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This week's episode will be focusing on an ASCO 2026 Plenary abstract, SARC 041. SARC041 is the first positive phase 3 randomized controlled trial of a CDK4/6 inhibitor in advanced dedifferentiated liposarcoma (DDLPS), demonstrating that abemaciclib significantly improves progression-free survival compared to placebo.
Featuring perspectives from Dr Sara A Hurvitz and Dr Virginia Kaklamani, including the following topics: Introduction: Which Biomarkers and When (0:00) Optimizing First-Line Therapy for Patients with Hormone Receptor (HR)-Positive Metastatic Breast Cancer (mBC) (5:31) SERENA-6 Trial (19:44) Inavolisib (23:08) Management of HR-Positive mBC Progressing on a CDK4/6 Inhibitor and Endocrine Therapy (31:46) Selective Estrogen Receptor Degraders (41:15) AKT (46:13) CME information and select publications
Send us Fan MailS4E4 The Oncology Journal Club Podcast In this special ASCO 2026 edition of The Oncology Journal Club, Craig Underhill, Chris Jackson and Kate Clarke unpack some of the meeting's most talked-about studies and discuss what they could mean for clinical practice.From the PROTEUS trial in high-risk prostate cancer and promising advances in RET fusion-positive lung cancer, to a rare sarcoma study demonstrating the potential of CDK4 inhibition, the team explores the data behind the headlines and highlights the challenges of translating trial results into real-world care.The episode also dives into what many are calling the breakthrough study of the meeting – the RESOLUTE-302 trial of daraxonrasib in previously treated pancreatic cancer. With a striking overall survival benefit in a disease that has seen few meaningful advances, the results sparked excitement throughout the oncology community.Along the way, the panel reflects on the atmosphere at ASCO, emerging trends in precision oncology, and how new therapeutic approaches such as KRAS inhibitors, bispecific antibodies and antibody-drug conjugates are reshaping the future of cancer treatment.The Oncology Journal Club Podcast is hosted by Professor Craig Underhill, Dr Kate Clarke and Professor Chris Jackson, and proudly produced by The Oncology NetworkVisit oncologynetwork.com.au for Show Notes, to send us Voice Notes and more information. And to download your bingo card if you'd like to play along with the team!
On this week's episode, Yaron Werber, Tess Cameron, SamFazeli, and Brian Skorney kick off with a look at markets, noting that while AI remains hot, biotech may be cooling amid anticipated tech IPOs. The co-hosts note that biotech saw a significant recovery over the past year driven by M&A and improving sentiment, highlighting that the XBI has remained remarkably stable. The discussion then turns to policy, where momentum to expand the COINS Act into biotech raises concerns. The group highlights the need to distinguish between manufacturing supply chains, where national security risks are real, and innovation ecosystems, where restricting capital flows could slow drug development and shift advantage outside of the US. Recapping the highlights from ASCO 2026, Akeso/Summit's ivonescimab showed meaningful survival benefits, while Revolution Medicines' KRAS program in pancreatic cancer stood out as a breakthrough, receiving a standing ovation at the conference. In breast cancer, the focus was centered on emerging CDK4 selective inhibitors from Pfizer and others. Grail's multi-cancer early detection readout was also discussed, along with in vivo CAR-T data from Kelonia that showed strong early responses but raised durability questions. *This episode aired on June 5, 2026.
En este último RECAP de la Reunión Anual de la Sociedad Americana de Oncología Clínica, el Dr. Fabián Martínez, oncólogo médico del Centro Médico ABC, dialoga con la Dra. Alejandra Martínez, oncóloga médica adscrita a la Clínica de Cáncer de Mama y Tumores Ginecológicos del Instituto Nacional de Ciencias Médicas y Nutrición, ambos de la Ciudad de México. La discusión inicia abordando el cáncer de mama avanzado con receptores hormonales positivos (RH+), destacando el estudio VIKTORIA-1, el cual evalúa el uso de gedatolisib frente al estándar con alpelisib en pacientes con progresión a inhibidores de CDK4/6 e inhibidores de aromatasa. Asimismo, se debate el papel de los degradadores selectivos del receptor de estrógeno (SERD) orales en primera línea y el valor de la intervención temprana ante la detección de mutaciones en ESR1 mediante biopsia líquida, a través del análisis del estudio SERENA-6 con camizestrant y su contexto frente a estudios como persevERA.El diálogo transita hacia el escenario de los tumores gastrointestinales con la revisión del estudio HERIZON-GEA-01 en adenocarcinoma gastroesofágico metastásico con sobreexpresión de HER2. Los expertos resaltan el beneficio clínico en supervivencia libre de progresión y supervivencia global al añadir zanidatamab y tislelizumab a la quimioterapia, con actividad observada independientemente del nivel de expresión de PD-L1. Posteriormente, se abordan los retos en el tratamiento del colangiocarcinoma irresecable o metastásico con rearreglos de FGFR2; al respecto, se analizan los datos de primera línea del estudio FIGHT-302 con pemigatinib frente a la quimioterapia en primera línea.Finalmente, se discuten los resultados de supervivencia del estudio TROPION-Breast02 en cáncer de mama triple negativo avanzado en pacientes no candidatas a inmunoterapia. Se destaca el beneficio consistente con el uso de datopotamab deruxtecan frente a la quimioterapia estándar. Referencia:Este contenido se basa en la interpretación crítica de la evidencia científica disponible, así como en la experiencia clínica del o los ponentes como profesionales de la salud en instituciones de referencia.Para profundizar en los conceptos discutidos, se recomienda al profesional de la salud consultar literatura científica vigente, guías clínicas internacionales y la normatividad aplicable en su país.Material exclusivo para profesionales de la salud. Este material ha sido desarrollado únicamente con fines educativos e informativos y no tiene la intención de sustituir el juicio clínico de los profesionales de la salud. Las opiniones y declaraciones presentadas en este contenido son responsabilidad exclusiva de los ponentes y no reflejan necesariamente la postura institucional de ScienceLink ni de terceros mencionados. La información presentada se basa en el conocimiento y la experiencia profesional de los ponentes. La veracidad, exactitud y actualidad científica de los datos son de su exclusiva responsabilidad. Así mismo garantizan que el contenido utilizado no infringe derechos de autor de terceros y asumen toda responsabilidad por su uso. Se deberán de revisar las indicaciones aprobadas en el país con estricto apego al marco regulatorio aplicable para cada uno de los tratamientos y medicamentos comentados. ASCO® es una marca registrada de la American Society of Clinical Oncology. Este material ha sido producido de manera independiente y no está autorizado, patrocinado ni avalado por dicha organización.
ASCOltaci: un podcast di OncoInfo in diretta da Chicago per ASCO2026 ASCOltaci è il podcast che ti aggiorna direttamente con la viva voce dei più autorevoli specialisti italiani dal congresso ASCO 2026 di Chicago. Le voci che contano… quando contano. Con uno sguardo tempestivo e critico, i nostri ospiti analizzano – a caldo – le novità che stanno ridisegnando le traiettorie della pratica clinica in oncologia. Strategie terapeutiche sempre più complesse, scelte che richiedono tempismo, visione e ascolto dei dati: dalla voce di chi quei dati li traduce in cura. Un podcast per chi vuole capire dove stiamo andando, mentre ci stiamo andando. Seguici sui nostri social Instagram (@drtalk_it) YouTube (DrTalk_it)
EVA CAST - o podcast do Grupo Brasileiro de Tumores Ginecológicos
O episódio 43 do EVA CAST, o podcast do Grupo Brasileiro de Tumores Ginecológicos, aborda como a oncologia de precisão vem transformando, na prática, o tratamento do câncer de ovário. Em um cenário marcado pelo avanço da biologia molecular, o episódio discute como testes genéticos, biomarcadores, inibidores de PARP, imunoterapia e novas terapias-alvo passaram a redefinir estratégias terapêuticas e ampliar as possibilidades de cuidado personalizado para as pacientes. Participam da conversa Mariana Scaranti, oncologista clínica da Rede Américas e diretora de pesquisa do EVA; Noele Gomes, oncologista clínica do Hospital São Domingos, no Maranhão; e Andreia Cristina de Melo, oncologista clínica da Oncologia Américas e chefe da Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico do INCA. Ao longo do episódio, as especialistas discutem como a caracterização molecular dos tumores ovarianos mudou a prática clínica nos últimos anos e passou a orientar desde a escolha da manutenção até o sequenciamento terapêutico em doença recorrente. Entre os principais pontos abordados estão os biomarcadores que atualmente impactam a tomada de decisão terapêutica, como BRCA1 e BRCA2, deficiência de recombinação homóloga (HRD), PD-L1, HER2, receptor de folato alfa e deficiência de mismatch repair. O episódio também detalha o momento ideal para realização de testes genéticos e moleculares e explica como essas informações passaram a influenciar diretamente a seleção de terapias-alvo e o manejo individualizado das pacientes. A conversa explora ainda os avanços recentes em diferentes subtipos da doença, incluindo o carcinoma seroso de baixo grau, com destaque para estudos envolvendo hormonioterapia, inibidores de CDK4/6 e drogas direcionadas à via MAP-quinase. Também são discutidos os resultados mais recentes apresentados em congressos internacionais, como estudos com anticorpos droga-conjugados, imunoterapia e novas estratégias para pacientes com doença resistente à platina. Outro eixo importante do episódio é o impacto dos inibidores de PARP na história natural do câncer de ovário, especialmente em pacientes com mutação em BRCA ou HRD positivo, além da discussão sobre como a doença começa a caminhar para um modelo de cuidado mais próximo ao de uma condição crônica, com múltiplas linhas de tratamento personalizadas ao longo do tempo. As especialistas também analisam os desafios de acesso no Brasil e em outros países de baixa e média renda, incluindo desigualdades entre sistemas público e privado e dificuldades na incorporação de testes e terapias inovadoras. Como mensagem final, as convidadas reforçam que a oncologia de precisão já deixou de ser uma perspectiva futura e passou a fazer parte do presente do tratamento do câncer de ovário, embora ainda existam barreiras importantes para garantir acesso amplo e equitativo às pacientes.
