher risk now get the first CT at six weeks. Dr. Monty Pal: This is super helpful. And I have to tell you, a lot of these drugs are permeating the bladder cancer space which, you know, is ultimately going to be a component of my practice, so thank you for all this. We could probably stay on this topic of HER2-positive disease forever. I'm super interested in that space still. But let me shift gears a little bit and talk about triple-negative breast cancer and this evolving space of HR-positive, HER2-low breast cancer. I mean, tell us about ADCs in that very sort of other broad area. Dr. Hope Rugo: So triple-negative disease is the absolute hardest subset of disease that we have to treat because if you don't have a great response in the early stage setting, the median survival is very short, you know, under two years for the majority of TNBCs, with the exception of the small percentage of low proliferative disease subsets. The co-question is what do we do for these patients and how do we improve outcome? And sacituzumab govitecan has been one strategy in the later line setting that was shown to improve progression-free and overall survival, the Trop-2 ADC. We had recently three trials presented with the two ADCs, sacituzumab govitecan and the other Trop-2 ADC that's approved for HR-positive disease, datopotamab deruxtecan. And they were studied in the first-line setting. Two trials with SG, sacituzumab govitecan, those trials, one was PD-L1 positive, ASCENT-04. That showed that SG with a checkpoint inhibitor was superior, so pembrolizumab was superior to the standard KEYNOTE-355 type of treatment with either a taxane or gemcitabine and carboplatin with pembrolizumab for patients who have a combined positive score for PD-L1, 10 or greater. So, these are patients who are eligible for a checkpoint inhibitor, and SG resulted in an improved progression-free survival.  The interesting thing about that dataset is that few patients had received adjuvant or neoadjuvant checkpoint inhibitor, which is fascinating because we give it to everybody now. But access is an issue and timing of the study enrollment was an issue. The other thing which I think we've all really applauded Gilead for is that there was automatic crossover. So, you could get from the company, to try and overcome some of the enormous disparities worldwide in access to these life-saving drugs, you could get SG through the company for free once you had blinded independent central review confirmation of disease progression. Now, a lot of the people who got the SG got it through their insurance, they didn't bill the company, but 80 percent of patients in the control arm received SG in the second-line setting. So that impacts your ability to look at overall survival, but it's an incredibly important component of these trials. So then at ESMO, we saw the data from SG and Dato-DXd in the first-line metastatic setting for patients who either had PD-L1-negative disease or weren't eligible for an immunotherapy. For the Dato study, TROPION-Breast02, that was 10 percent of the patients who had PD-L1-positive disease but didn't get a checkpoint inhibitor, and for the ASCENT-03 trial population it was only 1 percent. Importantly, the trials allowed patients who relapsed within a year of receiving their treatment with curative intent, and the Dato study, TB-02, allowed patients who relapsed while on treatment or within the first six months, and that was 15 percent of the 20 percent of early relapsers. The ASCENT trial, ASCENT-03, had 20 percent who relapsed between 6 and 12 months. The drugs were better than standard of care chemotherapy, the ADCs in both trials, which is very nice. Different toxicity profiles, different dosing intervals, but better than standard of care chemotherapy in the disease that's hardest for us to treat. And importantly, when you looked at the subset of early relapsers, those patients also did better with the ADC versus chemotherapy, which is incredibly important. And we were really interested in that 15 percent of patients who had early relapse. I actually think that six months thing was totally contrived, invented, you know, categorization and doesn't make any sense, and we should drop it. But the early relapsers were 15 percent of TB-02 and Dato was superior to standard of care chemo. We like survival, but the ASCENT trial again allowed the crossover to an approved ADC that improved survival and 80 percent of patients crossed over. In the Dato trial, they did not allow crossover, they didn't provide Dato, which isn't approved for TNBC but is for HR-positive disease, and they didn't allow, of course, pay for SG. So very few patients actually crossed over in their post-treatment data and in that study, they were able to show a survival benefit. So actually, I think in the U.S. where we can use approved drugs already before there's a fixed FDA approval, that people are already switching to use SG or Dato in the first-line setting for metastatic TNBC that's both PD-L1 positive for SG and PD-L1 negative for both drugs. And I think understanding the toxicity profiles of the two drugs is really important as well as the dosing interval to try and figure out which drug to use. Dr. Monty Pal: Brilliant. Brilliant. Well, I'm going to shift gears a little bit. ADCs are a topic, again, just like HER2-positive disease we could stay on forever. Dr. Hope Rugo: Huge. Yes. Dr. Monty Pal: But we're going to shift gears to another massive topic, which is oral SERDs. In broad strokes, right, this utilization of CDK4/6 inhibitors in the context of HR-positive breast cancer is obviously, you know, a paradigm that's been well established at this point. Where do we sequence in oral SERDs? Where do they fit into this paradigm? Dr. Hope Rugo: Ha! This is a rapidly changing area; we keep changing what we're saying every other minute. And I think that there are three areas of great interest. So one is patients who develop ESR1 mutations that allow constitutive signaling through the estrogen receptor, even when there's not estrogen around, and that is a really important mutation that is subclonal; it develops under the pressure of treatment in about 40 percent of patients. And it doesn't happen when you first walk in the door. And what we've seen is that oral SERDs as single agents are better than standard single-agent endocrine therapy in that setting. The problem that we've had with that approach is that we're now really interested in giving targeted agents with our endocrine therapies, not just in the first-line setting where CDK4/6 inhibitors are our standard of care with survival benefit for ribociclib and, you know, survival benefit in subsets with other CDK4/6 inhibitors, and abemaciclib with a numeric improvement. So we give it first line. The question is, what do you do in the second-line setting? Because of the recent data, we now believe that oral SERDs should be really given with a targeted agent. And some datasets which were recently presented, which I think have helped us with that, have been EMBER-3 and then the most recently evERA BC, or evERA Breast Cancer, that looked at the oral SERD giredestrant with everolimus compared to standard of care endocrine therapy with everolimus, where 100 percent of patients received prior CDK4/6 inhibitor and showed a marked improvement in progression-free survival, including in the subsets of patients with a short response, 6-12 months of prior response to CDK4/6 inhibitor and in those who had a PIK3CA pathway mutation. The thing is that the benefit looks like it's much bigger in the ESR1 mutant population, although response was better, PFS wasn't better in the wild type. So, we're still trying to figure that out. We also saw EMBER-3 with imlunestrant and abemaciclib as a second line. Not everybody had had a prior CDK4/6 inhibitor; they compared it to imlunestrant alone, but still the data was quite striking and seemed to cross the need for ESR1 mutations. And then lastly, we saw data from the single arms of the ELEVATE trial looking at elacestrant with everolimus and abemaciclib and showed these really marked progression-free survival data, even though single-arm, that crossed the mutation status. At least for the everolimus combination, abemaciclib analysis is still to come in the mutated subgroups. But really remarkable PFS, much longer.  Single-agent fulvestrant after CDK4/6 inhibitor AI has a PFS in like the three-month range and in some studies, maybe close to five months. These are all at 10-plus months and really looking very good. And so those questions are, is it ESR1 mutation alone? Is it all comers? We'd like all comers, right? We believe in the combination approach and we're learning more about combinations with drugs like capivasertib and other drugs as we move forward. Everybody now wants to combine their targeted agent with an oral SERD because they're clearly here to stay with quite remarkable data. The other issue, so the second issue in the metastatic setting is, does it make a difference if we change to an oral SERD before radiographic imaging evidence of progression? And that was the question asked in the SERENA-6 trial where patients had serial monitoring for the presence of ESR1 mutations in ctDNA. And those who had them without progression on imaging could be randomized to switch to camizestrant with the same CDK4/6 inhibitor or stay on their same AI CDK4/6 inhibitor. And they showed a difference in progression-free survival that markedly favored camizestrant. But interestingly, the people who were on the standard control arm had an ESR1 mutation, we think AIs don't work, they stayed on for nine more months. The patients who were on the camizestrant stayed on for more than 16 months. And they presented some additional subset data which showed the same thing: follow-up PFS data, PFS2, all beneficial in SERENA-6 at the San Antonio [Breast Cancer Symposium]. So, we're still a little bit unclear about that. They did quality of life, and pain was markedly improved. They had a marked delayed time to progression of pain in the camizestrant arm. So this is all a work in progress, trying to understand who should we switch without progression to an oral SERD based on this development of this mutation that correlates with resistance. And, you know, it's interesting because the median time to having a mutation was 18 months and the median time to switch was almost 24 months. And then there were like more than 3,000 patients who hadn't gotten a mutation, hadn't switched, and were still okay. So screening everybody is the big question, and when you would start and who you would change on and how this affects outcome. Patients didn't have access to camizestrant in the control arm, something we can't fix but we have experimental drugs. We're actually planning a trial, I hope in collaboration with the French group Unicancer, and looking at this exact question. You know, if you switch and you change the CDK4/6 inhibitor and then you also allow crossover, what will we see? Dr. Monty Pal: We're coming right to the tail end of our time here, and I could probably go on for another couple of hours with you here. But if you could just give us maybe one or two big highlights from San Antonio, any thoughts to leave our audience with here based on this recent meeting? Dr. Hope Rugo: Yeah, I mean, I talked about a lot of those new data already from San Antonio, and the one that I'd really like to mention which I think was, you know, there were a lot of great presentations including personalized screening presented from the WISDOM trial by my colleague Laura Esserman, fascinating and really a big advance. But lidERA was the big highlight, I think, outside of the HER2CLIMB-05 which I talked about earlier in HER2-positive disease. And this study looked at giredestrant, the oral SERD versus standard of care endocrine therapy as treatment for medium and high-risk early-stage breast cancer. And what they showed, which I think was really remarkable with just about a three-year median follow-up, was an improvement in invasive disease-free survival with a hazard ratio of 0.7. I mean, really quite remarkable and so early. It looked as though this was all driven by the high-risk group, which makes sense, not the medium risk, it's too early. And also that there was a bigger benefit in patients who were on tamoxifen compared to giredestrant versus AI, but for both groups, the confidence intervals didn't cross 1. There's even a trend towards overall survival, even though it's way too early. I think that, you know, really well-tolerated oral drug that could improve outcome in early-stage disease, this is the first advance we've seen in over two decades in the treatment of early-stage hormone receptor-positive disease with just endocrine therapy. I think we think that we don't want to give up CDK4/6 inhibitors because we saw a survival benefit with abemaciclib and a trend with giving ribociclib in the NATALEE trial. So we're thinking that maybe one approach would be to give CDK4/6 inhibitors and then switch to an oral SERD or to have enough data to be able to give oral SERDs with these CDK4/6 inhibitors for early-stage disease. And that's all in the works, you know, lots of studies going on. We're going to see a lot of data with both switching 8,000 patients with an imlunestrant switching trial, an elacestrant trial going on, and safety data with giredestrant with abemaciclib and soon to come ribociclib. So, this is going to change everything for the treatment of early-stage breast cancer, and I hope cure more patients of the most common subset of the most common cancer diagnosed in women worldwide. Dr. Monty Pal: Super exciting. It's just remarkable to hear how this has evolved since 25 years ago, which is really the last time I sort of dabbled in breast cancer.  Thank you so much, Hope, for joining us today. These were fantastic insights. Appreciate you being on the ASCO Daily News Podcast and really want to thank you personally for your remarkable contribution to the field of breast cancer. Dr. Hope Rugo: Thank you very much, and thanks for talking with me today. Dr. Monty Pal: You got it. And thanks a lot to our listeners today as well. You'll find links to all the studies we discussed today in the transcript of this episode. Finally, if you value the insights that you hear today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinion of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:   Dr. Monty Pal @montypal Dr. Hope Rugo   @hoperugo Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:     Dr. Monty Pal:    Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview   Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical   Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  

