Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer.

Area of Science:

• Oncology
• Medical Research
• Pharmacology

Background:

• Approximately 40% of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer cases harbor PIK3CA mutations.
• Alpelisib, a PI3Kα-specific inhibitor, has demonstrated antitumor activity in preliminary studies.

Purpose of the Study:

• To evaluate the efficacy and safety of alpelisib plus fulvestrant compared to placebo plus fulvestrant in patients with HR-positive, HER2-negative advanced breast cancer.
• To assess the impact of PIK3CA mutation status on treatment outcomes.

Main Methods:

• A randomized, phase 3 trial (SOLAR-1) involving 572 patients with advanced HR-positive, HER2-negative breast cancer previously treated with endocrine therapy.
• Patients were stratified into two cohorts based on tumor-tissue PIK3CA mutation status.
• Primary endpoint: progression-free survival (PFS) in the PIK3CA-mutated cohort; secondary endpoints: PFS in the PIK3CA-wildtype cohort, overall response, and safety.

Main Results:

• In the PIK3CA-mutated cohort, alpelisib-fulvestrant significantly prolonged median PFS to 11.0 months versus 5.7 months with placebo-fulvestrant (hazard ratio [HR], 0.65; P<0.001).
• In the PIK3CA-wildtype cohort, the HR for progression or death was 0.85 (95% CI, 0.58 to 1.25), indicating less benefit.
• Grade 3/4 hyperglycemia and rash were the most frequent adverse events in the alpelisib-fulvestrant group.

Conclusions:

• Alpelisib plus fulvestrant demonstrated a significant improvement in progression-free survival for patients with PIK3CA-mutated, advanced HR-positive, HER2-negative breast cancer.
• The findings support alpelisib-fulvestrant as a targeted treatment option for this patient population.