Marco Quarta is co-founder and Chief Scientific Officer of Rubedo Life Sciences, a precision-therapeutics company developing medicines that target the pathological cell states that drive age-associated disease. Marco's first appearance on the show was three years ago, in February 2023 (Episode 35), when Rubedo was a much earlier-stage company committed to the then-contrarian premise that "the senescent cell" is not a single entity but a heterogeneous family of cell states that needs to be deconvoluted at the single-cell level. In March 2026, Rubedo reported preliminary Phase 1b/2a clinical data for its lead candidate, RLS-1496, a first-in-class topical GPX4 modulator. Marco returns to the show to discuss what survived contact with human biology.In this episode, Chris and Marco unpack the readout from Rubedo's basket trial across four skin indications — psoriasis, atopic dermatitis, actinic keratosis, and photoaged skin — and the biology that underlies it. RLS-1496 came clean on safety in all four indications, with significant efficacy signals despite small patient numbers and short (20–30 day) treatment courses. More provocatively, the clinical and translational data have pushed Marco to redefine what kind of drug this actually is. Rather than a next-generation senolytic, GPX4 modulation appears to act as a state-gating intervention: it triggers ferroptosis in deeply senescent cells that have already crossed a redox threshold, while inducing a hormetic "redox reset" in stressed-but-recoverable cells that restores them to a healthier state. Marco proposes a new category to capture this dual action — adaptive senotherapeutics, or senoadaptive drugs — distinct from senolytics and senomorphics.The conversation traces the arc from Rubedo's founding thesis to a clinically validated platform (ALEMBIC, the AI-enabled single-cell multiomics engine that surfaced GPX4 as a target), through the strategic logic of leading with skin, into the broader question every longevity-biotech founder eventually has to answer: when does a disease-by-disease franchise become a credible preventive geroscience platform? Marco lays out the GLP-1 analogy explicitly — an anchor indication and a label-expansion roadmap that could carry GPX4 modulation from dermatology into respiratory, neurodegenerative, and metabolic disease, and ultimately into the use case where biomarkers of cellular senescence flag patients for therapy decades before disease becomes clinically apparent.The Finer Details:How Marco's 2023 contrarian view — that "senescent cells" hide a tissue- and state-specific reality — has been reinforced by the clinic, and how Rubedo's framing has shifted from "targeting senescent cells" to "targeting pathological cell states"The biology of GPX4 as a lipid-peroxidation gatekeeper, why senescent cells have intrinsic vulnerabilities (p16, p21, CDK4/6 inhibition) that make them ferroptosis-sensitive, and how Rubedo's approach differs from oncology-focused GPX4 programs at Takeda and othersThe "senoadaptive" mechanism — RLS-1496 eliminates GPX4-dependent senescent cells via ferroptosis while triggering NRF2/Keap1-driven redox reset, autophagy, and epigenetic remodeling in recoverable cells, restoring tissue trajectory from degenerative to regenerativeWhy Rubedo led with skin: clean regulatory path, accessible tissue, the ability to read out aging biology anddisease in the same trial, and a label-expansion runway into systemic indicationsPhase 1b (Europe) and Phase 2a (US) basket-trial results across psoriasis, atopic dermatitis, photoaged skin, and actinic keratosis: clean safety in 4/4 indications and significant efficacy signals — itch reduction in atopic dermatitis, decreased lesional thickness in psoriasis, target-engagement-correlated clinical improvement in photoaged skinThe richness of the translational dataset: biopsies, tape-stripping, spatial transcriptomics, proteomics, multiplex histomics, plasma biomarkers — all feeding back into ALEMBIC to refine the platformWhy actinic keratosis is the most strategically important indication — an age-related, chronic-inflammatory, precancerous condition where Rubedo can simultaneously test disease modification and biological-age reversalThe Rubedo–Beiersdorf partnership and the cosmetic vertical as a parallel commercial axisPipeline beyond skin: targeting aberrant basaloid stem cells in IPF and other pulmonary indications using different modalities (prodrugs, PROTACs, ADCs) to achieve cell-state selectivityThe longer-arc vision: senescence biomarkers as a "prediabetes-style" early signal, with senoadaptive drugs deployed decades before disease — and what a GLP-1-scale franchise might look like for GPX4 modulationQuotes:"There is not such a thing as a senescent cell — like there is not a cancer cell. And that was the initial idea. I'm glad that over time the field evolved. Now this is an accepted concept in the senotherapeutic space.""We are really talking about a dual function of RLS-1496 that can modulate the cell state depending on the adaptive response. That's why we call this — de facto — a new class of senotherapeutics. We call them adaptive senotherapeutics, or senoadaptive drugs — not a senolytic or a senomorphic, but working by modulating the cell state.""The best animal model for human therapies is human. As much as you can do preclinical work in animal models, it's always an approximation. We were able to test this directly in patients for safety, and in 4 out of 4 indications, we didn't have any safety signal.""Imagine you're taking care of a growing tree, and this tree has some dead leaves and some are a little bit stressed. If you shake the tree, the dead leaves will fall; the healthy leaves will not, because they're healthy and they resist the shake. But that shake actually gives the stressed leaves space and breathing room, and helps them to regain vitality. That's a little bit what GPX4 modulation does.""Senotherapeutics is a large, growing field — an untapped therapeutic opportunity. There is no such thing as a pan-senolytic or a pan-senotherapeutic, like there is no pan-oncotherapeutic. You need to understand the context. But these will all be part of the arsenal for true longevity medicine.""I don't see this as prevention of disease. The way I see therapies like ours, and the way the field of longevity is developing, is treating diseases decades before they develop. That's not a new concept — that's what we're doing in diabetes. You can be diagnosed with prediabetes today and reverse those biomarkers with lifestyle changes or metformin, and maybe never develop diabetes. That's exactly what we're doing here.""First of all, celebrating the first approved drugs from Rubedo — I don't think we're too far from that. But that's also a beginning, because you learn from the big momentum the GLP-1 agonists created: how a drug can start in one indication, create a new field, and prove that you can go beyond that. I hope in a few years we come back and talk about the next GLP-1 — this could be GPX4 modulators, or the senoadaptive drugs that are first in our pipeline."Links:Rubedo Life Sciences: https://www.rubedolife.comMarco Quarta's previous appearance on Translating Aging: Ep 35 — Targeting Pathologic Cells to Preserve Biological Youth
In today's episode, we welcomed Pedram Razavi, MD, PhD, and Dara S. Ross, MD. Dr Razavi is a breast medical oncologist and director of Liquid Biopsy & Genomics at Memorial Sloan Kettering Cancer Center in New York, New York. Dr Ross is an associate attending pathologist at Memorial Sloan Kettering Cancer Center.In our exclusive interview, Drs Razavi and Ross discussed the evolution of ESR1 mutation–directed breast cancer management, emphasizing the role of comprehensive genomic testing at metastatic recurrence, including liquid biopsy and tissue sequencing. They highlighted that ESR1 mutations can develop in patients receiving aromatase inhibitors and that the detection of these mutations is crucial for treatment decisions. They also highlighted findings from the phase 3 SERENA-6 trial (NCT04964934), which tested switching to camizestrant upon the emergence of an ESR1 mutation during treatment with an aromatase inhibitor and a CDK4/6 inhibitor ahead of radiographic disease progression in patients with hormone receptor–positive, HER2-negative metastatic breast cancer. Despite concerns from the FDA's Oncologic Drugs Advisory Committee (ODAC) about SERENA-6's design and overall survival outcomes, the experts praised the trial's innovative approach to personalizing breast cancer management based on biomarkers and noted ways that the ODAC decision may affect future clinical research in this field.
Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Sarah Sammons, MD Despite advances in the treatment of HR-positive HER2-negative advanced breast cancer, patients with PIK3CA-mutated disease who progress after a CDK4/6 inhibitor still face limited effective and tolerable treatment options.1 This unmet need has fueled interest in zovegalisib (formerly RLY-2608), a next generation, pan-mutant-selective PI3Kα inhibitor designed to spare wild-type protein and potentially reduce class-related toxicities.2 Dr. Sarah Sammons joins Dr. Charles Turck to review key findings from the first-in-human ReDiscover trial of zovegalisib + fulvestrant that supported initiation of the Phase 3 ReDiscover-2 study3,4, which is currently enrolling. They also discuss ReDiscover-2 eligibility criteria, along with patient selection and screening considerations, using hypothetical case scenarios. Dr. Sammons is the Associate Director of the Metastatic Breast Cancer Program at the Dana-Farber Cancer Institute in Boston, Massachusetts. References: Mishra R, Patel H, Alanazi S, Kilroy MK, Garrett JT. PI3K inhibitors in cancer: clinical implications and adverse effects. Int J Mol Sci. 2021;22(7)doi:10.3390/ijms22073464 Varkaris A, Pazolli E, Gunaydin H, et al. Discovery and clinical proof-of-concept of RLY-2608, a first-in-class mutant-selective allosteric PI3Kα inhibitor that decouples antitumor activity from hyperinsulinemia. Cancer Discovery. 2024;14(2):240–257. doi:10.1158/2159-8290.cd-23-0944 ClinicalTrials.gov. NCT06982521. Accessed April 12, 2026. https://clinicaltrials.gov/study/NCT06982521 Rugo HS, Saura C, Jhaveri K, et al. Poster PS5-08-25: …
Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Sarah Sammons, MD Despite advances in the treatment of HR-positive HER2-negative advanced breast cancer, patients with PIK3CA-mutated disease who progress after a CDK4/6 inhibitor still face limited effective and tolerable treatment options.1 This unmet need has fueled interest in zovegalisib (formerly RLY-2608), a next generation, pan-mutant-selective PI3Kα inhibitor designed to spare wild-type protein and potentially reduce class-related toxicities.2 Dr. Sarah Sammons joins Dr. Charles Turck to review key findings from the first-in-human ReDiscover trial of zovegalisib + fulvestrant that supported initiation of the Phase 3 ReDiscover-2 study3,4, which is currently enrolling. They also discuss ReDiscover-2 eligibility criteria, along with patient selection and screening considerations, using hypothetical case scenarios. Dr. Sammons is the Associate Director of the Metastatic Breast Cancer Program at the Dana-Farber Cancer Institute in Boston, Massachusetts. References: Mishra R, Patel H, Alanazi S, Kilroy MK, Garrett JT. PI3K inhibitors in cancer: clinical implications and adverse effects. Int J Mol Sci. 2021;22(7)doi:10.3390/ijms22073464 Varkaris A, Pazolli E, Gunaydin H, et al. Discovery and clinical proof-of-concept of RLY-2608, a first-in-class mutant-selective allosteric PI3Kα inhibitor that decouples antitumor activity from hyperinsulinemia. Cancer Discovery. 2024;14(2):240–257. doi:10.1158/2159-8290.cd-23-0944 ClinicalTrials.gov. NCT06982521. Accessed April 12, 2026. https://clinicaltrials.gov/study/NCT06982521 Rugo HS, Saura C, Jhaveri K, et al. Poster PS5-08-25: …
Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.In this episode, Nunnery sat down with Annie Bond, a breast cancer survivor and patient advocate.Diagnosed with breast cancer at age 26, Bond shared how her initial concerns about a breast lump were repeatedly dismissed by medical professionals who cited her youth and lack of a family history of breast cancer. It took months of persistence before she received a diagnosis, at which point the cancer had already spread to her liver.Bond emphasizes the necessity of self-advocacy and the value of seeking second or third medical opinions. Regarding fertility preservation, her first oncologist discouraged her from freezing her eggs, but her third oncologist provided a more personalized approach, using CDK4/6 inhibitors rather than immediate chemotherapy based on her luminal A disease subtype.A significant portion of the conversation focused on the mental health toll of cancer. Bond discusses the "warrior" stereotype, the guilt and shame she felt, and her struggle with post-traumatic stress disorder. She says she found critical support in community and support groups, which helped normalize her feelings and provided a sense of belonging.Regarding physical adverse effects, Bond detailed the challenges of medical menopause, including "menopause brain" and joint pain, which she manages through walking and stretching. She expressed frustration with health education that focuses on diet or alcohol as "blame" factors, noting that cancer can often develop regardless of lifestyle.Bond explained how she advocates for metastatic breast cancer research funding and the use of artificial intelligence risk assessment models to account for factors like breast density. Her mission is to increase early detection and ensure patients with metastatic disease are viewed with hope.
