Ciruelos EM, Rugo HS, Mayer IA, et al. - The phase 3 SOLAR-1 trial demonstrated significant improvement in median progression-free survival in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)–mutated, hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer in correlation with the PI3Kα-selective inhibitor and degrader alpelisib added to fulvestrant. Researchers here sought to report on health-related quality of life utilizing patient-reported outcome measures in these patients. In the PIK3CA-mutant cohort, random assignment of 341 patients in a 1:1 ratio was done to alpelisib 300 mg daily or placebo plus fulvestrant 500 mg on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Per outcomes, the arms exhibit no statistical difference between them in deterioration of Global Health Status/QoL in SOLAR-1, whereas placebo was favored by symptom subscales for diarrhea, appetite loss, nausea or vomiting, and fatigue, known side effects of alpelisib. They highlight that consideration must be given to efficacy and tolerability in treatment decisions; taken with clinical efficacy, these outcomes yield support for the benefit-risk profile of alpelisib in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative PIK3CA-mutated advanced breast cancer.