Join us as we dive into the latest advancements in HER2-positive breast cancer from SABCS 2025. In this episode, we discussed key studies including DESTINY Breast-11 and DESTINY Breast-05, highlighting their implications for neoadjuvant and adjuvant treatments. We also explored the HER2CLIMB-05 trial and the recent approval of TDXD with pertuzumab in frontline settings for metastatic HER2-positive disease. Special guest Dr. Harold Burstein from Dana-Farber Cancer Institute shared his insights on the evolving landscape of HER2-positive breast cancer treatment, including the importance of patient selection and the management of side effects like interstitial lung disease (ILD). Tune in for a comprehensive recap of the latest data, treatment algorithms, and how these advancements are changing the lives of patients with HER2-positive breast cancer. Don't forget to like, subscribe, and check out our other episodes for more updates on treatment options and conference highlights! Topics Covered: • DESTINY Breast-11 and its impact on neoadjuvant therapy • Insights from DESTINY Breast-05 on adjuvant treatment for high-risk residual disease • HER2CLIMB-05 trial findings and implications for metastatic disease • The role of T-DXd with pertuzumab in frontline settings • The PATINA trial and its significance for triple-positive metastatic breast cancer Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more insights on treatment algorithms, recent approvals, and conference highlights! #SABCS2025 #HER2positive #DestinyTrials #OncologyBrothers #BreastCancer

Drs. Yu and Herzberg discuss recent developments in HER2- and EGFR-targeted therapies for lung cancer, focusing on clinical trial results at ESMO 2025. Key highlights include promising response rates, toxicity profiles, and the potential for these targeted therapies to treat patients with specific genetic mutations, particularly those with CNS metastases.

Drs. Herzberg and Yu continue their discussion on emerging clinical data presented at ESMO and WCLC 2025. They highlight recent advancements in HER2-targeted therapies for NSCLC and review new HER2-targeted therapies, international study results, and the promise of evolving targeted approaches for HER2-altered lung cancer.

Are you up to date on the evolving treatment landscape for HER2-mutated non-small cell lung cancer (NSCLC)? Do you know the role of novel targeted therapies? Credit available for this activity expires: 12/24/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/precision-oncology-her2-mutated-nsclc-strategies-today-and-2025a100105r?ecd=bdc_podcast_libsyn_mscpedu

Drs. Herzberg and Yu explore emerging clinical data from the 2025 meetings of the European Society For Medical Oncology (ESMO) and World Conference on Lung Cancer (WCLC), highlighting recent advancements in HER2-targeted therapies for NSCLC. Their discussion focuses on new drugs (eg, zongertinib and trastuzumab deruxtecan), their efficacy and safety profiles, and the potential for treating HER2 mutations and overexpression.

In this episode, Dr John Heymach and Dr Solange Peters discuss key data presented at the IASLC World Conference on Lung Cancer including first-line maintenance in ES-SCLC (IMforte and DeLLphi-303 trials) and targeted treatment for NSCLC (FLAURA2, Beamion LUNG-1, and ARROS-1 trials).Presenters:John Heymach, MD, PhDChair and ProfessorDepartment of Thoracic/Head and Neck Medical OncologyRuth Legett Jones Distinguished ChairMD Anderson Cancer CenterHouston, TexasSolange Peters, MD, PhD Professor and Director of Medical OncologyDepartment of OncologyUniversity Hospital of LausanneLausanne, SwitzerlandContent based on an online CME program supported by independent educational grants from Boehringer Ingelheim Pharmaceuticals, Inc. and Jazz Pharmaceuticals, Inc.Link to full program: https://bit.ly/3L1eksIGet access to all of our new podcasts by subscribing to the CCO Infectious Disease Podcast on Apple Podcasts, YouTube Music, or Spotify. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Featuring perspectives from Dr Lisa A Carey and Dr Rita Nanda, including the following topics:  Overview: Molecular basis of antibody-drug conjugate (ADC) toxicities — Sequencing of ADCs and mechanisms of resistance (0:00) Case: A woman in her late 60s with localized triple-negative breast cancer develops myocarditis during neoadjuvant therapy with chemotherapy/pembrolizumab — Richard Zelkowitz, MD (8:22) Case: A woman in her mid 70s with recurrent ER-negative, HER2-low, PD-L1-positive metastatic breast cancer (mBC) who experiences disease progression on nab paclitaxel/atezolizumab responds to sacituzumab govitecan — Ranju Gupta, MD (26:43) Case: A woman in her early 80s with recurrent ER-positive, HER2-low (IHC 1+) mBC experiences disease progression on trastuzumab deruxtecan (T-DXd), then receives datopotamab deruxtecan and develops pulmonary symptoms — Laila Agrawal, MD (32:11) Data Review: T-DXd (37:51) Case: A woman in her early 70s with recurrent ER-positive, HER2-low (IHC 1+) mBC, including bladder metastases, experiences disease progression after palbociclib/letrozole, then capivasertib/fulvestrant, then nab paclitaxel — Justin Favaro, MD, PhD (44:02) Case: A woman in her late 70s with ER-positive, HER2-low mBC who experiences disease progression after 1 year of ribociclib/letrozole receives sacituzumab govitecan — Erik Rupard, MD (55:19) CME information and select publications

Featuring perspectives from Dr Yelena Y Janjigian, including the following topics: Introduction (0:00) Case: A man in his early 60s with a history of Barrett's esophagus presents with HER2-positive metastatic esophageal adenocarcinoma and a PD-L1 combined positive score (CPS) of 3 — Jennifer Yannucci, MD (10:20) Case: A man in his early 60s with multiregimen-recurrent HER2-positive gastroesophageal junction (GEJ) adenocarcinoma (claudin 18.2-positive, PD-L1 CPS 0) — Neil Morganstein, MD (14:53) Case: A woman in her early 80s with dementia and newly diagnosed mismatch repair-deficient, PD-L1-positive metastatic GEJ adenocarcinoma — Brian P Mulherin, MD (25:55) Case: A man in his mid 60s with localized HER2-negative GEJ cancer (PD-L1 CPS 2, claudin 18.2-positive) and residual disease after receiving neoadjuvant chemoradiation therapy and undergoing surgery — Stephen "Fred" Divers, MD (32:18) Case: A man in his early 80s with metastatic recurrence of esophageal adenocarcinoma and a PD-L1 total proportion score of 75% 2 years after resection of localized disease — Susmitha Apuri, MD (40:28) Case: A man in his mid 70s with claudin 18.2-positive metastatic esophageal adenocarcinoma who develops progressive toxicities with FOLFOX and zolbetuximab — Sean Warsch, MD (52:54) CME information and select publications

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. In the ever-evolving landscape of pharmaceuticals and biotechnology, a series of strategic transactions and scientific advancements are reshaping the industry.BioMarin's acquisition of Amicus Therapeutics for $4.8 billion is a significant highlight, marking the company's largest transaction to date. This move signifies a strategic pivot towards enhancing its capabilities in the rare disease sector, leveraging Amicus's expertise and robust pipeline to potentially improve patient outcomes in this highly specialized area. This acquisition is expected to enrich BioMarin's portfolio significantly with promising assets from Amicus, reflecting a strategic shift under new leadership towards rare disease treatments.Regulatory affairs have seen considerable activity as well, with the FDA raising concerns over manufacturing practices at Catalent's gene therapy facility. These issues, documented in a Form 483 following inspections, particularly pertain to the production of Elevidys. Such regulatory scrutiny emphasizes the critical importance of maintaining compliance with manufacturing standards in gene therapy—a burgeoning field within biotech that holds immense promise for treating genetically-driven conditions.The FDA's oversight extends beyond manufacturing practices to advertising, as evidenced by an untitled letter issued to Bristol Myers Squibb regarding their Cobenfy TV ad. This action is part of the FDA's broader initiative to ensure that direct-to-consumer marketing materials accurately portray drug benefits and risks, thereby protecting public health.In another strategic move, Alvotech and Teva are gearing up for the 2026 U.S. launch of an Eylea biosimilar following a settlement with Regeneron. This development highlights the competitive dynamics within the biosimilar market—a segment poised for growth as patents on major biologics expire, offering more cost-effective alternatives and expanding treatment access.Meanwhile, Clovis Oncology has achieved a milestone with Rubraca, which transitioned from accelerated approval to full FDA endorsement for prostate cancer treatment after five years. This progression underscores Rubraca's demonstrated efficacy and safety profile in addressing advanced prostate cancer—a notable achievement amid an increasingly competitive oncology market.Policy changes proposed by Health and Human Services Secretary Robert F. Kennedy Jr. could have profound implications by disrupting funding streams for hospitals providing gender-affirming care to minors. The potential impact on healthcare providers and patients who rely on these services is significant.Turning to clinical trials, Daiichi Sankyo has seen success with Enhertu receiving FDA approval for first-line HER2-positive breast cancer treatment. Nonetheless, challenges persist as a separate phase 3 trial for another antibody-drug conjugate was paused due to unexpected patient deaths. Meanwhile, Takeda plans to seek FDA approval for its TYK2 inhibitor following successful phase 3 trials in psoriasis—indicating promising potential in autoimmune disease therapies.Strategic shifts are evident across organizations as well, highlighted by Kathy Fernando's departure from Pfizer to join Replicate Bioscience as Chief Business Officer. Her new role focuses on advancing Replicate's self-replicating RNA technology platform—an area gaining traction due to its implications for vaccine development and therapeutic applications.On the clinical trials front, Altimmune reported encouraging results from a 48-week study on metabolic dysfunction-associated steatohepatitis (MASH). Their GLP-1/glucagon dual receptor agonist demonstrated sustained weight loss and improvements in non-invasive liver fibrosis measures—offering new hope for MASH patients who face limited treSupport the show

In this episode of the Oncology Brothers podcast, we are joined by Dr. Komal Jhaveri, a breast medical oncologist at Memorial Sloan Kettering, to discuss the evolving landscape of metastatic hormone receptor positive breast cancer, particularly focusing on low and ultra-low HER2 expression. Key topics include: • The significance of the DESTINY Breast-04 and DESTINY Breast-06 studies and their impact on treatment options. • The definition and implications of low and ultra-low HER2 expression in clinical practice. • The importance of HER2 testing and the dynamic nature of HER2 expression in tumors. • Treatment sequencing strategies, including the use of antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (TDXd) and sasituzumab govitecan. • Management of treatment-related toxicities, including ILD, nausea, and alopecia. Join us for an insightful discussion that aims to keep healthcare professionals updated on the latest advancements in cancer care. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for more episodes and insights!