Love the podcast? Send us a text!In this episode of Breast Cancer Conversations, Laura speaks with Virginia Rodriguez, who was diagnosed with stage 4 de novo metastatic breast cancer after experiencing progressive weakness, digestive issues, dehydration, and a dramatic decline in her ability to walk and function.Virginia shares what it was like to go from hiking the Camino de Santiago to struggling to climb the stairs in her own home, the emotional experience of finally receiving a diagnosis after months of unanswered symptoms, and how her care team identified breast cancer that had spread to multiple areas, including her brain, spine, liver, spleen, and bones.Virginia was placed on Verzenio, also known as abemaciclib, as part of her first line of treatment. Verzenio is an oral CDK4/6 inhibitor used in certain HR-positive, HER2-negative advanced or metastatic breast cancers, including in combination with endocrine therapy depending on a person's treatment history and clinical situationSupport the showListener FeedbackIf this episode resonated with you, we invite you to leave a review on Apple Podcasts or Spotify.You can also click the link in the show notes that says "Love this episode? Send us a text" to share feedback.Messages are completely anonymous.If you would like us to follow up directly, please include your email address in your message so we can respond.Latest News: Join our Mailing List - New content drops every Monday! Discover FREE programs, support groups, and resources from SurvivingBReastCancer.org! Become a Breast Cancer Conversations+ Member! Sign Up Now. Enjoying our content? Please consider supporting our work.
En este nuevo episodio del pódcast BreastLink, dedicado al análisis del impacto del estudio lidERA, el Dr. Juan Carlos Samamé conduce una conversación con dos de los coautores principales del estudio y figuras referentes del Grupo Español de Investigación en Cáncer de Mama (GEICAM): el Dr. Miguel Martín, oncólogo médico, catedrático de la Universidad Complutense de Madrid y jefe de servicio en el Hospital Gregorio Marañón, en Madrid; y el Dr. Manuel Ruiz Borrego, encargado del área de cáncer de mama del Hospital Virgen del Rocío en Sevilla, ambos en España.El debate se centra en el cambio de paradigma que supone la introducción de giredestrant, un degradador selectivo del receptor de estrógeno oral (SERD), en el escenario de la adyuvancia para pacientes con cáncer de mama luminal precoz. Los expertos analizan cómo este fármaco logra superar los resultados de la terapia endocrina estándar, ofreciendo una mejor tolerabilidad y eficacia en poblaciones de riesgo intermedio y alto.En la conversación se plantearon las siguientes preguntas:¿Cuál es el racional científico detrás del estudio lidERA?¿Qué diseño y objetivos tuvo el estudio fase III?¿Cómo se define la población de riesgo incluida?¿Qué significan los resultados de eficacia y seguridad para la práctica clínica?¿Cómo se posiciona lidERA frente a otros avances como los inhibidores de CDK4/6? Fecha de grabación: 24 de marzo de 2026.Referencia:Este contenido se basa en la interpretación crítica de la evidencia científica disponible, así como en la experiencia clínica del o los ponentes como profesionales de la salud en instituciones de referencia.Para profundizar en los conceptos discutidos, se recomienda al profesional de la salud consultar literatura científica vigente, guías clínicas internacionales y la normatividad aplicable en su país.Material exclusivo para profesionales de la salud. Este material ha sido desarrollado únicamente con fines educativos e informativos y no tiene la intención de sustituir el juicio clínico de los profesionales de la salud. Las opiniones y declaraciones presentadas en este contenido son responsabilidad exclusiva de los ponentes y no reflejan necesariamente la postura institucional de ScienceLink ni de terceros mencionados. La información presentada se basa en el conocimiento y la experiencia profesional de los ponentes. La veracidad, exactitud y actualidad científica de los datos son de su exclusiva responsabilidad. Así mismo garantizan que el contenido utilizado no infringe derechos de autor de terceros y asumen toda responsabilidad por su uso.
Love the podcast? Send us a text!Jennifer Tipton was in her mid-forties, running a yoga business in California, teaching indoor cycling classes, and training clients when she was diagnosed with stage 3 estrogen-positive breast cancer at the start of 2021. Her entire year — AC chemotherapy, then Taxol, then a lumpectomy, then a double mastectomy with a DIEP flap reconstruction, then 33 rounds of radiation — was consumed by treatment. By the end of it, she was exhausted in a way most people can't quite imagine.And then her oncologist told her about Verzenio (abemaciclib), a CDK4/6 inhibitor prescribed to help reduce the risk of recurrence in certain patients.We discuss: • what it felt like transitioning from active treatment to long-term medication • how movement and exercise helped her maintain energy and resilience • strategies she used to manage GI side effects during daily life • the emotional complexity of long-term cancer therapy • what improved after completing treatment • advice for patients deciding whether Verzenio is right for themSupport the showListener FeedbackIf this episode resonated with you, we invite you to leave a review on Apple Podcasts or Spotify.You can also click the link in the show notes that says "Love this episode? Send us a text" to share feedback.Messages are completely anonymous.If you would like us to follow up directly, please include your email address in your message so we can respond.Latest News: Join our Mailing List - New content drops every Monday! Discover FREE programs, support groups, and resources from SurvivingBReastCancer.org! Become a Breast Cancer Conversations+ Member! Sign Up Now. Enjoying our content? Please consider supporting our work.
Love the podcast? Send us a text!Every breast cancer treatment plan is highly personalized, and understanding potential side effects can help patients feel more prepared, informed, and empowered throughout care.In this episode of Breast Cancer Conversations, Laura speaks with Debbie Ciak, a breast cancer survivor diagnosed with Stage 2B ER/PR-positive, HER2-negative breast cancer with lymph node involvement.Due to features associated with a higher risk of recurrence, Debbie's care team recommended treatment with Verzenio (abemaciclib), a CDK4/6 inhibitor commonly prescribed alongside endocrine therapy for certain HR+, HER2- breast cancers.During treatment, Debbie experienced significant gastrointestinal symptoms and later developed respiratory symptoms that were ultimately identified as drug-induced interstitial lung disease (ILD), also known as pneumonitis.Debbie also shares how integrative support resources and survivorship programming helped her continue moving forward after treatment.Her story underscores the importance of individualized care, ongoing monitoring, and open communication between patients and healthcare providers when incorporating newer therapies into treatment plans.While every patient responds differently to therapy, conversations like this help support more informed discussions between patients and their care teams.Topics Covered• Stage 2B ER/PR+ breast cancer diagnosis • understanding recurrence risk factors • treatment decision-making • why Verzenio was recommended • managing common CDK4/6 inhibitor side effects • Debbie's experience with ILD/pneumonitis • recognizing respiratory symptoms early • coordinating care across oncology and pulmonology • survivorship and ongoing monitoring • exercise and recovery • patient empowerment and advocacyThis episode is part of an ongoing series sharing real-world patient experiences on various therapies, highlighting the importance of education, communication, and personalized treatment decisions in breast cancer care.Support the showListener FeedbackIf this episode resonated with you, we invite you to leave a review on Apple Podcasts or Spotify.You can also click the link in the show notes that says "Love this episode? Send us a text" to share feedback.Messages are completely anonymous.If you would like us to follow up directly, please include your email address in your message so we can respond.Latest News: Become a Breast Cancer Conversations+ Member! Sign Up Now. Join our Mailing List - New content drops every Monday! Discover FREE programs, support groups, and resources from SurvivingBReastCancer.org! Enjoying our content? Please consider supporting our work.
In this podcast, experts Ann H. Partridge, MD, MPH; Saranya Chumsri, MD; and William J. Gradishar, MD, FASCO, FACP, discuss the roles of adjuvant chemotherapy and CDK4/6 inhibitors and neoadjuvant checkpoint inhibitors for patients with early-stage, hormone receptor–positive breast cancer.
In this episode, Danielle Roman, PharmD, BCOP, and Jordan Hill, PharmD, BCOP, discuss patient-centered management of CDK4/6 inhibitor therapy in HR-positive/HER2-negative breast cancer, with a focus on how oncology pharmacists and the multidisciplinary care team can support patients through treatment, including: Practical strategies for monitoring and managing key adverse events associated with abemaciclib, ribociclib, and palbociclib, such as diarrhea, neutropenia, hepatotoxicity, and QT prolongation How dose interruptions and dose reductions can help improve tolerability while maintaining clinical benefit Real-world approaches to patient education, toxicity counseling, and communication that can improve adherence and persistence with oral CDK4/6 inhibitor therapy Additional considerations such as financial toxicity, coordination with specialty pharmacy, and practical tools to help patients stay on therapy over the long term Get access to all of our new podcasts by subscribing to the Decera Clinical Education Oncology Podcast on Apple Podcasts, YouTube Music, or Spotify. Presenters: Danielle Roman, PharmD, BCOP Manager, Oncology Clinical Pharmacy Services Oncology Clinical Pharmacy Specialist Allegheny Health Network Pittsburgh, Pennsylvania Jordan Hill, PharmD, BCOP Clinical Pharmacy Specialist, Breast Oncology West Virginia University Cancer Institute Morgantown, West Virginia Link to full program:https://bit.ly/4cIYca6 Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.
