Treatment Selection and Toxicity Counseling in HR+/HER2-Negative Advanced Breast Cancer

Dr. Paolo Tarantino discusses treatment selection for patients with hormone receptor-positive, HER2-negative advanced breast cancer harboring an activating AKT1 mutation. He identifies capivasertib, an AKT inhibitor, as a targeted treatment option supported by the phase 3 CAPItello-291 trial and contrasts it with other pathway-directed agents, including everolimus and investigational gedatolisib, which have not been specifically developed or established for this molecularly defined population. He emphasizes the importance of assessing baseline glucose status before initiating capivasertib, noting that the patient's HbA1c of 6.4%, despite indicating prediabetes, is below the 8% threshold used for eligibility in CAPItello-291. Dr. Tarantino discusses fulvestrant plus capivasertib as a potential treatment regimen and highlights the need for proactive patient education about adverse events. He reviews diarrhea as a common toxicity, recommending counseling on adequate hydration and access to loperamide, while also addressing the risks of rash and hyperglycemia, including the importance of preparing patients for potentially serious events.