Pathway-Directed Treatment in PIK3CA-Mutated HR+/HER2-Negative Advanced Breast Cancer

Dr. Jason Mouabbi discusses how available pathway-directed treatment approaches may be differentiated for patients with biomarker-selected HR-positive/HER2-negative advanced breast cancer, with consideration of treatment setting and toxicity profiles. He contrasts the first-line treatment approach evaluated in INAVO120 with established pathway-directed options used after progression on initial therapy, including alpelisib plus fulvestrant and capivasertib plus fulvestrant. Dr. Mouabbi highlights differences in the adverse-event profiles of these agents, noting greater emphasis on hyperglycemia and rash with alpelisib and diarrhea with capivasertib. He also discusses emerging pathway-directed treatment with gedatolisib and explains its current biomarker-defined treatment setting, while noting that data in PIK3CA-mutated disease may inform future treatment considerations. The discussion emphasizes that pathway-directed therapies can share overlapping toxicity categories, including hyperglycemia, diarrhea, stomatitis, and rash, while individual agents may have different toxicity patterns. Treatment setting, biomarker status, route and schedule of administration, and anticipated toxicities are considered when evaluating available approaches for individual patients.