Did you know prior CDK4/6 duration may be prognostic for identifying patients more likely to benefit from single-agent oral SERDs? Credit available for this activity expires: 04/07/2027 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/enhancing-clinical-understanding-oral-serd-based-therapies-2026a1000a46?ecd=bdc_podcast_libsyn_mscpedu
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BRB865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until March 26, 2027.Raising the Bar for Survival in High-Risk HR+, HER2- EBC: A Practical Framework for the Adjuvant Setting; Real-World Strategies to Improve Risk Assessment, Candidate Identification, Differentiated CDK4/6i + ET Selection, and Optimal Treatment Delivery 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 Lilly.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BRB865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until March 26, 2027.Raising the Bar for Survival in High-Risk HR+, HER2- EBC: A Practical Framework for the Adjuvant Setting; Real-World Strategies to Improve Risk Assessment, Candidate Identification, Differentiated CDK4/6i + ET Selection, and Optimal Treatment Delivery 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 Lilly.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BRB865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until March 26, 2027.Raising the Bar for Survival in High-Risk HR+, HER2- EBC: A Practical Framework for the Adjuvant Setting; Real-World Strategies to Improve Risk Assessment, Candidate Identification, Differentiated CDK4/6i + ET Selection, and Optimal Treatment Delivery 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 Lilly.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BRB865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until March 26, 2027.Raising the Bar for Survival in High-Risk HR+, HER2- EBC: A Practical Framework for the Adjuvant Setting; Real-World Strategies to Improve Risk Assessment, Candidate Identification, Differentiated CDK4/6i + ET Selection, and Optimal Treatment Delivery 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 Lilly.Disclosure information is available at the beginning of the video presentation.
In this episode, oncology pharmacists Julia L. Ziegengeist, PharmD, BCOP, and Rodney Hunter, PharmD, BCOP, explore and challenge common assumptions about adjuvant CDK4/6 inhibitor use in high-risk HR+/HER2- early breast cancer, offering insights on patient selection, trial nuances, toxicity management, and real-world decision-making. Presenters: Rodney Hunter, PharmD, BCOP Director of Clinical Services Memorial Hermann Texas Medical Center Clinical Pharmacy Specialist University of Texas Health Memorial Hermann Cancer Center Professor Texas Southern University College of Pharmacy and Health Sciences Clinical Adjunct Professor McGovern Medical School Houston, Texas Julia L. Ziegengeist, PharmD, BCOP Clinical Pharmacist Specialist, Breast Medical Oncology Levine Cancer, Atrium Health Charlotte, North Carolina Link to full program:https://bit.ly/46SPGlU Get access to all of our new podcasts by subscribing to the Decera Clinical Education Oncology 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 an interview with Dr Lajos Pusztai, including the following topics: Circulating tumor DNA monitoring for patients with ER-positive, HER2-negative high-risk breast cancer during adjuvant endocrine therapy (0:00) Clinical performance of a whole-genome assay for predicting disease recurrence (5:52) Using circulating tumor DNA status to personalize CDK4/6 inhibitor therapy (12:46) Neoadjuvant and adjuvant therapy stratified by circulating tumor DNA status (21:11) Utility of circulating tumor DNA status in the management of metastatic breast cancer (24:55) 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. Today, we're diving into a series of significant updates that underscore the dynamic nature of these industries, marked by scientific advancements, regulatory shifts, and strategic adjustments.A federal judge in Boston recently made headlines by halting key components of Robert F. Kennedy Jr.'s proposed vaccine overhaul. This decision has far-reaching implications for public health policy, particularly affecting the Health and Human Services' vaccination agenda and the Advisory Committee on Immunization Practices. The intervention highlights the complex interplay between legal frameworks and healthcare policies, especially in an era where vaccine strategies are pivotal for global health security. This judicial decision comes amid broader societal debates about vaccine safety, efficacy, and autonomy—issues that remain critical as we navigate ongoing public health challenges.In a major move within scientific innovation, Roche has partnered with NVIDIA to integrate artificial intelligence into drug and diagnostic development. By leveraging NVIDIA's AI capabilities, Roche aims to streamline its R&D processes, enhancing precision medicine approaches. This collaboration exemplifies the growing trend of incorporating advanced computational technologies in biopharma to optimize drug discovery and development pipelines. The potential reduction in time-to-market for new therapies could significantly impact patient care by accelerating access to innovative treatments.Turning to clinical trials, Pfizer's CDK4 inhibitor, atirmociclib, has shown promising results in a Phase 2 trial for second-line metastatic breast cancer. The trial met its primary endpoint of improving progression-free survival, signaling atirmociclib's potential as a therapeutic option. Pfizer's strategic focus on earlier lines of treatment indicates a shift towards expanding indications for promising drug candidates, which could enhance outcomes for a broader patient population. This development aligns with Pfizer's efforts to maintain its oncology portfolio amidst impending patent expirations on key products.Conversely, Rhythm Pharmaceuticals has faced setbacks with its MC4R agonist, Imcivree, which failed to meet primary BMI endpoints across four genetic obesity subgroups in a Phase 3 trial. This outcome underscores the challenges inherent in developing treatments for complex genetic conditions and highlights the necessity for robust clinical trial designs to accurately evaluate therapeutic efficacy.The geopolitical landscape also impacts the industry significantly. Ongoing tensions involving Iran pose risks to drug shipments from the Middle East, particularly those requiring cold chain logistics such as biologics and generics. This situation could have long-term repercussions on US manufacturing capabilities and generic drug availability. Companies must consider strategic adjustments in supply chain management and sourcing strategies to mitigate these risks.On the market strategy front, Biovie's plan for a $20 million IPO reflects an industry trend towards repurposing existing drugs to address unmet medical needs. By developing a new formulation of an approved low blood pressure drug for liver disease treatment, Biovie aims to optimize its mature product portfolio amid pricing pressures and competitive markets.Another significant regulatory development saw Alcon abandon its $356 million acquisition deal with Lensar following scrutiny from the Federal Trade Commission (FTC). This decision illustrates the regulatory challenges companies face in pursuing mergers and acquisitions. While regulatory oversight ensures market competitiveness, it necessitates careful strategic planning by companies seeking expansion through acquisitions.Further illustrating the evolving reSupport the show
In this episode of JCO Article Insights, host Dr. Melis Canturk summarizes the article, "Phase 2 Trial of Ribociclib plus Letrozole in Women with Recurrent Low-Grade Serous Cancer of the Ovary, Fallopian Tube, or Peritoneum: A GOG Partners Trial," by Slomovitz et al. TRANSCRIPT Melis Canturk: Hello, and welcome to JCO Article Insights. I'm your host, Melis Canturk, and today we will be discussing the JCO article, "Phase 2 Trial of Ribociclib plus Letrozole in Women with Recurrent Low-Grade Serous Cancer of the Ovary, Fallopian Tube, or Peritoneum: A GOG Partners Trial." Building on the fact that more than 95% of low-grade serous carcinoma are estrogen receptor positive and often exhibit abnormalities in the CDK4/6 signaling pathway, researchers launched the GOG 3026 trial. This study investigated the effectiveness of pairing the CDK4/6 inhibitor ribociclib with letrozole, an aromatase inhibitor, adapting a therapeutic approach that has already transformed the treatment landscape for hormone receptor-positive metastatic breast cancer. Low-grade serous ovarian cancer is a rare malignancy characterized by its hormonally driven nature and relative resistance to traditional platinum-based chemotherapy. While it's associated with longer survival than high-grade serous carcinoma, recurrent disease presents a significant clinical challenge due to low response rates to standard treatments. The GOG 3026 trial was an open-label, single-arm, multicenter, phase 2 study that enrolled 51 women with measurable, recurrent, low-grade serous ovarian cancer. To ensure diagnostic accuracy, all cases underwent central pathology review. Participants were required to be at least 18 years old with an ECOG performance status of 0 to 2. While there was no limit on the number of prior therapies, patients were excluded if they had previously used CDK4/6 inhibitors. Prior endocrine therapy was permitted only if the patient had discontinued it at least 6 months before the study and had not experienced disease progression while on that specific therapy. Additionally, women with intact ovarian function were required to undergo ovarian suppression. The treatment regimen consisted of 600 mg of oral ribociclib daily for the first 21 days of a 28-day cycle, paired with a continuous daily dose of 2.5 mg of letrozole. The trial's primary endpoint was the investigator-assessed objective response rate. The results were clinically meaningful. The confirmed overall response rate was 30.6%, which included one complete response and 14 partial responses. The clinical benefit rate, which includes stable disease, reached 84%. These outcomes are particularly notable given the heavily pretreated study population, where nearly 40% of patients had received three or more prior lines of systemic therapy. Durability and survival data further underscored the potential of this combination. Among those who responded to treatment, the median duration of response was 21.2 months. The median progression-free survival was 14.5 months, and the median overall survival reached 44.5 months. In terms of safety, the profile was consistent with previous CDK4/6 inhibitor studies. The most common grade 3 and 4 adverse event was neutropenia, occurring in 47% of patients. However, it was asymptomatic and managed through dose modification. Only 4% of patients discontinued the trial due to adverse events, and no dose-limiting toxicities were observed. When comparing these results to other therapeutic benchmarks, the ribociclib-letrozole combination demonstrated more favorable outcomes than historical endocrine monotherapy. It yields response rates of only 13% to 14%. Furthermore, while MEK inhibitors like trametinib or the combination of avutometinib defactinib show similar response rates, the ribociclib-letrozole regimen displayed significantly better tolerability. Specifically, only 4% of patients in this trial discontinued the therapy due to adverse events, compared to much higher discontinuation rates seen with MEK inhibitor strategies. In conclusion, the GOG 3026 trial successfully establishes ribociclib plus letrozole as a clinically active and well-tolerated regimen for recurrent low-grade serous ovarian cancer. By achieving durable disease control in a heavily pretreated, relatively chemoresistant population, this combination may redefine the therapeutic paradigm for this rare cancer. These findings support the continued evaluation of CDK4/6 endocrine strategies as a preferred chemotherapy-sparing option that prioritizes both disease control and patients' quality of life. Thank you for tuning into JCO Article Insights. Don't forget to subscribe and join us next time as we explore more groundbreaking research shaping the future of oncology. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
In this episode of the Oncology Brothers podcast we navigated the rapidly evolving treatment landscape of Metastatic Hormone Receptor-Positive Breast Cancer. We were joined by Dr. Kevin Kalinsky, Director of the Breast Cancer Program at the Winship Cancer Institute, Emory University, to discuss the implications of new targeted therapies, optimal sequencing strategies, and practical toxicity management. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: • YouTube: https://www.youtube.com/@oncologybrothers • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ The discussion covered: • The critical role of NGS testing (tissue vs. liquid biopsy) in identifying PIK3CA, ESR1, AKT1 and PTEN alterations. • Frontline management of high-risk, endocrine-resistant disease with the inavolisib triplet (INAVO120) and its overall survival benefit. • Choosing between CDK4/6 inhibitors (abemaciclib vs. ribociclib) in de novo metastatic disease. • Post-CDK4/6 inhibitors on progression we covered, the use of oral SERDs (imlunestrant) and AKT inhibitors (capivasertib). • The "ADC explosion", sequencing T-DXd (DESTINY-Breast06), sacituzumab govitecan (TROPiCS-02), and datopotamab deruxtecan (TROPION-Breast01). • Clinical pearls for managing toxicities: stomatitis, hyperglycemia, rash, neutropenia, and ILD. Join us as we break down the latest data and provide actionable insights for the practicing oncologist. Don't forget to subscribe for more episodes in our breast cancer algorithm series! #MetastaticBreastCancer, #HRPositive, #ADCsequencing, #PIK3CA-AKT, #OncologyPodcast, #OncologyBrothers
