Insights

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 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.

Benjamin P. Levy, MD, and Misty D. Shields, MD, PhD, discuss Bridging the Gaps in lung cancer, a collection and review of updated data from the Winter Lung Cancer Conference 2025, that was significant to their practice and future implications of data across 6 key areas, including small cell lung cancer, perioperative treatment strategies in non–small cell lung cancer (NSCLC), advancements in unresectable early-stage NSCLC, treatment strategies for EGFR-mutated NSCLC, targeting ALK/ROS1/HER2/NRG1 mutations in NSCLC, and immunotherapy in advanced NSCLC.

Heather Wakelee, MD, FASCO, and Roy S. Herbst, MD, PhD, discuss how recent clinical trials demonstrate superior outcomes with combination therapies over single-agent osimertinib in EGFR-positive NSCLC, while highlighting the need for careful toxicity management and continued research to address treatment resistance.

Expert discussions on the latest advances in biomarker testing, endocrine resistance, and treatment sequencing with oral SERDs and other emerging therapies to enhance outcomes in HR+/HER2- metastatic breast cancer.

Sandra D’Angelo, MD, and Nam Bui, MD, examine synovial sarcoma's distinct molecular signature driven by the SS18-SSX fusion gene, highlighting critical unmet treatment needs that led to the groundbreaking approval of afami-cel, a MAGE-A4-targeted TCR therapy demonstrating promising efficacy in the SPEARHEAD-1 trial, potentially paving the way for broader adoption of TCR-based therapies in solid tumors.

Panelists discuss how genetic testing and RET-targeted therapies play a crucial role in guiding the treatment of advanced NSCLC, with a focus on optimizing first-line therapy and managing challenges in molecular testing and treatment sequencing.

Jorge Cortes, MD, and Stephen A. Strickland Jr, MD, MSCI,discuss how in the management of chronic myeloid leukemia (CML), clinicians must carefully monitor early treatment response milestones with first-line tyrosine kinase inhibitor therapy, consider appropriate switching strategies including BCR::ABL1 mutation testing, and select between newer agents such as asciminib and ponatinib based on patient-specific factors, trial data, and distinct safety profiles, particularly regarding cardiovascular toxicities.

Panelists discuss how recent advancements in ovarian cancer treatment, including biomarker-guided therapy, PARP inhibitors, combination therapies, and antibody-drug conjugates, are shaping personalized management strategies to improve patient outcomes.