OncLive Insights

Komal Jhaveri, MD, FACP; and Kevin M. Kalinsky, MD, MS, discuss how emerging oral selective estrogen receptor degraders and proteolysis-targeting chimeras are transforming breast cancer treatment by providing new targeted options for ESR1-mutant tumors, the evolving role of CDK4/6 inhibitor sequencing strategies including molecular progression–based treatment switching, and the integration of antibody-drug conjugates across different breast cancer subtypes from later-line to first-line metastatic settings.

Panelists discuss how HER2 mutations in metastatic non–small cell lung cancer (mNSCLC) require comprehensive molecular testing including both next-generation sequencing and immunohistochemistry, and how the recent FDA approval of zongertinib as a HER2-specific tyrosine kinase inhibitor provides a new targeted therapy option with superior tolerability compared with trastuzumab deruxtecan, emphasizing the importance of proper treatment sequencing and the evolving landscape from chemotherapy-based approaches to precision medicine in this patient population.

Panelists explore treatment strategies and the integral role of the multidisciplinary care team in optimizing outcomes in CML.

Experts discuss the evolving treatment landscape of pediatric low-grade glioma (pLGG), including molecular testing, frontline and relapsed therapy strategies, multidisciplinary decision-making, and real-world case applications to optimize personalized care.

John Allan, MD; Susan O’Brien, MD; and Javier Pinilla, MD, PhD, discuss how shared decision-making in chronic lymphocytic leukemia (CLL) treatment involves balancing Bruton tyrosine kinase (BTK) inhibitor safety profiles, efficacy data, and patient preferences when choosing among continuous monotherapy, fixed-duration combinations, and managing treatment-related adverse events through dose modifications and multidisciplinary care approaches.

Peter Voorhees, MD and Louis Williams, MD discuss how CAR T-cell therapy eligibility assessment, optimal timing for earlier-line treatment, long-term efficacy data from CARTITUDE studies, and emerging next-generation CAR T products are reshaping the treatment landscape for relapsed/refractory multiple myeloma patients.

Julia Foldi, MD, PhD; Elisa Krill-Jackson, MD; and Timothy J. Pluard, MD, discuss how the INAVO120 trial’s final overall survival (OS) analysis demonstrates a significant 7-month median OS benefit (34 vs 27 months) with inavolisib plus palbociclib plus fulvestrant in PIK3CA-mutated endocrine-resistant metastatic breast cancer, though the limited crossover rate (< 10%) to PIK3CA inhibitors in the control arm complicates interpretation of optimal sequencing strategies.

Paul E. Oberstein, MD; Priyadarshini Pathak, MBBS; and Tara E. Seery, MD, discuss how to optimize treatment decisions for patients with pancreatic cancer by comparing NALIRIFOX vs modified FOLFIRINOX regimens, sequencing therapies from first to second line, managing toxicities through dose modifications to maintain patients on treatment longer, and the promising pipeline of emerging targeted therapies including KRAS inhibitors and immunotherapy combinations presented at ASCO 2025.

Sandip P. Patel, MD; Zofia Piotrowska, MD, MHS; and Joel Neal, MD, PhD, discuss how the evolving landscape of EGFR-mutated non–small cell lung cancer treatment now includes 3 compelling frontline options (osimertinib monotherapy, FLAURA2 regimen, and MARIPOSA), requiring careful consideration of patient factors, disease characteristics, and toxicity profiles for optimal treatment selection and sequencing strategies.

Panelists discuss RAS mutations in pancreatic cancer, focusing on prevalence and testing, evolving second-line treatment strategies including emerging targeted agents like daraxonrasib, and key ASCO 2025 highlights and future perspectives in pancreatic ductal adenocarcinoma (PDAC).

Jason A. Mouabbi, MD, discusses how ESR1 mutations should be monitored after each progression in hormone receptor-positive breast cancer patients and treated with elacestrant, emphasizing the importance of liquid biopsies for detection and the promising results from studies like SERENA-6 that suggest switching therapy early based on molecular progression rather than waiting for radiological evidence.

Joshua Sabari, MD and Isabel Preeshagul, DO, MBS, discuss how comprehensive biomarker testing for HER2 mutations in non–small cell lung cancer (NSCLC) enables targeted treatment with emerging therapies including antibody-drug conjugates such as trastuzumab deruxtecan and promising oral tyrosine kinase inhibitors such as zongertinib and sevabertinib, which offer improved tolerability and central nervous system penetration compared with traditional chemotherapy approaches.

