FDA Approves Alpelisib in Combination With Fulvestrant for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer


Key Points

  • In patients with PIK3CA-mutated disease, the addition of alpelisib to fulvestrant prolonged progression-free survival.
  • No significant benefit was observed among patients without PIK3CA-mutated disease.

On May 24, the U.S. Food and Drug Administration (FDA) approved alpelisib (Piqray) tablets to be used in combination with the FDA-approved endocrine therapy fulvestrant to treat postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer (as detected by an FDA-approved test) following progression on or after an endocrine-based regimen. The approval was based on results of the SOLAR-1 trial, results of which were recently reported by André et al in The New England Journal of Medicine.

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 are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

Study Details

In the double-blind trial, 572 patients from 198 sites in 34 countries were enrolled into two cohorts on the basis of tumor-tissue PIK3CA mutation status. Patients were then randomly assigned between July 2015 and July 2017 to receive alpelisib 300 mg per day plus fulvestrant 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 placebo/fulvestrant.

The primary endpoint was progression-free survival in the PIK3CA-mutated cohort.

Progression-Free Survival

Median follow-up was 20 months. Among the 341 patients with PIK3CA mutations, median progression-free survival was 11.0 months in the alpelisib group vs 5.7 months in the placebo group (hazard ratio [HR] = 0.65, P < .001). In this cohort, overall response rates were 26.6% vs 12.8% (35.7% vs 16.2% among those with measureable disease). In the cohort of 231 patients without PIK3CA mutation, median progression-free survival was 7.4 months vs 5.6 months (HR = 0.85, 95% confidence interval [CI] = 0.58–1.25).

Adverse Events

Among all patients, the most common grade 3 or 4 adverse events in the alpelisib group were hyperglycemia (36.6% vs 0.7% in the placebo group) and rash (9.9% vs 0.3%); grade 3 diarrhea occurred in 6.7% of patients in the alpelisib group vs 0.3% of the placebo group. Serious adverse events occurred in 34.9% vs 16.7% of patients. Alpelisib and placebo were discontinued due to adverse events in 25.0% vs 4.2% of patients, with the most common reasons in the alpelisib group being hyperglycemia (6.3%) and rash (3.2%).

The investigators concluded, “Treatment with alpelisib/fulvestrant prolonged progression-free survival among patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously.”

Commenting on the FDA approval, Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said, “[Alpelisib] is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer. The ability to target treatment to a patient’s specific genetic mutation or biomarker is becoming increasingly common in cancer treatment, and companion diagnostic tests assist oncologists in selecting patients who may benefit from these targeted treatments. For this approval, we employed some of our newer regulatory tools to streamline reviews without compromising the quality of our assessment. This drug is the first novel drug approved under the Real-Time Oncology Review pilot program. We also used the updated Assessment Aid, a multidisciplinary review template that helps focus our written review on critical thinking and consistency and reduces time spent on administrative tasks.”

Disclosure: The study was funded by Novartis Pharmaceuticals. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.