JCO PO author Dr. Foldi at UPMC Hillman Cancer Center and University of Pittsburgh School of Medicine shares insights into the JCO PO article, "Personalized Circulating Tumor DNA Testing for Detection of Progression and Treatment Response Monitoring in Patients With Metastatic Invasive Lobular Carcinoma of the Breast." Host Dr. Rafeh Naqash and Dr. Foldi discuss how serial ctDNA testing in patients with mILC is feasible and may enable personalized surveillance and real-time therapeutic monitoring. 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 am your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, we are thrilled to be joined by Dr. Julia Foldi, Assistant Professor of Medicine in the Division of Hematology-Oncology at University of Pittsburgh School of Medicine and the Magee-Womens Hospital of the UPMC. She is also the lead and corresponding author of the JCO Precision Oncology article entitled "Personalized Circulating Tumor DNA Testing for Detection of Progression and Treatment Response Monitoring in Patients with Metastatic Invasive Lobular Carcinoma of the Breast." At the time of this recording, our guest's disclosures will be linked in the transcript. Julia, welcome to our podcast, and thank you for joining us today. Dr. Julia Foldi: Thank you so much for having me. It is a pleasure. Dr. Rafeh Naqash: Again, your manuscript and project address a few interesting things, so we will start with the basics, since we have a broad audience that comprises trainees, community oncologists, and obviously precision medicine experts as well. So, let us start with invasive lobular breast carcinoma. I have been out of fellowship for several years now, and I do not know much about invasive lobular carcinoma. Could you tell us what it is, what some of the genomic characteristics are, why it is different, and why it is important to have a different way to understand disease biology and track disease status with this type of breast cancer? Dr. Julia Foldi: Yes, thank you for that question. It is really important to frame this study. So, lobular breast cancers, which we shorten to ILC, are the second most common histologic subtype of breast cancer after ductal breast cancers. ILC makes up about 10 to 15 percent of all breast cancers, so it is relatively rare, but in the big scheme of things, because breast cancer is so common, this represents actually over 40,000 new diagnoses a year in the US of lobular breast cancers. What is unique about ILC is it is characterized by loss of an adhesion molecule, E-cadherin. It is encoded by the CDH1 gene. What it does is these tumors tend to form discohesive, single-file patterns and infiltrate into the tumor stroma, as opposed to ductal cancers, which generally form more cohesive masses. As we generally explain to patients, ductal cancers tend to form lumps, while lobular cancers often are not palpable because they infiltrate into the stroma. This creates several challenges, particularly when it comes to imaging. In the diagnostic setting, we know that mammograms and ultrasounds have less sensitivity to detect lobular versus ductal breast cancer. When it comes to the metastatic setting, conventional imaging techniques like CT scans have less sensitivity to detect lobular lesions often. One other unique characteristic of ILC is that these tumors tend to have lower proliferation rates. Because our glucose-based PET scans depend on glucose uptake of proliferating cells, often these tumors also are not avid on conventional FDG-PET scans. It is a challenge for us to monitor these patients as they go through treatment. If you think about the metastatic setting, we start a new treatment, we image people every three to four cycles, about every three months, and we combine the imaging results with clinical assessment and tumor markers to decide if the treatment is working. But if your imaging is not reliable, sometimes even at diagnosis, to really detect these tumors, then really, how are we following these patients? This is really the unique challenge in the metastatic setting in patients with lobular breast cancer: we cannot rely on the imaging to tell if patients are responding to treatment. This is where liquid biopsies are really, really important, and as the field is growing up and we have better and better technologies, lobular breast cancer is going to be a field where they are going to play an important role. Dr. Rafeh Naqash: Thank you for that easy-to-understand background. The second aspect that I would like to have some context on, to help the audience understand why you did what you did, is ctDNA, tumor informed and non-informed. Could you tell us what these subtypes of liquid biopsies are and why you chose a tumor informed assay for your study? Dr. Julia Foldi: Yes, it is really important to understand these differences. As you mentioned, there are two main platforms for liquid biopsy assays, circulating tumor DNA assays. I think what is more commonly used in the metastatic setting are non-tumor informed assays, or agnostic assays. These are generally next-generation sequencing-based assays that a lot of companies offer, like Guardant, Tempus, Caris, and FoundationOne. These do not require tumor tissue; they just require a blood sample, a plasma sample, essentially. The next-generation sequencing is done on cell-free DNA that is extracted from the plasma, and it is looking for any cell-free DNA and essentially, figuring out what part of the cell-free DNA comes from the tumor is done through a bioinformatics approach. Most of these assays are panel tests for cancer-associated mutations that we know either have therapeutic significance or biologic significance. So, the results we receive from these tests generally read out specific mutations in oncogenic genes, or sometimes things like fusions where we have specific targeted drugs. Some of the newer assays can also read out tumor fraction; for example, the newest generation Guardant assay that is methylation-based, they can also quantify tumor fraction. But the disadvantage of the tumor agnostic approach is that it is a little bit less sensitive. Opposed to that, we have our tumor informed tests, and these require tumor tissue. Essentially, the tumor is sequenced; this can either be whole exome or whole genome sequencing. The newer generation assays are now using whole genome sequencing of the tumor tissue, and a personalized, patient-specific panel of alterations is essentially barcoded on that tumor tissue. This can be either structural variants or it can be mutations, but generally, these are not driver mutations, but sort of things that are present in the tumor tissue that tend to stay unchanged over time. For each particular patient, a personalized assay, if you want to call it a fingerprint or barcode, is created, and then that is what then is used to test the plasma sample. Essentially, you are looking for that specific cancer in the blood, that barcode or fingerprint in the blood. Because of this, this is a much more sensitive way of looking for ctDNA, and obviously, this detects only that particular tumor that was sequenced originally. So, it is much more sensitive and specific to that tumor that was sequenced. You can argue for both approaches in different settings. We use them in different settings because they give us different information. The tumor agnostic approach gives us mutations, which can be used to determine what the next best therapy to use is, while the tumor informed assay is more sensitive, but it is not going to give us information on therapeutic targets. However, it is quantified, and we can follow it over time to see how it changes. We think that it is going to tell us how patients respond to treatment because we see our circulating tumor DNA levels rise and fall as the cancer burden increases or decreases. We decided to use the tumor informed approach in this particular study because we were really interested in how to determine if patients are having response to treatment versus if they are going to progress on their treatment, more so than looking for specific mutations. Dr. Rafeh Naqash: When you think about these tumor informed assays and you think about barcoding the mutations on the original tumor that you try to track or follow in subsequent blood samples, plasma samples, in your experience, if you have done it in non-lobular cancers, do you think shedding from the tumor has something to do with what you capture or how much you capture? Dr. Julia Foldi: Absolutely. I think there are multiple factors that go into whether someone has detectable ctDNA or not, and that has to do with the type of cancer, the location, right, where is the metastatic site? This is something that we do not fully understand yet: what are tumors that shed more versus not? There is also clearance of ctDNA, and so how fast that clearance occurs is also something that will affect what you can detect in the blood. ctDNA is very short-lived, only has a half-life of hours, and so you can imagine that if there is little shedding and a lot of excretion, then you are not going to be detecting a lot of it. In general, in the metastatic setting, we see that we can detect ctDNA in a lot of cases, especially when patients are progressing on treatment, because we imagine their tumor burden is higher at that point. Even with the non-tumor informed assays, we detect a lot of ctDNA. Part of this study was to actually assess: what is the proportion of patients where we can have this information? Because if we are only going to be able to detect ctDNA in less than 50 percent of patients, then it is not going to be a useful method to follow them with. Because this field is new and we have not been using a lot of tumor informed assays in the metastatic setting, we did not really know what to expect when we set out to look at this. We did not know what was going to be the baseline detection rate in this patient population, so that was one of the first things that we wanted to answer. Dr. Rafeh Naqash: Excellent. Now going to this manuscript in particular, what was the research question, what was the patient population, and what was the strategy that you used to investigate some of these questions? Dr. Julia Foldi: So, we partnered with Natera, and the reason was that their Signatera tumor-informed assay was the first personalized, tumor-informed, really an MRD assay, minimal residual disease detection assay. It has been around the longest and has been pretty widely used commercially already, even though some of our data is still lacking. but we know that people are using this in the real world. We wanted to gather some real-world data specifically in lobular patients. So, we asked Natera to look at their database of commercial Signatera testing and look for patients with stage 4 lobular breast cancer. The information all comes from the submitting physicians sending in pathologic reports and clinical notes, and so they have that information from the requisitions essentially that are sent in by the ordering physician. We found 66 patients who were on first-line or close to first-line endocrine-based therapies for their metastatic lobular breast cancer and had serial collections of Signatera tests. The way we defined baseline was that the first Signatera had to be sent within three months of starting treatment. So, it is not truly baseline, but again, this is a limitation of looking at real-world data is that you are not always going to get the best time point that you need. We had over 350 samples from those 66 patients, again longitudinal ctDNA samples, and our first question was what is the baseline detection rate using this tumor informed assay? Then, most importantly, what is the concordance between changes in ctDNA and clinical response to treatment? That is defined by essentially radiologic response to treatment. Dr. Rafeh Naqash: Interesting. So, what were some of your observations in terms of ctDNA dynamics, whether baseline levels made a difference, whether subsequent levels at different time points made a difference, or subsequent levels at, let us say, cycle three made a difference? Were there any specific trends that you saw? Dr. Julia Foldi: So, first, at baseline, 95 percent of patients had detectable ctDNA, which is, I think, a really important data point because it tells us that this can be a really useful test. If we can detect it in almost all patients before they start treatment, we are going to be able to follow this longitudinally. And again, these were not true baseline samples. So, I think if we look really at baseline before starting treatment, almost all patients will have detectable ctDNA in the metastatic setting. The second important thing we saw was that disease progression correlated very well with increase in ctDNA. So, in most patients who had disease progression by imaging, we saw increase in ctDNA. Conversely, in most patients who had clinical benefit from their treatment, so they had a response or stable disease, we saw decrease in ctDNA levels. It seems that what we call molecular response based on ctDNA is tracking very nicely along with the radiographic response. So, those were really the two main observations. Again, this