Ready to close the gap in HER2-mutant NSCLC care? Join Memorial Sloan Kettering experts Helena A. Yu, MD, and Maria Arcila, MD, for a live webinar on optimizing HER2 testing and integrating the latest targeted therapies into your practice. They'll walk through how to improve detection and ensure your patients are getting the most effective, up-to-date treatments available. You can catch the live session on either of these dates: Wednesday, January 8 at 5:00 pm ET: https://bit.ly/4iZxnA0 Monday, January 26 at 5:00 pm ET: https://bit.ly/4qALw9J

Welcome back to the Oncology Brothers podcast! In this episode, we continue the CME series on HER2-positive GEJ and gastric cancer, shifting focus to the essential topic of treatment toxicity management. We're joined by two leading experts: Dr. Geoffrey Ku from Memorial Sloan Kettering and Dr. Shruti Patel from Stanford University. Building on their previous discussion of upper GI treatment algorithm with Dr. Rutika Mehta, this episode delves into the practical realities of managing patients on complex regimens. Drs. Ku & Patel break down the side effect profiles across the treatment continuum—from frontline trastuzumab-based combinations to emerging therapies like zanidatamab—and provide actionable strategies for community oncologists. Episode Highlights: • Practical management of frontline side effects with FOLFOX/XELOX chemotherapy plus trastuzumab and pembrolizumab • Reality check on trastuzumab cardiotoxicity: incidence rates and monitoring protocols in gastric vs. breast cancer • Immune-related adverse events with checkpoint inhibitors: what's common vs. rare in GI cancers • Critical insights on zanidatamab's synergistic diarrhea toxicity and mandatory prophylaxis strategies • TDXd (Enhertu) in second-line: moving beyond ILD fears to address frequent cytopenias and marrow management • Expert consensus on infusion reaction management for novel biologics • The importance of managing baseline symptoms in patients with dysphagia and nausea This episode bridges the gap between trial data and clinical practice, offering real-world wisdom on keeping patients on effective therapies through proactive toxicity management. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for our complete CME series covering treatment algorithms, FDA approvals, and practical management strategies! Accreditation/Credit Designation Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians' Education Resource®, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Acknowledgment of Commercial Support This activity is supported by an educational grant from Jazz Pharmaceuticals, Inc. Link to gain CME credits from this activity: https://www.gotoper.com/courses/navigating-the-adverse-event-landscape-in-her2-gea-therapy

