- Adding the PI3Kα-specific inhibitor alpelisib to fulvestrant extends PFS in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer with PIK3CA mutations.
- Patients without PIK3CA mutations failed to benefit.
Why this matters
- PIK3CA mutations are common, affecting 40% of patients with HR+/HER2− advanced breast cancer.
- Alpelisib may become a new treatment option for patients with PIK3CA mutations.
- Randomized, phase 3 SOLAR-1 trial (n=572) comparing fulvestrant (500 mg every 28 days and once on day 15) with alpelisib (oral dose of 300 mg/day) or placebo for advanced HR+/HER2− breast cancer in women and men previously treated with endocrine therapy.
- 2 cohorts were randomized: those with and without PIK3CA mutations.
- Funding: Novartis Pharmaceuticals.
- Cohort with PIK3CA mutations:
- The alpelisib group, at a median follow-up of 20.0 months, had longer PFS (11.0 vs 5.7 months in the placebo group), with adjustment (HR, 0.65; P<.001>
- Cohort without PIK3CA mutations:
- The alpelisib group had nonsignificantly longer PFS (7.4 vs 5.6 months, respectively), with adjustment (HR, 0.85; 95% CI, 0.58-1.25); posterior probability of true HR being
- Alpelisib-treated patients had a higher dropout rate (25.0% vs 4.2%), primarily as a result of hyperglycemia (6.3%) and rash (3.2%).
- High rate of dropouts in alpelisib recipients.