is a small cohort, limited by its real-world nature and the time points that ctDNA assay was sent was obviously not mandated. This is a real-world data set, and so we could not really look at specific time points like you asked about, let us say, cycle three of therapy, right? We did not have all of the right time points for all of the patients. But what we were able to do was to graph out some specific patient scenarios to illustrate how changes in ctDNA correlate with imaging response. I can talk a little bit about that. Dr. Rafeh Naqash: That was going to be my question. Did you see patients who had serial monitoring using the tumor informed ctDNA assay where the assay became positive a few months before the imaging? Did you have any of those kinds of observations? Dr. Julia Foldi: Yes, so I think this is where the field is going: are we able to use this technology to maybe detect progression before it becomes clinically apparent? Of course, there are lots of questions about: does that really matter? But it seems like, based on some of the patient scenarios that we present in the paper, that this testing can do that. So, we had a specific scenario, and this is illustrated in a figure in the paper, really showing the treatment as well as the changes in ctDNA, tumor markers, and also radiographic response. So, this particular patient was on first-line endocrine therapy and CDK4/6 inhibitor with palbociclib. Initially, she had a low-level detectable ctDNA. It became undetectable during treatment, and the patient had a couple of serial ctDNA assays that were negative, so undetectable. And then we started, after about seven months on this combination therapy, the ctDNA levels started rising. She actually had three serial ctDNA assays with increasing level of ctDNA before she even had any imaging tests. And then around the time that the ctDNA peaked, this patient had radiographic evidence of progression. There was also an NGS-based assay sent to look for specific mutations at that point. The patient was found to have an ESR1 mutation, which is very common in this patient population. She was switched to a novel oral SERD, elacestrant, and the ctDNA fell again to undetectable within the first couple months of being on elacestrant. And then a very similar thing happened: while she was on this second-line therapy, she had three serial negative ctDNA assays, and then the fourth one was positive. This was two months before the patient had a scan that showed progression again. Dr. Rafeh Naqash: And Julia, like you mentioned, this is a small sample size, limited number of patients, in this case, one patient case scenario, but provides insights into other important aspects around escalation or de-escalation of therapy where perhaps ctDNA could be used as an integral biomarker rather than an exploratory biomarker. What are some of your thoughts around that and how is the breast cancer space? I know like in GI and bladder cancer, there has been a significant uptrend in MRD assessments for therapeutic decision making. What is happening in the breast cancer space? Dr. Julia Foldi: So, super interesting. I think this is where a lot of our different fields are going. In the breast cancer space, so far, I have seen a lot of escalation attempts. It is not even necessarily in this particular setting where we are looking at dynamics of ctDNA, but in the breast cancer world, of course, we have a lot of data on resistance mutations. I mentioned ESR1 mutation in a particular patient in our study. ESR1 mutations are very common in patients with ER-positive breast cancer who are on long-term endocrine therapy, and ESR1 mutations confer resistance to aromatase inhibitors. So, that is an area that there has been a lot of interest in trying to detect ESR1 mutations earlier and switching therapy early. So, this was the basis of the SERENA-6 trial, which was presented last year at ASCO and created a lot of excitement. This was a trial where patients had non-tumor-informed NGS-based Guardant assay sent every three to six months while they were on first-line endocrine therapy with a CDK4/6 inhibitor. If they had an ESR1 mutation detected, they were randomized to either continue the same endocrine therapy or switch to an oral SERD. The trial showed that the population of patients who switched to the oral SERD did better in terms of progression-free survival than those who stayed on their original endocrine therapy. There are a lot of questions about how to use this in routine practice. Of course, it is not trivial to be sending a ctDNA assay every three to six months. The rate of detection of these mutations was relatively low in that study; again, the incidence increases in later lines of therapy. So, there are a lot of questions about whether we should be doing this in all of our first-line patients. The other question is, even the patients who stayed on their original endocrine therapy were able to stay on that for another nine months. So, there is this question of: are we switching patients too early to a new line of therapy by having this escalation approach? So, there are a lot of questions about this. As far as I know, at least in our practice, we are not using this approach just yet to escalate therapy. Time will tell how this all pans out. But I think what is even more interesting is the de-escalation question, and I think that is where tumor informed assays like Signatera and the data that our study generated can be applied. Actually, our plan is to generate some prospective data in the lobular breast cancer population, and I have an ongoing study to do that, to really be able to tease out the early ctDNA dynamics as patients first start on endocrine therapy. So, this is patients who are newly diagnosed, they are just starting on their first-line endocrine therapy, and measure, with sensitive assays, measure ctDNA dynamics in the first few months of therapy. In those patients who have a really robust response, that is where I think we can really think about de-escalation. In the patients whose ctDNA goes to undetectable after just a few weeks of therapy with just an endocrine agent, they might not even need a CDK4/6 inhibitor in their first-line treatment. So, that is an area where we are very interested in our group, and I know that other groups are looking at this too, to try to de-escalate therapy in patients who clear their ctDNA early on. Dr. Rafeh Naqash: Thank you so much. Well, lots of questions, but at the same time, progress comes through questions asked, and your project is one of those which is asking an interesting question in a rarer cancer and perhaps will lead to subsequent improvement in how we monitor these individuals and how we escalate or de-escalate therapy. Hopefully, we will get to see more of what you are working on in subsequent submissions to JCO Precision Oncology and perhaps talk more about it in a couple of years and see how the space and field is moving. Thanks again for sharing your insights. I do want to take one to two quick minutes talking about you as an investigator, Julia. If you could speak to your career pathway, your journey, the pathway to mentorship, the pathway to being a mentor, and how things have shaped for you in your personal professional growth. Dr. Julia Foldi: Sure, yeah, that is great. Thank you. So, I had a little bit of an unconventional path to clinical medicine. I actually thought I was going to be a basic scientist when I first started out. I got a PhD in Immunology right out of college and was studying not even anything cancer-related. I was studying macrophage signaling in inflammatory diseases, but I was in New York City. This was right around the time that the first checkpoint inhibitors were approved. Actually, some of my friends from my PhD program worked in Jim Allison's lab, who was the basic scientist responsible for ipilimumab. So, I got to kind of first-hand experience the excitement around bringing something from the lab into the clinic that actually changed really the course of oncology. And so, I got very excited about oncology and clinical medicine. So, I decided to kind of switch gears from there and I went back to medical school after finishing my PhD and got my MD at NYU. I knew I wanted to do oncology, so I did a research track residency and fellowship combined at Yale. I started working early on with the breast cancer team there. At the time, Lajos Pusztai was the head of translational research there at Yale, and I started working with him early in my residency and then through my fellowship. I worked on several trials with him, including a neoadjuvant checkpoint inhibitor trial in triple-negative breast cancer patients. During my last year in fellowship, I received a Conquer Cancer Young Investigator Award to study estrogen receptor heterogeneity using spatial transcriptomics in this subset of breast cancers that have intermediate estrogen receptor expression. From there, I joined the faculty at the University of Pittsburgh in 2022. So, I have been there about almost four years at this point. My interests really shifted slowly from triple-negative breast cancers towards ER-positive breast cancers. When I arrived in Pittsburgh, I started working very closely with some basic and translational researchers here who are very interested in estrogen signaling and mechanisms of resistance to endocrine therapy, and there is a large group here interested in lobular breast cancers. During my training, I was not super aware even that lobular breast cancer was a unique subtype of breast cancers, and that is, I think, changing a little bit. There is a lot more awareness in the breast cancer clinical and research community about ILC being a unique subtype, but it is not even really part of our training in fellowship, which we are trying to change. But I have become a lot more aware of this because of the research team here and through that, I have become really interested also on the clinical side. And so, we do have a Lobular Breast Cancer Research Center of Excellence here at the University of Pittsburgh and UPMC, and I am the leader on the clinical side. We have a really great team of basic and translational researchers looking at different aspects of lobular breast cancers, and some of the work that I am doing is related to this particular manuscript we discussed and the next steps, as I mentioned, a prospective study of early ctDNA dynamics in lobular patients. I also did some more clinical research work in collaboration with the NSABP looking at long-term outcomes of patients with lobular versus ductal breast cancers in some of their older trials. And so, that is, in a nutshell, a little bit about how I got here and how I became interested in ILC. Dr. Rafeh Naqash: Well, thank you for sharing those personal insights and personal journey. I am sure it will inspire other trainees, fellows, and perhaps junior faculty in trying to find their niche. The path, as you mentioned, is not always straight; it often tends to be convoluted. And then finding an area that you are interested in, taking things forward, and being persistent is often what matters. Dr. Julia Foldi: Thank you so much for having me. It was great. Dr. Rafeh Naqash: It was great chatting with you. And 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/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
In this episode of the Oncology Brothers podcast, hosts Rahul and Rohit Gosain dived deep into the evolving landscape of breast cancer treatment algorithms, focusing on early and locally advanced hormone receptor-positive breast cancer. Joined by Dr. Erica Mayer, a breast medical oncologist at the Dana-Farber Cancer Institute. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: • YouTube: https://www.youtube.com/@oncologybrothers/ • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ The discussion covered: • The role of chemotherapy in early-stage hormone receptor-positive breast cancer, including the use of anthracyclines versus taxane-based approaches. • Insights from the TAILORx trial and the implications of Oncotype DX scores in treatment decisions. • The ongoing OFSET trial and its potential impact on premenopausal patients with low recurrence scores. • The use of CDK4/6 inhibitors, including ribociclib and abemaciclib, in the adjuvant setting, along with their side effect profiles and dosing considerations. • The significance of the recent lidERA trial results featuring giredestrant and its implications for future treatment strategies. Join us as we explore the latest data, treatment paradigms, and the importance of patient-shared decision-making in breast cancer care. Don't forget to subscribe for more insights and staying up to date in the field of cancer. #EarlyBreastCancer, #OncotypeDX, #CDK46inhibitors, #OralSERD, #AdjuvantTherapy, #OncologyBrothers
In today's episode, our 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 our exclusive interview, Dr Bardia discussed key findings from the phase 3 lidERA Breast Cancer study (NCT04961996) showing the invasive disease–free survival superiority of giredestrant (GDC-9545) over standard endocrine therapy in patients with estrogen receptor–positive, HER2-negative early breast cancer. Our discussion also covered the ongoing phase 3 INAVO123 trial (NCT06790693), which is investigating inavolisib (Itovebi) plus CDK4/6 inhibitors and letrozole in patients with endocrine-sensitive, PIK3CA-mutated breast cancer. Dr Bardia also emphasized the importance of testing for ESR1 and PIK3CA mutations in order to better personalize treatment.
