On May 24, the U.S. Food and Drug Administration (FDA) approved the PIK3CA inhibitor alpelisib (Piqray) tablets to be used in combination with the FDA-approved endocrine therapy fulvestrant to treat postmenopausal women and men with hormone receptor–positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer (as detected by an FDA-approved test) following disease progression on or after an endocrine-based regimen. Approval was based on the results of the SOLAR-1 trial.
The FDA also approved the companion diagnostic therascreen PIK3CA RGQ PCR Kit to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who tested negative on the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.
In the double-blind trial, 572 patients were enrolled into two cohorts on the basis of tumor-tissue PIK3CA mutation status. Patients were then randomly assigned to receive alpelisib at 300 mg/d plus fulvestrant at 500 mg every 28 days and once on day 15 or placebo plus fulvestrant. In the cohort with -PIK3CA-mutated cancer, 169 patients received treatment with alpelisib/fulvestrant and 172 received placebo/fulvestrant; in the cohort without PIK3CA mutation, 115 received alpelisib/fulvestrant and 116 received placebo/fulvestrant.
The median follow-up was 20 months. Among the 341 patients with PIK3CA mutations, the median progression-free survival was 11.0 months with alpelisib vs 5.7 months with placebo (hazard ratio [HR] = 0.65, P < .001). In this cohort, the overall response rate was 26.6% vs 12.8%. In the cohort of 231 patients without PIK3CA mutation, the median progression-free survival was 7.4 months vs 5.6 months (HR = 0.85).