JCO PO author Dr. Shilpa Gupta at Cleveland Clinic Children's Hospital shares insights into her article, "Fibroblast Growth Factor Receptor 3 (FGFR3) Alteration Status and Outcomes on Immune Checkpoint Inhibitors (ICPI) in Patients with Metastatic Urothelial Carcinoma". Host Dr. Rafeh Naqash and Dr. Gupta discuss how FGFR3 combined with TMB emerged as a biomarker that may be predictive for response to ICPI in mUC. TRANSCRIPT Dr. 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. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center. Today I am excited to be joined by Dr. Shilpa Gupta, Director of Genitourinary Medical Oncology at the Cancer Institute and co-leader of the GU Oncology Program at the Cleveland Clinic, and also lead author of the JCO PO article titled "Fibroblast Growth Factor Receptor 3 Alteration Status and Outcomes on Immune Checkpoint Inhibitors in Patients With Metastatic Urothelial Carcinoma." At the time of this recording, our guest's disclosures will be linked in the transcript. Shilpa, welcome again to the podcast. Thank you for joining us today. Dr. Shilpa Gupta: Thank you, Rafeh. Honor to be here with you again. Dr. Rafeh Naqash: It is nice to connect with you again after two years, approximately. I think we were in our infancy of our JCO PO podcast when we had you first time, and it has been an interesting journey since then. Dr. Shilpa Gupta: Absolutely. Dr. Rafeh Naqash: Well, excited to talk to you about this article that you published. Wanted to first understand what is the genomic landscape of urothelial cancer in general, and why should we be interested in FGFR3 alterations specifically? Dr. Shilpa Gupta: Bladder cancer or urothelial cancer is a very heterogeneous cancer. And while we find there is a lot of mutations can be there, you know, like BRCA1, 2, in HER2, in FGFR, we never really understood what is driving the cancer. Like a lot of old studies with targeted therapies did not really work. For example, we think VEGF can be upregulated, but VEGF inhibitors have not really shown definite promise so far. Now, FGFR3 receptor is the only therapeutic target so far that has an FDA approved therapy for treating metastatic urothelial cancer patients, and erdafitinib was approved in 2019 for patients whose tumors overexpressed FGFR3 mutations, alterations, or fusions. And in the landscape of bladder cancer, it is important because in patients with non-muscle invasive bladder cancer, about 70 to 80% patients can have this FGFR3. But as patients become metastatic, the alterations are seen in, you know, only about 10% of patients. So the clinical trials that got the erdafitinib approved actually used archival tumor from local cancer. So when in the real world, we don't see a lot of patients if we are trying to do metastatic lesion biopsies. And why it is important to know this is because that is the only targeted therapy available for our patients right now. Dr. Rafeh Naqash: Thank you for giving us that overview. Now, on the clinical side, there is obviously some interesting data for FGFR3 on the mutation side and the fusion side. In your clinical practice, do you tend to approach these patients differently when you have a mutation versus when you have a fusion? Dr. Shilpa Gupta: We can use the treatment regardless of that. Dr. Rafeh Naqash: I recently remember I had a patient with lung cancer, squamous lung cancer, who also had a synchronous bladder mass. And the first thought from multiple colleagues was that this is metastatic lung. And interestingly, the liquid biopsy ended up showing an FGFR3-TACC fusion, which we generally don't see in squamous lung cancers. And then eventually, I was able to convince our GU colleagues, urologists, to get a biopsy. They did a transurethral resection of this tumor, ended up being primary urothelial and synchronous lung, which again, going back to the FGFR3 story, I saw in your paper there is a mention of FGFR3-TACC fusions. Anything interesting that you find with these fusions as far as biology or tumor behavior is concerned? Dr. Shilpa Gupta: We found in our paper of all the patients that were sequenced that 20% had the pathognomonic FGFR3 alteration, and the most common were the S249C, and the FGFR3-TACC3 fusion was in 45 patients. And basically I will say that we didn't want to generate too much as to fusion or the differences in that. The key aspect of this paper was that historically there were these anecdotal reports saying that patients who have FGFR alterations or mutations, they may not respond well to checkpoint inhibitors because they have the luminal subtype. And these were backed by some preclinical data and small anecdotal reports. But since then, we have seen that, and that's why a lot of people would say that if somebody's tumor has FGFR3, don't give them immunotherapy, give them erdafitinib first, right? So then we had this Phase 3 trial called the THOR trial, which actually showed that giving erdafitinib before pembrolizumab was not better. That debunked that myth, and we are actually reiterating that because in our work we found that patients who had FGFR3 alterations or fusions, and if they also have TMB-high, they actually respond very well to single agent immunotherapy. And that is, I think, very important because it tells us that we are not really seeing that so-called potential of resistance to immunotherapy in these patients. So to answer your question, yeah, we did see those differences, but I wouldn't say that any one marker is more prominent. Dr. Rafeh Naqash: The analogy is kind of similar to what we see in lung cancer with these mutations called STK11/KEAP1, which are also present in some other tumors. And one of the questions that I don't think has been answered is when you have in lung cancer, if you extrapolate this, where doublet or single agent immunotherapy doesn't do as well in tumors that are STK11 mutated. But then if you have a high TMB, question is does that TMB supersede or trump the actual mutation? Could that be one reason why you see the TMB-high but FGFR3 altered tumors in your dataset responding or having better outcomes to immunotherapy where potentially there is just more neoantigens and that results in a more durable or perhaps better response to checkpoint therapy? Dr. Shilpa Gupta: It could be. But you know, the patients who have FGFR alterations are not that many, right? So we have already seen that just patients with TMB-high respond very well to immunotherapy. Our last podcast was actually on that, regardless of PD-L1 that was a better predictor of response to immunotherapy. So I think it's not clear if this is adding more chances of response or not, because either way they would respond. But what we didn't see, which was good, that if they had FGFR3, it's not really downplaying the fact that they have TMB-high and that patients are not responding to immunotherapy. So we saw that regardless, and that was very reassuring. Dr. Rafeh Naqash: So if tomorrow in your clinic you had an individual with an FGFR3 alteration but TMB-high, I guess one could be comfortable just going ahead with immunotherapy, which is what the THOR trial as you mentioned. Dr. Shilpa Gupta: Yes, absolutely. And you know, when you look at the toxicity profiles of pembrolizumab and erdafitinib, really patients really struggle with using the FGFR3 inhibitors. And of course, if they have to use it, we have to, and we reserve it for patients. But it's not an easy drug to tolerate. Currently the landscape is such that, you know, frontline therapy has now evolved with an ADC and immunotherapy combinations. So really if patients progress and have FGFR3 alterations, we are using erdafitinib. But let's say if there were a situation where a patient has had chemotherapy, no immunotherapy, and they have FGFR3 upregulation and TMB-high, yes, I would be comfortable with using only pembrolizumab. And that really ties well together what we saw in the THOR trial as well. Dr. Rafeh Naqash: Going to the clinical applications, you mentioned a little bit of this in the manuscript, is combination therapies. You alluded to it a second back. Everything tends to get combined with checkpoint therapy these days, as you've seen with the frontline urothelial, pembrolizumab with an ADC. What is the landscape like as far as some of these FGFR alterations are concerned? Is it reasonable to combine some of those drugs with immune checkpoint therapy? And what are some of the toxicity patterns that you've potentially seen in your experience? Dr. Shilpa Gupta: So there was indeed a trial called the NORSE trial. It was a randomized trial but not a comparative cohort, where they looked at FGFR altered patients. And when they combined erdafitinib plus cetrelimab, that did numerically the response rates were much higher than those who got just erdafitinib. So yeah, the combination is definitely doable. There is no overlapping toxicities. But unfortunately that combination has not really moved forward to a Phase 3 trial because it's so challenging to enroll patients with such kind of rare mutations on large trials, especially to do registration trials. And since then the frontline therapy has evolved to enfortumab vedotin and pembrolizumab. I know there is an early phase trial looking at a next generation FGFR inhibitor. There is a triplet combination looking in Phase 1 setting with a next generation FGFR inhibitor with EV-pembro. However, it's not a randomized trial. So you know, I worry about such kinds of combinations where we don't have a path for registration. And in the four patients that have been treated, four or five patients in the early phase as a part of basket trial, the toxicities were a lot, you know, when you combine the EV-pembro and an FGFR3 inhibitor, we see more and more toxicity. So the big question is do we really need the "kitchen sink" approach when we have a very good doublet, or unless the bar is so high with the doublet, like what are we trying to add at the expense of patient toxicity and quality of life is the big question in my mind. Dr. Rafeh Naqash: Going back to your manuscript specifically, there could be a composite biomarker. You point out like FGFR in addition to FGFR TMB ends up being predictive prognostic there. So that could potentially be used as an approach to stratify patients as far as treatment, whether it's a single agent versus combination. Maybe the TMB-low/FGFR3 mutated require a combination, but the TMB-high/FGFR mutated don't require a combination, right? Dr. Shilpa Gupta: No, that's a great point, yeah. Dr. Rafeh Naqash: But again, very interesting, intriguing concepts that you've alluded to and described in this manuscript. Now, a quick take on how things have changed in the bladder cancer space in the last two years. We did a podcast with you regarding some biomarkers as you mentioned two years back. So I really would like to spend the next minute to two to understand how have things changed in the bladder cancer space? What are some of the exciting things that were not there two years back that are in practice now? And how do you anticipate the next two years to be like? Maybe we'll have another podcast with you in another two years when the space will have changed even more. Dr. Shilpa Gupta: Certainly a lot has happened in the two years, you know. EV-pembro became the universal frontline standard, right? We have really moved away from cisplatin eligibility in metastatic setting because anybody would benefit from EV-pembro regardless of whether they are candidates for cisplatin or not, which historically was relevant. And just two days ago, we saw that EV-pembro has now been approved for localized bladder cancer for patients who are cisplatin ineligible or refusing. So, you know, this very effective regimen moving into earlier setting, we now have to really think of good treatment options in the metastatic setting, right? So I think that's where a lot of these novel combinations may come up. And what else we've seen is in a tumor agnostic trial called the DESTINY-PanTumor trial, patients who had HER2 3+ on immunohistochemistry, we saw the drug approval for T-DXd, and I think that has kind of reinvigorated the interest in HER2 in bladder cancer, because in the past targeting HER2 really didn't work. And we still don't know if HER2 is a driver or not. And at ESMO this year, we saw an excellent study coming out of China with DV which is targeting HER2, and toripalimab, which is a Chinese checkpoint inhibitor, showing pretty much similar results to what we saw with EV-pembro. Now, you know, not to do cross-trial comparisons, but that was really an amazing, amazing study. It was in the presidential session. And I think the big question is: does that really tell us that HER2-low patients will not benefit? Because that included 1+, 2+, 3+. So that part we really don't know, and I think we want to study from the EV-302 how the HER2 positive patients did with EV and pembro. So that's an additional option, at least in China, and hopefully if it gets approved here, there is a trial going on with DV and pembro. And lastly, we've seen a very promising biomarker, like ctDNA, for the first time in bladder cancer in the adjuvant setting guiding treatment with adjuvant atezolizumab. So patients who were ctDNA positive derived overall survival and recurrence-free survival benefit. So that could help us select moving forward with more studies. We can spare unnecessary checkpoint inhibitors in patients who are not going to benefit. So I think there is a lot happening in our field, and this will help do more studies because we already have the next generation FGFR inhibitors which don't have the toxicities that erdafitinib comes with. And combining those with these novel ADCs and checkpoint inhibitors, you know, using maybe TMB as a biomarker, because we really need to move away from PD-L1 in bladder cancer. It's shown no utility whatsoever, but TMB has. Dr. Rafeh Naqash: Well, thank you so much, Shilpa, for that tour de force of how things have changed in bladder cancer. There used to be a time when lung and melanoma used to lead this space in terms of the number of approvals, the biomarker development. It looks like bladder cancer is shifting the trend at this stage. So definitely exciting to see all the new changes that are coming up. I'd like to spend another minute and a half on your career. You've obviously been a leader and example for many people in the GU space and beyond. Could you, for the sake of our early career especially, the trainees and other listeners, describe how you focused on things that you're currently leading as a leader, and how you shaped your career trajectory over the last 10 years? Dr. Shilpa Gupta: That's a really important question, Rafeh, and you and I have had these discussions before, you know, being an IMG on visas like you, and being in different places. I think I try to make the most of it, you know, instead of focusing on the setbacks or the negative things. Like tried to grab the opportunities that came along. When I was at Moffitt, got to get involved with the Phase 1 trial of pembrolizumab in different tumor types. And just keeping my options open, you know, getting into the bladder cancer at that time when I wanted to really do only prostate, but it was a good idea for me to keep my options open and got all these opportunities that I made use of. I think an important thing is to, like you said, you know, have a focus. So I am trying to focus more on biomarkers that, you know, we know that 70% patients will respond to EV-pembro, right? But what about the remaining 30%? Like, so I'm really trying to understand what determines hyperprogressors with such effective regimens who we really struggle with in the clinic. They really don't do well with anything we give them after that. So we are doing some work with that and also trying to focus on PROs and kind of patient-reported outcomes. And a special interest that I've now developed and working on it is young-onset bladder cancer. You know, the colorectal cancer world has made a lot of progress and we are really far behind. And bladder cancer has historically been a disease of the elderly, which is not the case anymore. We are seeing patients in their 30s and 40s. So we launched this young-onset bladder cancer initiative at a Bladder Cancer Advocacy Network meeting and now looking at more deep dive and creating a working group around that. But yeah, you know, I would say that my philosophy has been to just take the best out of the situation I'm in, no matter where I am. And it has just helped shape my career where I am, despite everything. Dr. Rafeh Naqash: Well, thank you again. It is always a pleasure to learn from your experiences and things that you have helped lead. Appreciate all your insights, and thank you for publishing with JCO PO. Hopefully we will see more of your biomarker work being published and perhaps bring you for another podcast in a couple of years. Dr. Shilpa Gupta: Yeah, thank you, Rafeh, for the opportunity. And thanks to JCO PO for making these podcasts for our readers. So thanks a lot. Dr. Rafeh Naqash: 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. DISCLOSURES Dr. Shilpa Gupta Stock and Other Ownership Interests: Company: BioNTech SE,  Nektar Consulting or Advisory Role: Company: Gilead Sciences, Pfizer, Merck, Foundation Medicine, Bristol-Myers Squibb/Medarex, Natera, Astellas Pharma, AstraZeneca, Novartis, Johnson & Johnson/Janssen Research Funding: Recipient: Your Institution Company: Bristol Myers Squibb Foundation, Merck, Roche/Genentech, EMD Serono, Exelixis, Novartis, Tyra Biosciences, Pfizer, Convergent Therapeutics, Acrivon Therapeutics, Flare Therapeutics, Amgen Travel, Accommodations, Expenses: Company: Pfizer, Astellas Pharma, Merck    

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a series of significant updates that are shaping the future of healthcare, patient care, and drug development.The U.S. Food and Drug Administration has been particularly active recently, granting Johnson & Johnson a National Priority Review Voucher for its multiple myeloma drug combination. This move highlights the importance of J&J's treatment in addressing unmet needs within oncology, a field continuously striving for innovative solutions. These vouchers expedite the review process, reflecting a broader commitment to accelerating the availability of critical therapies for patients who need them most.Continuing with regulatory advancements, AstraZeneca and Daiichi Sankyo's Enhertu, in combination with Roche's Perjeta, has gained FDA approval as a first-line treatment for unresectable or metastatic HER2-positive breast cancer. This breakthrough is supported by late-stage study results demonstrating a 44% reduction in disease progression or death compared to standard care. The approval signifies not only progress in breast cancer therapeutics but also underscores the potential benefits of strategic collaborations in drug development. Such partnerships are increasingly vital as they aim to optimize therapeutic efficacy through shared expertise and resources.In contrast to these advancements, Pfizer is facing financial recalibrations with projected revenues for 2026 estimated to decline due to diminishing COVID-19 vaccine sales and patent expirations. This situation reflects broader industry challenges as companies navigate post-pandemic market dynamics and patent cliffs, forcing reevaluations of long-term strategies.On another front, Gilead Sciences continues to push boundaries in HIV treatment with a promising single-tablet regimen combining bictegravir and lenacapavir. This innovation targets underserved segments within the HIV market, offering streamlined treatment options that could enhance patient adherence and outcomes significantly.Shifting focus to obesity management, Novo Nordisk's oral semaglutide is emerging as a highly anticipated medication among primary care providers. This trend highlights a growing preference for oral GLP-1 therapies as convenient alternatives to injectable formulations, marking a shift in how obesity—a major public health concern—is managed.The importance of regulatory compliance remains evident as Novo Nordisk received an FDA warning letter concerning manufacturing issues at an Indiana site previously owned by Catalent. This incident underscores the necessity for rigorous quality control in pharmaceutical manufacturing, which can have far-reaching implications on operational dynamics and supply chains.The FDA is also pioneering efforts to incorporate real-world evidence into medical device submissions by opening pathways for extensive deidentified datasets from sources like national cancer registries and electronic health records. This policy shift aims to integrate diverse data sources into the evidentiary foundation for medical device evaluations, potentially fostering innovation within this sector.In line with collaborative efforts, Genentech has partnered with Caris Life Sciences in a multi-year agreement valued at up to $1.1 billion, emphasizing the strategic importance of integrating diagnostic advancements with therapeutic developments to achieve precision medicine goals.Meanwhile, Yarrow Bioscience has acquired an autoimmune thyroid disease drug from China's Gensci, exemplifying a growing trend of cross-border collaborations aimed at leveraging global innovation ecosystems to address diverse therapeutic areas. This acquisition is part of a $1.37 billion deal, reinforcing the globalization of biotech partnerships as companies seek access to novel therapeutics andSupport the show

Drs. Drago and Traina explore the evolving landscape of managing central nervous system (CNS) metastases in HER2+ breast cancer, highlighting recent advances and clinical results in targeted therapies, including neratinib, tucatinib, and trastuzumab deruxtecan, that offer new hope for patients with brain metastases.

