HR-Positive/HER2-Negative Metastatic Breast Cancer: Managing PI3K-Directed Triplet Therapy and Treatment-Related Toxicities

Dr. Adam Brufsky and the panel discuss the practical implementation of PI3K-directed triplet therapy in patients with HR-positive/HER2-negative metastatic breast cancer, focusing on treatment selection, sequencing considerations, and toxicity management. The faculty explore scenarios involving patients with aggressive disease biology, prior CDK4/6 inhibitor exposure, and high-risk molecular features, emphasizing the need to balance efficacy with patient-specific clinical factors. Dr. Rebecca Shatsky, Dr. Rita Nanda, and Dr. Virginia Kaklamani review strategies for identifying appropriate candidates for triplet therapy and discuss situations in which chemotherapy or antibody-drug conjugates may be considered. A significant portion of the conversation focuses on proactive management of treatment-related adverse events, particularly hyperglycemia, stomatitis, rash, and diarrhea. The panel shares practical approaches to monitoring glucose levels, collaborating with endocrinology specialists, implementing supportive care measures, and educating patients on symptom management. The discussion highlights the importance of multidisciplinary care and careful toxicity monitoring to optimize outcomes while maintaining treatment adherence in patients receiving targeted combination therapies for HR-positive/HER2-negative metastatic breast cancer.