Panelists discuss how comprehensive biomarker testing informs patient selection for antibody-drug conjugate (ADC) therapy in HER2+ ovarian and endometrial cancers, while evaluating ADC positioning in the evolving gynecologic oncology landscape, comparing structural components that influence efficacy and safety, and outlining strategies for monitoring and managing emerging ADC toxicities.

Catherine Coombs, MD; John Allan, MD; and Joanna Rhodes, MD, MSCE, discuss how to treat patients with chronic lymphocytic leukemia (CLL) who develop high-risk disease features at relapse after initial venetoclax-based therapy. They cover treatment sequencing strategies, Bruton tyrosine kinase (BTK) inhibitor tolerability issues and switching approaches, retreatment considerations, and emerging therapies including chimeric antigen receptor (CAR) T-cell therapy and novel agents in development.

Panelists discuss the expanding treatment landscape for neuroendocrine tumors.

Panelists discuss the treatment of relapsed and refractory multiple myeloma, as well as sequencing strategies aimed at optimizing patient care and minimizing treatment-related side effects,presenting two real-world patient cases and explain our treatment approach, highlighting how they incorporate recent data into our practice.

Kelly E. McCann, MD, PhD; and Gregory Vidal, MD, PhD, discuss how triple-positive breast cancer (hormone receptor positive and HER2 positive) requires specialized treatment approaches, including standard taxane with pertuzumab-trastuzumab combinations, the integration of CDK 4/6 inhibitors, considerations for ovarian suppression in premenopausal patients, and sequential therapy options for metastatic disease including antibody-drug conjugates and tyrosine kinase inhibitors.

Zosia Piotrowska, MD, MHS, and Martin Dietrich, MD, PhD, discuss how the treatment landscape for EGFR-mutated non–small cell lung cancer (NSCLC) has evolved from osimertinib monotherapy toward combination approaches, with experts weighing efficacy benefits against toxicity profiles while emphasizing the importance of individualized treatment selection, prophylactic toxicity management, and careful consideration of subsequent therapy options after disease progression.

Panelists discuss how immune-oncology therapies and biomarkers like TMB, MSI, and HER2 are shaping treatment strategies and decision-making in advanced endometrial cancer, highlighting the need for further research and improved sequencing approaches.

Experts discuss the latest clinical data on tyrosine kinase inhibitor (TKI) therapy for gastrointestinal stromal tumors (GIST), focusing on optimizing treatment selection and sequencing strategies for patients progressing beyond first-line therapy, with insights into how molecular characterization and recent clinical trials inform decisions across multiple treatment lines, illustrated through patient case discussions.

Experts explore the growing role of CAR T-cell therapy in the treatment of r/r MM, as well as dive into recent data updates, importance of early referral, and future directions of CAR-T in this rapidly evolving field.

Christine M. Lovly, MD, PhD, FASCO; and Balazs Halmos, MD, MS, discuss how the first-line treatment landscape for EGFR-mutated non–small cell lung cancer (NSCLC) is evolving, with osimertinib as the standard, while combinations are explored to enhance efficacy. FLAURA, FLAURA2, and MARIPOSA trials inform treatment selection, balancing efficacy, safety, and CNS activity. Patient factors such as disease burden and resistance guide sequencing decisions, with MARIPOSA-2 and PALOMA-3 shaping second-line choices. Managing adverse events in combination regimens remains key. Unmet needs include overcoming resistance and improving long-term outcomes.

Experts examine recent updates in diffuse large B-cell lymphoma (DLBCL) treatment and explore practical strategies for implementing chimeric antigen receptor (CAR) T-cell therapy through academic and community collaboration.

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Experts explore the evolving role of chimeric antigen receptor (CAR) T-cell therapy in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), with a focus on patient selection, recent data updates, and sequencing strategies.

Julia Rotow, MD and Edgardo S. Santos Castillero, MD, FACP, FASCO, discuss how, when selecting frontline therapy for EGFR-mutated non–small cell lung cancer (NSCLC), key considerations include central nervous system involvement, metastases, and mutational factors like TP53. Shared decision-making prioritizes progression-free survival, toxicity, and convenience. Future therapy sequencing, evolving MARIPOSA data, and novel agents shape treatment strategies while balancing efficacy and tolerability.