Welcome to the Oncology Brothers podcast! In this episode, we were joined by Dr. Rutika Mehta, a GI medical oncologist from Weill Cornell. Together, we dived into the current treatment landscape for advanced metastatic gastroesophageal junction (GEJ) and gastrointestinal carcinoma, with a special focus on HER2-positive disease. Episode Highlights: • Overview of recent advancements in the treatment of resectable disease, including the approval of Durvalumab in perioperative settings. • Discussion on the importance of biomarker testing, including HER2, PD-L1, MMR, and Claudin 18.2, in determining treatment options. • Insights into frontline treatment strategies for HER2-positive patients, including the role of trastuzumab and the addition of pembrolizumab based on PD-L1 status. • The significance of retesting HER2 expression upon disease progression and the implications for treatment decisions. • Exploration of emerging therapies like TDXd and Zanidatamab, and their potential impact on the treatment landscape. • Considerations for managing side effects and the importance of treatment sequencing in palliative care. Join us for an informative discussion that aims to keep community oncologists up to date in this ever-evolving field of cancer treatment. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for more episodes covering treatment algorithms, FDA approvals, and conference highlights! Accreditation/Credit Designation Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians' Education Resource®, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Acknowledgment of Commercial Support This activity is supported by an educational grant from Jazz Pharmaceuticals, Inc. Link to gain CME credits from this activity: https://www.gotoper.com/courses/biomarker-testing-in-her2-gea-diagnosis-and-treatment-implications    #HER2GastricCancer #GastricCancer #BiomarkerTesting #OncologyBrothers #GIOncology #CME

Featuring perspectives from Dr Manish A Shah, moderated by Dr Stephen "Fred" Divers, including the following topics:  Highlights and Principles of Management of Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma — Dr Shah (0:00) Case: A man in his early 50s with microsatellite instability-high localized esophageal adenocarcinoma — Dr Mulherin (15:24) Case: A woman in her late 60s with HER2-positive (IHC 3+) and HER2 TKD-mutant metastatic esophageal adenocarcinoma — Dr Warsch (25:34) Case: A woman in her early 70s with HER2-positive (IHC 3+), PD-L1-negative, CLDN18.2-negative metastatic gastric cancer — Dr Mulherin (28:15) Case: A woman in her early 70s with metastatic gastroesophageal junction adenocarcinoma (PD-L1 CPS 15) who begins treatment with FOLFOX/nivolumab and subsequently is found to have CLDN18.2 overexpression — Dr Lamar (35:23) Case: A man in his mid 40s with CLDN18.2-positive metastatic esophageal adenocarcinoma (PD-L1 10%) who receives mFOLFOX6 and zolbetuximab — Dr Yannucci (42:54) CE information and select publications

"I'll go back to the backpack analogy. When your kids come home with a backpack, all of a sudden their homework is not on the desk where it's supposed to be. It's in the kitchen; it kind of spreads all over the place, but it's still in the house. When we give antibody–drug conjugates (ADCs), the chemotherapy does go in, but then it can kind of permeate out of the cell membrane and something right next to it—another cancer cell that might not look exactly like the cancer cell that the chemotherapy was delivered into—is affected and the chemotherapy goes over to that cancer cell and kills it," ONS member Marisha Pasteris, OCN®, office practice nurse in the breast medicine service at Memorial Sloan Kettering Cancer Center in New York, NY, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about ADCs in metastatic breast cancer. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  This podcast is sponsored by Gilead and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications.  Episode Notes  This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 391: Pharmacology 101: Antibody–Drug Conjugates Episode 378: Considerations for Adolescent and Young Adult Patients With Metastatic Breast Cancer Episode 368: Best Practices for Challenging Patient Conversations in Metastatic Breast Cancer Episode 350: Breast Cancer Treatment Considerations for Nurses Episode 303: Cancer Symptom Management Basics: Ocular Toxicities ONS Voice articles: An Oncology Nurse's Guide to Cancer-Related Ocular Toxicities Black Patients With Metastatic Breast Cancer Are Less Informed About Their Clinical Trial Options Communication Case Study: Talking to Patients About Progressive Metastatic Breast Cancer What Is HER2-Low Breast Cancer? ONS Voice drug reference sheets: Belantamab mafodotin-blmf Datopotamab deruxtecan-dlnk Enfortumab vedotin-ejfv Fam-trastuzumab deruxtecan-nxki ONS books: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) Guide to Breast Care for Oncology Nurses Guide to Cancer Immunotherapy (second edition) ONS courses: ONS Fundamentals of Chemotherapy and Immunotherapy Administration™ ONS/ONCC® Chemotherapy Immunotherapy Certificate™ Clinical Journal of Oncology Nursing article: Antibody–Drug Conjugates and Ocular Toxicity: Nursing, Patient, and Organizational Implications for Care The Association Between Hormone Receptor Status and End-of-Life Care Among Patients With Metastatic Breast Cancer Oncology Nursing Forum article: Impact of Race and Area Deprivation on Triple-Negative Metastatic Breast Cancer Outcomes ONS huddle cards: Altered Body Image Huddle Card Chemotherapy Huddle Card Targeted Therapy Huddle Card Foundations of Antibody–Drug Conjugate Use in Metastatic Breast Cancer: A Case Study ONS Biomarker Database (refine by breast cancer) ONS Breast Cancer Learning Library American Society of Clinical Oncology (ASCO) homepage Drugs@FDA package inserts National Comprehensive Cancer Network homepage Susan G. Komen metastatic breast cancer page To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS 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 "What an ADC is doing is taking the antibody and linking it to a cytotoxic chemotherapy with the idea of delivering it directly into the cell. How I explain this to new nurses or patients is a backpack analogy. If we think of it as a HER2 molecule wearing a chemo backpack, it's going to find the HER2 receptor attached to it and then drop the chemotherapy into the cell via the backpack. Similar to how we come home from work, we open the key to our door, we're carrying all of our items, and then we drop our own personal items in our house." TS 2:30 "The reason that so many patients with metastatic breast cancer are able to receive ADC therapy is because they are targeting two very common antibodies that we see in breast cancer. One is HER2 and the other is trophoblast cell surface antigen 2 (TROP2). These are seen across the board. We see these on triple-negative breast cancers, hormone receptor–positive cancers, and HER2-positive breast cancers. And now we have a new way to talk about HER2, which is a HER2-low. ... Recently, we have found that patients who express low levels of HER2 are able to receive ADC therapy, specifically fam-trastuzumab deruxtecan." TS 4:21 "Another [ADC] that has just been approved is datopotamab deruxtecan. This is another ADC that targets the TROP2 receptor on a cancer cell. This one carries a lot of side effects. I mentioned earlier that you need an ophthalmology clearance because there is a lot of ocular toxicity around this one. We see a lot of blepharitis, conjunctivitis, there can be blurred vision. Another thing we monitor on this one is mucositis. In the package insert, there's a recommendation for using ice chips while receiving the treatment. ... Then in the HER2-positive and HER2-low space is the big one, which is fam-trastuzumab deruxtecan. This was approved in 2019 for the HER2-positive patients, then more recently in the HER2-low [patients]. The big [side effect] with this one is interstitial lung disease." TS 10:11 "Interstitial lung disease is an inflammation or a little bit of fibrosis within the lung that causes an impaired exchange between the oxygen and carbon dioxide. This was seen in the clinical trials, specifically around fam-trastuzumab deruxtecan. During the trials, they had a very small percentage, I think it was 1%, that died due to interstitial lung disease. So, this is a very important side effect for us as nurses to be aware of. It typically presents in patients like a dyspnea. A lot of times, it's like, 'Well, I used to be able to walk my kid to the bus stop, but now when I walk there, I feel really short of breath.' Or 'I've had this dry cough for the past couple weeks and I've tried medications, but haven't had that relieved.' So, we really need to be aware of that because early intervention in interstitial lung disease is key." TS 12:57 "ADCs are toxic drugs. They have the benefit of being targeted, but we know that they carry a lot of side effects. ... Their specificity makes them so wonderful and we've seen amazing responses to these drugs. But also, we want patients to be safe. We want to give these drugs safely. So, we have to assess our patients and make sure that this is an appropriate patient to give this therapy to. I think that's an open conversation that clinicians need to have with patients regarding these drugs." TS 18:08

Featuring perspectives from Dr Justin F Gainor, Dr Corey J Langer and Dr Misty Dawn Shields, moderated by Dr Stephen "Fred" Divers, including the following topics:  Introduction (0:00) Targeted Therapy for Non-Small Cell Lung Cancer (NSCLC) — Dr Gainor, MD (5:32) Case: A woman in her mid 60s with ALK-mutant metastatic adenocarcinoma of the lung (PD-L1 TPS 70%) — Zanetta S Lamar, MD (17:59) Case: A woman in her mid 80s with EGFR exon 19-deleted adenocarcinoma of the lung with recurrence after 4 years of osimertinib — Jennifer Yannucci, MD (27:53) Case: A woman in her late 60s with HER2-mutant metastatic adenocarcinoma of the lung — Brian P Mulherin, MD (39:41) Case: A man in his early 70s with locally recurrent squamous cell carcinoma of the lung and a MET exon 14 skipping mutation — Sean Warsch, MD (46:39) Case: A woman in her early 70s with ROS1-mutant metastatic adenocarcinoma of the lung that responds to entrectinib and then to pembrolizumab/carboplatin/pemetrexed administered upon disease progression — Dr Yannucci (52:44) Nontargeted Therapy for NSCLC; Small Cell Lung Cancer — Dr Langer (58:16) Neoadjuvant, Perioperative and Adjuvant Anti-PD-1/PD-L1 Antibody-Based Approaches for Patients with Localized NSCLC — Dr Shields (1:14:14) Case: A man in his mid 60s with localized adenocarcinoma of the lung who receives neoadjuvant cisplatin/pemetrexed/pembrolizumab and achieves a pathologic complete response — Dr Mulherin (1:23:19) Case: A man in his early 60s with metastatic mixed adenosquamous NSCLC (PD-L1 TPS 50%) — Sunil Babu, MD (1:30:04) Case: A man in his late 50s diagnosed with extensive-stage small cell lung cancer who receives carboplatin/etoposide/durvalumab — Dr Warsch (1:34:07) CE information and select publications

Dr. Drago and Dr. Traina continue their discussion of breakthrough developments in triple-negative breast cancer treatment, sharing highlights from the promising ASCENT-04 trial results with sacituzumab govitecan plus pembrolizumab in first-line treatment. They also address key clinical challenges around sequencing antibody-drug conjugates and managing interstitial lung disease toxicity.

