HR-Positive/HER2-Negative Metastatic Breast Cancer: Sequencing Strategies After CDK4/6 Inhibitor Progression

Dr. Adam Brufsky and the panel examine treatment decision-making following progression on first-line CDK4/6 inhibitor-based therapy in patients with HR-positive/HER2-negative metastatic breast cancer. The discussion begins with the management of oligoprogressive disease, including the potential roles of local therapy, continued CDK4/6 inhibition, endocrine therapy modification, and molecular testing. Dr. Rita Nanda, Dr. Rebecca Shatsky, and Dr. Virginia Kaklamani share perspectives on extending the benefit of endocrine-based treatment through individualized sequencing strategies while balancing symptom burden and disease progression. The faculty emphasize the importance of repeat genomic testing at progression to identify actionable alterations that may guide subsequent therapy selection. The conversation then shifts to treatment options for patients with PI3K pathway alterations and explores emerging therapies under clinical investigation. The panel discusses anticipated data from ASCO 2026, practical considerations related to efficacy, toxicity, route of administration, and patient quality of life, highlighting the ongoing challenges of optimizing sequencing strategies in HR-positive/HER2-negative metastatic breast cancer.