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/CTJ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 6, 2027.Key Steps to Success With CDK4/6 Inhibition in Early Through Metastatic Breast Cancer: Stratification, Selection, Sequencing, and Specialty Management 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 educational grants from Lilly and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/CTJ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 6, 2027.Key Steps to Success With CDK4/6 Inhibition in Early Through Metastatic Breast Cancer: Stratification, Selection, Sequencing, and Specialty Management 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 educational grants from Lilly and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.
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
Iaaaago Jorge convida Raphael Barreto e Lucas Brandão para discutir sobre neutropenia febril, em 5 clinicagens:1. Neutropenia febril é emergência oncológica2. Como escolher o antibiótico?3. Quando escalonar o antibiótico?4. Quando suspender o antibiótico?5. Quando prescrever filgrastim?Referências:1. Klastersky J, de Naurois J, Rolston K, et al. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016;27(suppl 5):v111-v118. doi:10.1093/annonc/mdw3252. Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol. 2018;36(14):1443-1453. doi:10.1200/JCO.2017.77.62113. Zhang H, Wu Y, Lin Z, et al. Naproxen for the treatment of neoplastic fever: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2019;98(22):e15840. doi:10.1097/MD.00000000000158404. Zheng B, Huang Z, Huang Y, Hong L, Li J, Wu J. Predictive value of monocytes and lymphocytes for short-term neutrophil changes in chemotherapy-induced severe neutropenia in solid tumors. Support Care Cancer. 2020;28(3):1289-1294. doi:10.1007/s00520-019-04946-35. Douglas C, Morse JD, Anderson BJ. Mucositis Pain and Its Temporal Relationship to White Cell Count. Paediatr Anaesth. 2025;35(4):302-309. doi:10.1111/pan.150636. Vassallo M, Michelangeli C, Fabre R, et al. Procalcitonin and C-Reactive Protein/Procalcitonin Ratio as Markers of Infection in Patients With Solid Tumors. Front Med (Lausanne). 2021;8:627967. Published 2021 Mar 12. doi:10.3389/fmed.2021.6279677. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33(28):3199-3212. doi:10.1200/JCO.2015.62.34888. Heil G, Hoelzer D, Sanz MA, et al. A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group. Blood. 1997;90(12):4710-4718.9. Weiss JM, Csoszi T, Maglakelidze M, et al. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019;30(10):1613-1621. doi:10.1093/annonc/mdz27810. Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64(2):328-340. doi:10.7326/0003-4819-64-2-32811. Nucci M, Arrais-Rodrigues C, Bergamasco MD, et al. Management of febrile neutropenia: consensus of the Brazilian Association of Hematology, Blood Transfusion and Cell Therapy - ABHH. Hematol Transfus Cell Ther. 2024;46 Suppl 6(Suppl 6):S346-S361. doi:10.1016/j.htct.2024.11.11912. Guarana M, Nucci M, Nouér SA. Shock and Early Death in Hematologic Patients with Febrile Neutropenia. Antimicrob Agents Chemother. 2019;63(11):e01250-19. Published 2019 Oct 22. doi:10.1128/AAC.01250-1913. Rosa RG, Goldani LZ. Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother. 2014;58(7):3799-3803. doi:10.1128/AAC.02561-1414. Averbuch D, Orasch C, Cordonnier C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013;98(12):1826-1835. doi:10.3324/haematol.2013.09102515. Beyar-Katz O, Dickstein Y, Borok S, Vidal L, Leibovici L, Paul M. Empirical antibiotics targeting gram-positive bacteria for the treatment of febrile neutropenic patients with cancer. Cochrane Database Syst Rev. 2017;6(6):CD003914. Published 2017 Jun 3. doi:10.1002/14651858.CD003914.pub416. Puerta-Alcalde P, Cardozo C, Suárez-Lledó M, et al. Current time-to-positivity of blood cultures in febrile neutropenia: a tool to be used in stewardship de-escalation strategies. Clin Microbiol Infect. 2019;25(4):447-453. doi:10.1016/j.cmi.2018.07.02617. Ljungman P, Alain S, Chemaly RF, et al. Recommendations from the 10th European Conference on Infections in Leukaemia for the management of cytomegalovirus in patients after allogeneic haematopoietic cell transplantation and other T-cell-engaging therapies. Lancet Infect Dis. 2025;25(8):e451-e462. doi:10.1016/S1473-3099(25)00069-618. Maertens J, Lodewyck T, Donnelly JP, et al. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. Clin Infect Dis. 2023;76(4):674-682. doi:10.1093/cid/ciac62319. Aguilar-Guisado M, Espigado I, Martín-Peña A, et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017;4(12):e573-e583. doi:10.1016/S2352-3026(17)30211-9
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.
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
In this JCO Precision Oncology Article Insights episode, host Dr. Harold Nathan Tan summarizes "Palbociclib in Patients With Head and Neck Cancer and Other Tumors With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study" by Worden et al. TRANSCRIPT Harold Nathan Tan: Welcome to JCO Precision Oncology Article Insights, where we explore research that is reshaping our understanding of cancer therapeutics. I'm your host, Harold Nathan Tan, and today's episode centers on the TAPUR study, an analysis that confronts a long-standing assumption in molecular oncology: namely, whether CDKN2A alterations create a therapeutic vulnerability that can be exploited by CDK4/6 inhibition with palbociclib. CDKN2A is one of the most frequently altered tumor suppressors across solid tumors. Its importance lies in its production of two proteins, p16 and p14, which serve as guardians of cell cycle progression. p16 directly inhibits CDK4 and CDK6, preventing phosphorylation of the RB protein and therefore blocking entry into S phase, whereas p14 stabilizes p53 by counteracting MDM2, enabling cells to pause or die in response to oncogenic stress. When CDKN2A is lost or mutated, these dual checkpoints collapse. CDK4/6 activity becomes unchecked, RB remains phosphorylated and inactive, and p53-mediated surveillance is blunted from a mechanistic standpoint. This creates a possible dependency on CDK4/6 signaling that could, in principle, be therapeutically reversed by palbociclib. The TAPUR study is a prospective phase 2 basket study designed to evaluate whether FDA-approved targeted agents can meaningfully benefit patients with advanced treatment-refractory cancers harboring specific genomic alterations. In this analysis, patients were eligible for palbociclib if their tumors carried CDKN2A loss or mutation and retained RB activity. Two cohorts were examined: one consisting of head and neck cancers, and another composed of a broad spectrum of tumor types that collectively shared the CDK2 alteration. The results from the head and neck cancer cohort are particularly intriguing. Among the 28 available patients, the study observed a disease control rate of 40%, surpassing the predefined threshold for a positive signal. Although the objective response rate was low at only 4% with one partial response, the durability of disease stabilization was clinically meaningful. However, the most important insight comes from examining which head and neck tumors benefited. The strongest and most durable disease control occurred in non-squamous malignancies, particularly salivary gland tumors such as adenocarcinoma, adenoid cystic carcinoma, and poorly differentiated parotid tumors, as well as in esthesioneuroblastoma. In contrast, classic head and neck squamous cell carcinoma rarely demonstrated sustained benefit. When progression-free survival was analyzed, non-squamous tumors achieved a median PFS of approximately 20 weeks compared to just eight weeks in squamous tumors. This divergence reflects deep biological differences. Many non-squamous head and neck cancers preserve an intact RB axis and rely on CDK4/6-driven cell cycle control as a core proliferative mechanism. By contrast, squamous tumors tend to accumulate a dense array of co-alterations that weaken or circumvent CDK4/6 dependency. Many squamous tumors also harbor disruptive TP53 mutations, removing essential checkpoint control and allowing the cell to bypass the growth-arresting effects of palbociclib. In other words, even though CDKN2A loss is present, CDK4/6 is no longer the dominant node controlling proliferation in these cancers, and the tumor simply finds other ways to drive cell cycle entry. One of the most thought-provoking findings from the TAPUR study involves esthesioneuroblastoma. Three patients with this rare tumor achieved durable disease control despite the lack of standardized systemic treatment options for this malignancy. Genomic analyses have shown that while esthesioneuroblastoma often carries TP53 or IDH2 mutations, a meaningful subset exhibits alterations in CDKN2A or related cell cycle regulators. The consistency of this disease stabilization observed in TAPUR may reflect a lineage-specific reliance on CDK4/6 signaling, opening the door for future exploration of CDK4/6 inhibitors in this orphan disease. In the histology-pooled cohort, which included 40 available patients across 18 tumor types, palbociclib did not achieve the disease control threshold required to declare activity, with only a disease control rate of 13% and an ORR of 5%. While a few isolated responses occurred, for instance in thymic carcinoma and B-cell lymphoma, the overall disease control rate was 13%, which failed to rise above what might be expected from the natural history of advanced refractory cancers. This outcome reinforces the principle that CDKN2A loss is not a universal predictor of CDK4/6 dependency. Many of the tumors represented in this cohort, such as pancreatic cancer, melanoma, and gastrointestinal malignancies, are well known to evolve multiple compensatory mechanisms that circumvent CDK4/6 as a critical proliferative node. The safety profile of palbociclib was consistent with its known hematologic toxicities. High rates of neutropenia, leukopenia, and thrombocytopenia were observed, along with one treatment-related death due to respiratory failure. In a setting where activity is limited to specific subgroups, these toxicities underscore the importance of careful patient selection and raise the bar for demonstrating clinically meaningful benefit, particularly in heavily pretreated populations. So what do these findings tell us about the broader landscape of precision oncology? First, they remind us that a mutation's functional role is dependent on the cellular and lineage context in which it occurs. CDKN2A loss may accelerate proliferation in many tumors, but the mechanism of that acceleration varies widely, and the degree to which a tumor relies on CDK4/6 signaling is anything but uniform. Second, the findings suggest that palbociclib monotherapy may hold meaningful and durable benefit in the subset of non-squamous head and neck cancers, particularly salivary gland malignancies and esthesioneuroblastoma. Third and perhaps most importantly, the results reinforce a growing consensus that the future of CDK4/6 inhibition in solid tumors lies not in monotherapy, but in rational combination strategies. CDK4/6 inhibitors have been shown to synergize with EGFR inhibitors, PIK3CA, and mTOR inhibitors, MEK inhibition, and even immune checkpoint blockade. These combinations aim to dismantle the compensatory pathways that allow tumors to escape CDK4/6 blockade and may unlock therapeutic potential in tumors that show limited sensitivity to monotherapy. Ultimately, the TAPUR findings challenge the notion that CDKN2A is a straightforward predictive biomarker. Instead, the study reveals CDKN2A as a biomarker whose meaning is modulated by tumor lineage, co-mutation status, and the broader regulatory circuit governing proliferation. Precision oncology must therefore move beyond single-gene interpretation towards integrated frameworks that situate genomic alterations within their biologic ecosystems. In some head and neck cancer subtypes, particularly non-squamous malignancies, that ecosystem appears amenable to CDK4/6 inhibition, and that insight, not the simplistic gene-to-drug match, represents the true value of the TAPUR analysis. Thank you for joining me for this episode of JCO Precision Oncology Article Insights. I'm Harold Nathan Tan, and I look forward to exploring more research that continues to refine how we understand and strategically exploit the vulnerabilities of cancer. 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.