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. In this episode, Dr Matulonis sat down with guest Panagiotis (Panos) A. Konstantinopoulos, MD, PhD, to discuss the different subtypes of endometrial cancer and treatment developments for this disease. Dr Konstantinopoulos is the director of Translational Research in the Division of Gynecologic Oncology, the director of the Mellen and Eisenson Family Center for BRCA and Related Genes, and the Velma Eisenson Chair for Clinical and Translational Research at Dana-Farber Cancer Institute; as well as a professor of medicine at Harvard Medical School. Drs Matulonis and Konstantinopoulos explained that patients with mismatch repair–deficient (dMMR) tumors substantially benefit from a decreased risk of progression or death when immunotherapy is added to standard therapy. They noted that immunotherapy appears important for the management of dMMR tumors, even those in earlier stages or in patients who have no measurable disease remaining after surgery. For MMR-proficient (pMMR) tumors, Drs Matulonis and Konstantinopoulos highlighted that PD-1 blockade combined with chemotherapy improves survival vs chemotherapy alone, but that this benefit is not as substantial as that seen in dMMR disease. Crucially, they reported that if a pMMR tumor has no measurable disease after surgery, adding immune checkpoint blockade does not appear beneficial. They stated that tailored treatment approaches are key for managing pMMR disease subtypes. They added that hormonal therapy may be used upfront for slow-growing, estrogen receptor–positive metastatic disease. They continued by saying that DNA damage and replication stress are critical targets, particularly in p53-mutated tumors, like uterine serous cancers. Furthermore, they stressed that although the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) is highly effective in HER2-positive tumors, treatment with this agent requires monitoring for toxicities, including interstitial lung disease and decreased ejection fraction.

Dr. Alison Loren and Dr. Ann Partridge share the latest guideline from ASCO on the management of cancer during pregnancy. They highlight the importance of this multidisciplinary, evidence-based guideline and overarching principles for the management of cancer during pregnancy. Drs. Loren and Partridge discuss key recommendations from each section of the guideline, including diagnostic evaluation, oncologic management, obstetrical management, and psychological and social support. They also touch on the importance of this guideline and accompanying tools for clinicians and how this serves as a framework for pregnant patients with cancer. The conversation wraps up with a discussion on the unanswered questions and how future evidence will inform guideline updates.  Read the full guideline, "Management of Cancer During Pregnancy: ASCO Guideline" at www.asco.org/survivorship-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/survivorship-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-02115   Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Alison Loren from the Perelman School of Medicine of the University of Pennsylvania and Dr. Ann Partridge from Dana-Farber Cancer Institute, co-chairs on "Management of Cancer During Pregnancy: ASCO Guideline." Thank you for being here today, Dr. Loren and Dr. Partridge. Dr. Alison Loren: Thanks for having us. Dr. Ann Partridge: It's a pleasure. Brittany Harvey: And then just before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Partridge and Dr. Loren who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into the meat of this guideline, to start us off, Dr. Loren, could you provide an overview of the scope and purpose of this new guideline on the optimal management of cancer during pregnancy? Dr. Alison Loren: Sure, thanks, Brittany. So this was really born out of I think a lot of passion and concern for this really vulnerable patient population. We have observed, and I am sure it is not any surprise to your audience, that the incidence of cancer in young people is increasing. And simultaneously, people are choosing to become pregnant at older ages, and so we are seeing more and more people with a cancer diagnosis during their pregnancy. And for probably obvious reasons, there is really no way to do randomized clinical trials in this population. And so really trying to assemble and articulate the best evidence for safely managing the diagnosis of cancer, the management of cancer once it is confirmed, being thoughtful about obviously the health of the mom, but also attending to potential risks to the developing fetus, and really just trying to be really comprehensive and balanced about all the choices for these patients when they are facing some really challenging decisions in a very emotionally fraught environment. And I think it is really emotionally fraught for the providers, too. You know, this is obviously an extremely intense, very emotional set of decisions, and so trying to provide a rudder essentially to sort of help people frame the questions and trying to make as evidence-based a set of recommendations as possible. Dr. Ann Partridge: And I would just add that "evidence-based" is a strong word here because typically our, as you just heard, our gold standard evidence is a randomized trial, but you can't do that in this setting, in general. And so, what we were able to do with the support of the phenomenal ASCO staff was to pull together kind of the world's literature on the safety and outcomes of treatments during pregnancy, as well as consensus opinion. And I think that is a really, really critical difference about this particular guideline compared to many of the other ones that ASCO does, where consensus and good judgment needed to kind of rule the day when evidence is not available. So, there is a lot of that in our recommendations. Dr. Alison Loren: That is such a good point. And I just, before we move forward, I just want to reflect that the composition of the panel was really broad and wide-ranging. We had maternal medicine specialists, we had legal and ethical experts, we had representatives who understand pharmaceutical industries' perspectives, and then medical oncologists representing the full spectrum of oncology diagnoses. And so it was a really diverse, in terms of expertise, panel, internationally composed to try to really get the best consensus that we could in the absence of gold standard evidence. Brittany Harvey: Absolutely. That multidisciplinary panel is really key to developing this guideline and, as you said, looking at the evidence and even though it does not reach the level of randomized trials, still critically evaluating it and reviewing that along with consensus to come up with optimal management for diagnosis and management of cancer during pregnancy. So then to follow that up, I would like to next review the key recommendations of the guideline across the main sections that the expert panel provided. First, I will throw this out to either of you, but what are the important general principles for the management of cancer during pregnancy? Dr. Ann Partridge: I think there were three major principles that we hammer home in the guidelines. One is that this is a team sport. It is multidisciplinary care that is necessary in order to optimize outcomes for the patient and potentially for the fetus. And that you really need to, from the beginning, bring in a coordinated team, including not just oncologists but obstetricians, maternal-fetal medicine specialists, neonatologists, ethics consultants, and obviously the patient and potentially her family. So that, I think, is one of the most important things. Second would be that obviously in a pregnancy, there are two potential patients and that the nuances of safety and risk from treatment is really wrapped up in where in the trimester of the pregnancy the patient is diagnosed, along with the kind of cancer that it is, both the urgency of treatment and the risk of the cancer, as well as the potential risks of any given intervention across the cancer continuum. It is a broad guideline in that regard. And then finally, and this is particularly timely given what is going on from a sociopolitical standpoint in the U.S., really thinking about informed consent and potential ethical as well as legal implications of some of the choices that patients might have when they are thinking about, in particular, continuing a pregnancy or potential termination. Dr. Alison Loren: And I will just add that I think that the key to all of this guidance is nuance and individualization and also making sure that patients and their care providers understand all the choices that are available to them and also the consequences of those choices. You know, nobody would choose to receive chemotherapy during pregnancy if that wasn't necessary. So there are risks to treatment, but there are also risks to not treatment. And making sure that in a suboptimal situation where you do not have a lot of evidence, trying to weigh, the best you can, the risks and benefits of all of the choices so that the patient can come to a decision about the treatment plan that is right for her. Brittany Harvey: Definitely. And those core concepts really set the stage for individualized care on what is necessary for appropriate multidisciplinary care, prioritizing both patient autonomy and informed decision making. With those core concepts and key principles in mind, I would like to move into the recommendations section of the guideline. So what are the key recommendations regarding diagnostic evaluation for pregnant patients with signs or symptoms of cancer? Dr. Alison Loren: I think the most important thing is to not delay, that there are very careful and well-thought-out recommendations for how to evaluate a potential cancer. And while there are certain things that we know can be harmful, particularly when certain dose thresholds are exceeded - for instance, abdominal imaging, there are certain radiographic thresholds that you don't want to exceed because of risk of harm to the embryo or fetus - there are still lots of options for diagnosing cancer during pregnancy. And again, thinking about the costs of not doing versus the cost of doing, right? It is really important to make the diagnosis of cancer if that is a consideration or a concern. And sometimes going directly to biopsies or getting definitive studies, even if there is a small risk to the developing fetus, is really essential because if the mom does not survive, of course, the fetus is also not going to survive. And so we need to be thinking first about the patient who is sitting in front of us, the woman who needs to know what is going on in her body so she can make good decisions about her health. So, I think that is a key principle in thinking about this. Brittany Harvey: Absolutely. So, following that diagnosis of a new or recurrent cancer, what is recommended for oncologic management of patients who are diagnosed with cancer during their pregnancy? Dr. Ann Partridge: So, I think the general principle is, again, cancer is such a wide number of diseases and even within diseases, a range of stages and risks and associated opportunities for risk reduction and/or treatment depending on the type of cancer. Just by example, in the work that I do, which is breast cancer, once someone has had a surgery in the early-stage setting, a lot of our treatment is about risk reduction. And that is very different than from what Alison does, which is treating people with leukemia, where it is kind of binary. If you do not treat, including with cytotoxic drugs, the patient and an unborn fetus will die, especially early in the pregnancy, obviously. So this is where cancers are very, very different. So I think taking the approach of what would you do if the patient were not pregnant? And what is the best treatment for that particular patient with that particular kind of cancer? And then applying the pregnancy and where the patient is in that pregnancy in terms of the trimester of the pregnancy, and what is safe and what is unsafe from the options that you would give her if she were not pregnant. And then if the patient is choosing to keep the pregnancy, which in my practice, many people come and they come to me because they want to hold onto their pregnancy and want to figure out how to make it work, coming up with a regimen that tries to give them kind of the best bang for the buck, the best possible breast cancer therapy with the least harm, when possible, to the fetus. It is a bit of a balance, right? And then we cannot always give people the best approach. And sometimes it comes down to making a decision to give up something that may improve their survival so as not to harm the fetus. And sometimes it goes the opposite direction where a patient will say, "Oh, that is going to improve my survival by 5% and you can't give it to me now? I am going to choose to terminate." Even though that is obviously a very, very difficult and challenging decision to make in this setting because they want to optimize their survival and ideally live on to potentially have another pregnancy in the future if that is something that is of interest to her. So these are really, really hard conversations as you can imagine, but that is kind of where we go. Dr. Alison Loren: Yeah, and I think this is where the need for more research and understanding is really key because sometimes questions come up. I guess I am thinking about like HER2-directed agents, which we know are contraindicated in pregnancy. But what about sequencing? Does it matter when you get it? Can you get it later? I think that is something that we don't really fully understand. And similarly, again, this is obviously like a breast cancer and blood cancer focused discussion because that is what we do, but thinking about managing blood cancers, certainly with acute lymphoblastic leukemia, there is actually a lot of options now that, you know, you could potentially use to temporize or sort of get somebody through a pregnancy relatively safely. I am focusing on the word "relatively" because we do not know what the long-term impact might be of potentially not optimal therapy in the long run. And then thinking about other things like timing of a bone marrow transplant relative to either delivery or termination. I mean, again, we really do not know what are the right sets of sort of timing considerations for those. So there are just a lot of unknowns. And I think trying to be sort of self-aware and humble and honest about those unknowns so that the patient can engage in the conversation in a way that is meaningful to her and make the decisions that make the most sense for her. I think the most important thing is to make sure that the patient feels supported and safe to make those decisions with as little regret as possible. Brittany Harvey: Yes, I think it is really important that you mentioned that there is a wide range of cancers here, and that means that care really needs to be individualized for each patient. I will also note, just in this section, that I found really informative while reading through the guideline the list of oncologic agents that may be offered in each individual trimester, whether it is contraindicated or it can be used with caution, or if there is relatively good safety data on it for prioritizing maternal treatment needs and balancing fetal safety at the same time. I think that is, that is really key. And I think readers will really like that section of the guideline to provide concrete information for them and their patients. Dr. Alison Loren: Thank you. We actually spent a lot of time on that table and just thinking about what it should look like, what the format ought to be, what the language ought to be. Because of course, at the end of the day, everything should be used with caution. So what does that actually mean? And we sort of tried to explicate that a little bit in like the footnotes. We really tried to leverage what we know from clinical experience, from package labels, from mechanism of action to try to be as clear and definitive as we could be without overstating or understating what we know. Dr. Ann Partridge: Yeah, and I think we are focusing on breast and leukemia because that is what we do. But the truth is much of the data comes from those two areas. Leukemia, not because it is so common, but because you do not really have choices to treat or not treat. And so for decades, they have been treating and saying, "We hope the progeny comes out okay." And for many agents it does. The babies are okay. And so, we have reasonable observational data. And then in breast cancer, there have been actually some prospective registry-type studies where people have been followed and treated when pregnant, and the progeny have been accounted for, and so we have some good experience in that way too. Again, not randomized trials, but at least data that suggests certain agents are safe. And increasingly, because of that, when we have had to treat patients, we have said, "Okay, let us do it on this registry so that we can at least learn from every patient that comes in in this situation." And so, I think we will have more and more data given the growing number of young adults with cancer and the delays in childbearing that are happening around the world, and particularly in Westernized countries. I wish we did not. We wish we did not see this problem, but of course, when we do, we have to make sure that we learn from it and try and get patients enrolled in these registries and any kinds of studies that are available. Dr. Alison Loren: Yeah, I will just underscore that to say that, you know, there is outcomes of pregnancy and then there is outcomes of pregnancy, right? So there is like, "Okay, the baby was born with 10 fingers and 10 toes, and they passed their Apgar, and they are doing all their developmental processes along the way." But what happens when they are 10 or 15 or 20? Are they maturing normally? Are they cognitively intact? And then, of course, it is really inseparable from what is the impact on a family of having the mom with cancer? And how does that impact childhood development and intellectual development? And so these are really, really important questions that are very difficult to answer given the longitudinal information that you need, but it is a really critical question that, you know, patients ask and we do not know the answer. Dr. Ann Partridge: Yeah, that actually leads me to one of the important principles in the guideline that is a little bit of a change from when I first started practicing, which is we have learned from the wider neonatology literature, as they have followed up on the children that were born prematurely, that it is actually better not to be premature and to keep the baby in utero as long as it is safe for the fetus and the mother as long as possible, ideally to term rather than delivering early and then giving the chemo after that or separating the chemo from before and after. We used to try and deliver early and then give agents, but now we typically will give agents that are safe to be given at the end of pregnancy, ideally close to term, a couple weeks out, to allow for the ability of count recovery, and you do not want to go into preterm labor with chemotherapy on board, but we used to go much earlier and have an argument with our maternal-fetal medicine doctors. "How early can you get them out?" And they would say, "How long can they stay in?" And increasingly, we have been able to try and compromise to go even later and allow the fetus to go to term because of the neonatal outcomes that in longer term there is a suggestion that the children are developing better in the long run if they are kept in utero for as long as possible. Dr. Alison Loren: Yeah, that is such a great point. I think that is probably the most important thing for people to take away. For anyone who sort of does this, I mean, no one does this regularly because it is a rare event, although I think it is increasing as I mentioned. But this idea that the third trimester is, most of us know, is primarily a time for growth. Most of the critical development has already occurred, and so administering most chemotherapy agents towards the end of the third trimester seems to be preferable long term than delivering them early. So that is a really big change. I think we used to try to sort of, "Oh, get them to 30 or 32 weeks and then deliver," but we really are trying to get them closer to term, 37 weeks or more, and then coordinating the treatment so that they are not nadiring, as Ann said, at the time of planned delivery. Brittany Harvey: Yes, and that is a really important point related to evidence-based care and why we have changed that practice. And so then that actually leads nicely into my next question. But as you both mentioned, this is an important collaboration between oncologists and obstetricians. So the next section of the guideline addresses obstetrical practice. And so beyond what is standard, what additional recommendations are there in obstetrical management for pregnant patients with cancer? Dr. Alison Loren: That is a great question. So I will say we were really struggling with like how much do we cover? Like this is an oncology guideline. We are not obstetricians. We certainly had great representation from our maternal-fetal medicine colleagues on the panel. But really trying to sort of give useful information without overstepping. And so I think that the main recommendations are to increase the frequency of fetal monitoring, make sure that there is close attention to blood counts in the patient. But I think there is really still a gap in terms of what we know about optimal management of a pregnant person who is receiving therapy and how to handle the pregnancy itself. The delivery should be a usual delivery. Our colleagues did not recommend a planned C-section. They recommended usual care in terms of planning for the delivery. Obviously, if a C-section is indicated, then it should be done, but it should not be planned this way because of the cancer diagnosis. And I guess the other thing that we mentioned in the guideline, although we were reluctant to push it too hard because of access to these specialized services, was evaluating the placenta after birth to ensure that there were no metastases in the placenta itself. Dr. Ann Partridge: Those are the main things, and judicious and prudent obstetrical care, as I think, you know, is trying to be practiced regularly with MFM. Typically these patients should be followed not by your average OB/GYN, but a maternal-fetal medicine specialist because these patients will have special concerns, especially if they are sick. So oftentimes, especially Alison's patients, are actually sick with leukemia. And so you are monitoring them a lot, whereas, you know, a breast cancer patient typically isn't sick, although they could get sick with their chemotherapy. And so we really want to hand-in-hand manage these patients with our MFM colleagues. Dr. Alison Loren: I think we also highlighted in the guideline just for the refresher purposes of the oncology community, generally which drugs that would be given in a normal oncology setting are safe to be given to a pregnant person. So we talked a little bit about what kinds of steroids are recommended, antiemetics, DVT prophylaxis, peripartum. These are things that we think about a lot in oncology, but just want to make sure that it sort of intersected appropriately with the care of a pregnant patient. Brittany Harvey: Definitely. That specialized care is really important for patients who are pregnant and have cancer. And then the last section of the recommendations addresses psychological and social support. As you both mentioned before, this is a highly emotional time and it can be difficult and challenging to make decisions. So what is recommended for the psychological and social support of pregnant patients with cancer? Dr. Ann Partridge: Well, as I said, it is really something that needs to be considered at the beginning, through the diagnostic period, all the way into survivorship. Ironically, even though it is a highly fraught, emotional situation, I find that my pregnant patients actually are extraordinarily resilient, and what they are really focused on often is the safety of the fetus, because again, many of the people that come to me, it is a highly wanted pregnancy. They are also focused on their own health, of course, and often you need to bring in social work, sometimes a psychologist, professionals who are there just to help manage their emotions while we are focusing on what do they need medically to be as healthy as possible, both for the again, the mother, the patient, and the fetus. It is very tricky, and I will say also bringing in sometimes people on the ethics team in the hospital to help, both from the "Are you recommending and giving something that is safe?" That is number one. And then number two, sometimes patients want to be treated with drugs that we do not have any safety data for in pregnancy. What are our obligations? I think most of us would say we would not treat someone if we do not have safety data and there is suspicion for concern. But where is that line in terms of the right thing to do by that patient? And so we are all beholden to our ethics colleagues to help us when we make decisions like that. You know, we all want to do right by the patient, but we have to uphold our oaths and legal obligations. I don't know if you have to add on that because it's very tricky. Dr. Alison Loren: It is, it is very hard. I mean, I think, you know, there is a lot of emotion, obviously any cancer diagnosis is extremely charged and people are already at sort of a heightened, you know, they are anticipating a new baby and planning around that. And so it is just an extremely disruptive is the smallest word I can think of to describe it. And I think that often there is a co-parent, there might be parents and in-laws and other siblings, and then there is care after delivery. And so it is just a very complex set of dynamics. And having both our ethics colleagues and our psychology and social work colleagues to sort of just pitch in and make sure that the patient is being supported. I think there are sometimes really difficult situations where maybe what the patient wants is different from what the father of the baby wants or what the rest of the family wants. And so that can be really challenging. And you never really know where those landmines are going to pop up. So it is good to have the team on board early and often. Dr. Ann Partridge: Yeah, I would add to that, the other thing here that I think is really important, like in all of medicine but especially in situations like this, this is where we have to be very careful as professionals not to impose our own ethical, moral, emotional, personal views on the patient and to try to reserve judgment as much as possible. We are their navigator with the most important evidence and information that we can provide in the current situation. And that is where this guideline is extraordinarily helpful, we hope, for clinicians in the years to come. And at the same time, we cannot necessarily impose our own views and what we would do on a patient or what we tell our daughters, sisters, friends, family members. It is very tricky in that way. And so sometimes not just support for the patient, but support for the care team may be warranted in some of these very fraught situations. Dr. Alison Loren: Yeah, that is such a great point. And I was sort of thinking that too. I mean, it is, of course, the patient is front and center, but these are really difficult situations to navigate. And I will just add also that a lot of times these patients end up in academic centers, which I think is that's where the expertise or even just the experience may be. But the downside of that is that, you know, the teams are constantly changing. You have a new resident, you have a new intern, you have a new attending, a new fellow. And so, you know, the patients may be subjected to lots of different ways of communicating and sometimes those perceived differences can be really challenging. So sort of team huddles to sort of make sure that everybody is reading from the same script and everyone is comfortable with how the information is being presented so that the patient does not feel more confused or more overwhelmed, that they are kind of getting a consistent message from the whole team that, "This is what we know, this is what we are recommending, here are your other choices, and here are the pros and cons of each of these options." Brittany Harvey: Yes, I think you have both touched on this and that bringing in appropriate experts to support both clinicians and patients and their decision-making and their mental health is really important for this section of the guideline. We have already discussed this a fair bit throughout our conversation, but in your view, what is the importance of this guideline and how will it impact both clinicians and pregnant patients diagnosed with cancer? Dr. Ann Partridge: I could start with that. We just talked about experts and having them all around, but the fact is most people do not have the experts all around when they are dealing with this. And I think this is, you know, an expert-based, evidence-based guideline where having this in one's back pocket, whether you are in rural Montana or at a major cancer center on either coast, you will be armed with the latest and the greatest in terms of what we know and what we do not know, and some very helpful algorithms for how to think through the process of dealing with a patient who is diagnosed during pregnancy, whichever type of cancer it is. We could not cover every single specific thing about every cancer, although it is a pretty long guideline and there is a lot of nuance in there. So you might find a lot about specific cancers. And I think that that will be very, very helpful for people who are faced with this situation in the clinics just to frame it out, think through. Sometimes there is no answer that is the perfect answer and then, you know, using this as kind of a scaffolding and phoning a friend who may have more experience to help guide you and guide the patient, most importantly. I think it will be very helpful in that regard. Dr. Alison Loren: Yeah, I think so too. And I have talked about that we are working on this guideline and the anecdotal feedback has been, "This is so helpful." Like there really has not been, I think, an all-in-one place, diagnostic considerations, radiographic considerations, staging, treatment, all the modalities, surgical, radiation, systemic chemotherapy. We tried to include, when we could, novel agents including targeted agents and monoclonal antibodies and bispecifics and cellular immunotherapies and non-cellular immunotherapies. We really, really tried to cover in 2025 what are people using to treat cancer and to try to give the most balanced view of what we think is is safe or reasonably safe and what we think is either unproven or known to be risky, really to have it be kind of a go-to, like all-in-one, as much information as we have about these really challenging cases. We tried to include, Ann mentioned, you know, specific cancers, and I think when there were specific things to shout out with specific cancers, we really tried to highlight that. Like, "Okay, lots of young patients with cancer have Hodgkin's lymphoma, so what is safe and what is not for that specific case?" Or, "What is safe or what is not when you are thinking about colon cancers?" And we have a shout-out in here about considering checking for DPD deficiencies in patients who are pregnant. And I know it is generally recommended nowadays, but certainly for people who are pregnant, you know, you really want to avoid excess toxicity. So I think just really trying to be attentive to specifics about certain cancers in young patients and what would be valuable for a practicing oncologist and obstetrician to know when you are faced with this situation. Dr. Ann Partridge: Yeah, and I think the other critical thing that is great about this guideline is it's a starting place. And I anticipate that we will be building on this guideline for many years to come. And remember that when first, I was not around then, but probably three or four decades ago, when chemotherapy was just coming out and patients were coming in pregnant, there was a feeling I am sure that was, "We cannot give this to this person because it is purposefully going to destroy cells. And when you destroy cells in a growing fetus, you are going to destroy or harm that fetus." And yet, people did not have great choices. It was get treated or die, especially with things like leukemia early on. And bold patients along with their oncologist said, "Bring it on." And that is how some of this literature has been born. And so moving forward, there will be either purposeful exposures or inadvertent exposures of some of our therapies where we will learn ultimately. And this is a place where we can update these guidelines. That is the beautiful thing about the ASCO guidelines is that they are constantly being thought about to be updated. And then when there is enough of a change in practice, they will be updated such that they will continue to inform how we do this in the years to come for patients who come in pregnant. Dr. Allison Loren: Yeah, and I will say I have been doing this long enough now, we were just talking about a different guideline, the fertility guideline earlier today, and over the 20 years that the fertility guidelines have been out, just the amount of research has really skyrocketed. And you can see as you look at each guideline how much we have learned, what we can say, "Yes, this is working," "No, this is not working." Like, it is stuff that we used to say, "Oh, we do not really know," and now we have answers.  I think I speak for both of us when I say that we are hopeful that this will serve as, as Ann said, as a starting off point and really inspire people to ask the questions and do the research so that we can give better guidance moving forward, really trying to think about, you know, mechanisms and leaning on our colleagues in pharma and in the government who sort of think about safety and efficacy, to sort of make sure that they are contemplating not just non-pregnant patients, but also pregnant patients or as they are thinking about marking the package inserts with safety guidelines around this. Brittany Harvey: Yes, this is a critically important first guideline on the management of cancer during pregnancy, and we will look forward to continuing to build on that. I think as you mentioned, this guideline is far-reaching and has a lot of recommendations in it. And so both the full text of the guideline and those at-a-glance algorithms, figures, and tables will be really useful for clinicians in their clinic. Finally, to wrap us up, we have just been discussing this a little bit, but specifically, what are the outstanding questions on the management of pregnant patients with cancer, and where is this further research needed? Dr. Alison Loren: There are lots and lots and lots of unanswered questions. And I think if you look at the table, most of what we say is, "We are pretty sure this is okay, we are not so sure about this." I am paraphrasing, but we really just are operating in a paucity of what we would normally consider gold-standard evidence. It is hard to imagine, of course, there would ever be, as we mentioned in the beginning, randomized trials. But I think that preclinical data, mechanistic data, trying to think about including as we go through animal data, making sure that we are looking at female animals and pregnant animals so that we can sort of fully understand what the impact may be. And then I think thinking about more localized therapies around sort of radiation, you know, we are now moving into really hyper-focused radiation treatments like protons. Is that better because there is less scatter? Like I think those are real considerations that we just do not know the answer to. What do you think? Dr. Ann Partridge: I think so many unanswered questions, and this is a call to action to continue to and increase the documentation of the experiences and outcomes for patients diagnosed during pregnancy. Dr. Alison Loren: Yeah, and I think the long-term outcomes too are really going to be critical. Brittany Harvey: Yes, we will look forward to learning about more evidence across the spectrum of care to inform future updates to this guideline. So I want to thank you both so much for your work to develop this guideline, to review the extensive amounts of literature that you did, and work to create this guideline. And thank you also for your time today, Dr. Loren and Dr. Partridge. Dr. Alison Loren: Thanks. It was fun. Dr. Ann Partridge: Yeah, thank you. Brittany Harvey: And finally, thank you to all of our listeners for tuning into the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/survivorship-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 