Welcome to the Oncology Brothers podcast! In this episode, we dived into the key highlights from the SABCS 2025 conference, focusing on metastatic hormone receptor-positive breast cancer. Join us as we discussed: • The role of CDK4-6 inhibitors in frontline therapy, featuring updates from the AMBRE and MONALEESA-3 studies • Insights into second-line treatment options, including the VIKTORIA-1, evERA, EMBER-3, SERENA-6 trials • A critical look at the ASCENT-07 study, exploring the role of antibody-drug conjugates (ADCs) in endocrine-resistant disease We were thrilled to have Dr. Hope Rugo, a world-renowned breast medical oncologist from City of Hope, share her expertise and insights on these pivotal studies. Tune in for an informative discussion that unpacks the latest advancements in treatment options for metastatic hormone receptor-positive breast cancer, and learn how these findings may impact clinical practice. 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 #MBC #HRpositive #CDK46 #ADCs #OncologyBrothers
After surgery, many people with stage I to stage III hormone receptor-positive breast cancer take tamoxifen or an aromatase inhibitor for five to 10 years. This has been the standard of care for the last 25 years. At the 2025 San Antonio Breast Cancer Symposium, UCLA scientist Dr. Aditya Bardia presented results on giredestrant, a new oral selective estrogen degrader/downregulator (SERD) that offered better disease-free survival — how long people live without the cancer returning – than tamoxifen or an aromatase inhibitor. Listen to the episode to hear Dr. Bardia explain: how giredestrant is different from the two other available SERDs if giredestrant could be combined with a CDK4/6 inhibitor giredestrant side effects what the results mean for people diagnosed with early-stage hormone receptor-positive breast cancer
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/DTQ865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until November 25, 2026.Nurturing Lasting Benefits of Adjuvant CDK4/6 Inhibitor Therapy in High-Risk HR+, HER2- EBC: Best Practices for Patient Education, AE Monitoring and Management, and Enhanced Adherence/Persistence 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 Lilly.Disclosure information is available at the beginning of the video presentation.
Featuring an interview with Dr Priyanka Sharma, including the following topics: Patient-reported outcomes from the SERENA-6 trial of camizestrant with a CDK4/6 inhibitor for patients with HR-positive, HER2-negative advanced breast cancer and ESR1 mutations emerging during first-line endocrine-based therapy (0:00) Mayer E et al. Patient-reported outcomes (PROs) from the SERENA-6 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1m during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC). ESMO 2025;Abstract 486MO. Imlunestrant and abemaciclib versus fulvestrant and abemaciclib for ER-positive, HER2-negative advanced breast cancer: An indirect treatment comparison of 3 Phase III trials (3:00) Bidard FC et al. Imlunestrant plus abemaciclib versus fulvestrant plus abemaciclib in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): An indirect treatment comparison (ITC) of three phase 3 trials. ESMO 2025;Abstract 496P . Giredestrant in the treatment of ER-positive, HER2-negative breast cancer: The Phase III evERA Breast Cancer and EMPRESS trials (5:39) Mayer E et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial. ESMO 2025;Abstract LBA16. Llombart-Cussac A et al. Preoperative window-of-opportunity study with giredestrant or tamoxifen (tam) in premenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) and Ki67≥10% early breast cancer (EBC): The EMPRESS study. ESMO 2025;Abstract 294MO. Capivasertib/fulvestrant as first- and second-line endocrine-based therapy for PIK3CA/AKT1/PTEN-altered HR-positive advanced breast cancer in the CAPItello-291 trial and gedatolisib/fulvestrant with or without palbociclib for HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer in the VIKTORIA-1 trial.(10:25) Rugo HS et al. Capivasertib plus fulvestrant as first and second-line endocrine-based therapy in PIK3CA/AKT1/PTEN-altered hormone receptor-positive advanced breast cancer: Subgroup analysis from the phase 3 CAPItello-291 trial. ESMO 2025;Abstract 526P. Hurvitz SA et al. Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): First results from VIKTORIA-1. ESMO 2025;Abstract LBA17. CME information and select publications
Did you know that the prevalence of acquired ESR1 mutations increases after exposure to endocrine therapy? Credit available for this activity expires: 11/26/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/advancing-copd-care-through-precision-medicine-and-patient-2025a1000x00?ecd=bdc_podcast_libsyn_mscpedu
In this episode of the Oncology Brothers podcast, we took a deeper dive into the evolving landscape of CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer. Joined by esteemed oncologists Dr. Sara Tolaney from Dana-Farber Cancer Institute and Dr. Adam Brufsky from UPMC Hillman Cancer Center, the discussion focused on real-world scenarios involving adjuvant and metastatic settings. Key topics included: • The recent updates from the MonarchE and NATALEE trials, highlighting the approval of abemaciclib and ribociclib. • Strategies for selecting the right adjuvant treatment for high-risk patients, including dosing considerations and side effect management. • Insights into managing common toxicities associated with CDK4/6 inhibitors, such as diarrhea and QTc prolongation. • The role of CDK4/6 inhibitors in patients with visceral involvement and the implications of using these therapies in the metastatic setting. Whether you're a healthcare professional or someone interested in the latest advancements in breast cancer treatment, this episode provided valuable insights and expert opinions on navigating complex treatment decisions. 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 send us your challenging cases for future discussions! #CDK4/6i #BreastCancer #MonarchE #NATALEE #Abemaciclib #Ribociclib #OncologyBrothers #HRpositive
Featuring a slide presentation and related discussion from Dr Erika Hamilton, including the following topics: Mechanisms of endocrine resistance; incidence of ESR1 mutations in breast cancer (0:00) Testing methods for ESR1 mutations in patients with breast cancer; therapeutic options for patients with ESR1-mutant breast cancer (3:59) General overview of proteolysis-targeting chimeras (PROTACs); comparison of PROTAC estrogen receptor (ER) degraders and selective ER degraders (7:39) Early-phase data with vepdegestrant monotherapy or in combination with CDK4/6 inhibitors in ER-positive, HER2-negative metastatic breast cancer (mBC) (11:54) Phase III VERITAC-2 trial of vepdegestrant versus fulvestrant in ER-positive, HER2-negative mBC previously treated with endocrine therapy and a CDK4/6 inhibitor (17:48) Ongoing clinical trials evaluating vepdegestrant in novel combinations or treatment settings; other clinical applications of PROTACs (26:08) CME information and select publications
In today's episode, we had the pleasure of speaking with Kevin Kalinsky, MD, MS, FASCO, about the evolving treatment paradigm for hormone receptor (HR)–positive breast cancer post-CDK4/6 inhibition, as well as the need for more advanced therapies to improve patient outcomes in this setting. Dr Kalinsky is a professor and director in the Division of Medical Oncology of the Department of Hematology and Medical Oncology at Emory University School of Medicine, as well as the director of the Glenn Family Breast Center and the Louisa and Rand Glenn Family Chair in Breast Cancer Research at Winship Cancer Institute in Atlanta, Georgia. In our exclusive interview, Dr Kalinsky discussed combination therapies that have shown promise for the management of HR-positive breast cancer following endocrine therapy, factors influencing treatment selection for patients who have received prior CDK4/6 inhibition, best practices for genomic testing in this population, and breast cancer research highlights from the 2025 ESMO Congress.
Drs. Waks and Lynce review the PATINA trial, which showed that adding a CDK4/6 inhibitor to HER2-targeted and endocrine therapy improved progression-free survival in triple-positive breast cancer, shaping how this subgroup may be managed.
In this episode of Oncology Brothers, we dived deep into the world of CDK4-6 inhibitors, focusing on their side effects and management in breast cancer treatment. Joined by an esteemed guest, Dr. Stephanie Graff, a medical breast oncologist from Brown University Health. We explored the side effects and management strategies for three commonly used CDK4/6 inhibitors: ribociclib, abemaciclib, and palbociclib. Key topics discussed include: • The evolving role of CDK4/6 inhibitors in early breast cancer and adjuvant settings. • Detailed management of side effects such as QT prolongation, liver function tests, and diarrhea. • The importance of shared decision-making with patients regarding treatment options. • Insights into the latest clinical trial data and its implications for practice. Whether you're a healthcare professional or someone interested in oncology, this episode provides valuable insights into optimizing patient care while managing the complexities of CDK4-6 inhibitors. 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 discussions on oncology treatments and patient management strategies! #CDK4/6inhibitors #BreastCancer #Ribociclib #Abemaciclib #Palbociclib #OncologyBrothers #SideEffectManagement #HRpositiveBC
The George Washington Cancer Center serves a racially, ethnically, and socioeconomically diverse population across Washington, D.C., northern Virginia, and southern Maryland. Their Breast Cancer Program has found that a community-informed model is most successful for managing care and adverse events related to CDK4/6 inhibitors. In this episode, CANCER BUZZ speaks with Pavani Chalasani, MD, MPH, director of the division of hematology/oncology at the George Washington University Cancer Center about the flexible and collaborative team design that allows for culturally responsive and comprehensive care for their patients with breast cancer. Pavani Chalasani, MD, MPH Director, Division of Hematology/Oncology George Washington University Cancer Center Washington, DC “I think adapting and knowing what the barriers are and how we can divide and support and come up with roles for our team members is essential.” “[Navigators] give us an understanding of where the hesitancy is coming from, or where the concerns are coming from, so that we can do a better job explaining and overcoming those barriers.” Resources · Spotlight on George Washington (GW) Cancer Center: Managing Adverse Effects of CDK4/6 Inhibitors With a Patient-Centered, Team-Based Approach · ACCC Resource: CDK4/6 Inhibitors Management · ACCC CDK4/6 Inhibitors Infographic
Dr. Virginia Kaklamani, world renowned breast cancer specialist and researcher, visits with Healthcare Unfiltered EXPRESS to detail how this class of agents are used in metastatic and early stage breast cancer. A perfect guide for all clinicians.
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