This week, we look at new studies on high-dose influenza vaccines for older adults, antiplatelet therapy after coronary surgery, and HER2-targeted immunotherapy for advanced bladder cancer. We review complex regional pain syndrome and a pediatric case of fever and rash. We also explore FDA innovation and safety, aspirin's role in metastasis prevention, the meaning of “the good doctor,” smallpox in the Revolution, and how AI may reshape medical science.

Featuring an interview with Dr John V Heymach, including the following topics: Differentiating factors among various HER2 alterations in non-small cell lung cancer (NSCLC) (0:00) Activity of targeted agents across HER2 alterations in NSCLC (4:06) Available data with zongertinib and sevabertinib for HER2-mutant NSCLC (20:39) Case: A man in his late 40s with HER2-mutant NSCLC receives multiple lines of therapy, including trastuzumab deruxtecan (T-DXd) and zongertinib (29:23) Case: A woman in her mid 50s with HER2-mutant NSCLC receives zongertinib with durable response (34:23) Case: A woman in her late 50s with HER2-mutant NSCLC receives multiple lines of therapy, including sevabertinib and T-DXd (39:53) Investigational approaches in HER2-mutant NSCLC (46:31) CME information and select publications

Dr. Tiffany Traina and Dr. Josh Drago discuss the evolving treatment landscape for HER2-low and ultralow breast cancer, highlighting how pivotal trials like Destiny Breast-04 and Destiny Breast-06 have demonstrated significant efficacy improvements with trastuzumab deruxtecan while emphasizing the need to balance its toxicity profile with benefits for individual patients.

Featuring a slide presentation and related discussion from Dr John V Heymach, including the following topics: Overview of the biology and treatment landscape of HER2-mutant non-small cell lung cancer (NSCLC) (0:00) Datasets evaluating trastuzumab deruxtecan for HER2-mutant NSCLC (5:03) Clinical data with zongertinib for HER2-mutant NSCLC (6:35) Emerging data with sevabertinib for HER2-mutant NSCLC (14:41) Other investigational strategies being evaluated for HER2-mutant NSCLC (19:10) Summary of the current and future treatment landscape of HER2-mutant NSCLC (21:52) CME information and select publications

Featuring an interview with Dr Priyanka Sharma, including the following topics: Endocrine therapy for hormone receptor-positive, HER2-negative high-risk localized breast cancer (0:00) Johnston SR et al. monarchE: Primary overall survival (OS) results of adjuvant abemaciclib + endocrine therapy (ET) for HR+, HER2-, high-risk early breast cancer (EBC). ESMO 2025;Abstract LBA13. Durvalumab in combination with neoadjuvant chemotherapy for localized triple-negative breast cancer (TNBC) (3:25) Loibl S et al. Durvalumab in combination with neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC) – Long-term analysis from the GeparNuevo trial. ESMO 2025;Abstract 292MO.  Efficacy and safety findings with TROP2-directed antibody-drug conjugates for metastatic TNBC (5:11) Cortés JC et al. Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i). ESMO 2025;Abstract LBA20.  de Azambuja E et al. Patient-reported outcomes (PROs) with sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in patients (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC) in the phase III ASCENT-04/KEYNOTE-D19 study. ESMO 2025;Abstract LBA22.  Dent R et al. First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase III TROPION-Breast02 trial. ESMO 2025;Abstract LBA21.  CME information and select publications

We are back with lots of OncoPharm updates: 1. The belantamab mafodotin REMS program details are available....and it's a lot. How will belantamab mafodin-regimens be used with the upcoming MAJESTIC-3 data of teclistamab-daratumumab? 2. The capecitabine label is updated and calls for pre-treatment DPYD testing 3. Daratumumab gets an FDA approval for high-risk smoldering myeloma based on the AQUILA study Critique of AQUILA: https://doi.org/10.1093/oncolo/oyaf216 4. A pertuzumab biosimilar (Poherdy) is approved 5. Epcoritamab nets regular approval and a new indication with lenalidomide/rituximab (RR) for Follicular Lymphoma 6. Ziftomenib, a new menin inhibitor, is approved for NPM1 relapsed/refractory AML 7. Sevabertinib, a new HER2 inhibiting TKI, is approved for ERBB2 mutated NSCLC, with evidence of activity in patients previously treated with HER2-antibody-drug conjugates 8. Expected FDA approvals for durvalumab + FLOT in preoperative gastric/GEJ cancer; neoadjuvant pembrolizumb + enforumab vedotin in bladder cancer (non-cisplatin eligible), and tarlatamab regular approval for small cell lung cancer 9. Happy Thanksgiving!