Final overall survival results of SOLAR-1 add to growing body of evidence for alpelisib

September 2020 Pharma News Jolien Blokken

After a significant improvement in progression-free survival, final overall survival (OS) results of the SOLAR-1 trial could now demonstrate that alpelisib plus fulvestrant induces a clinically relevant improvement of eight months in OS for patients with HR+/HER2- advanced breast cancer with a PIK3CA mutation, as compared to fulvestrant alone. To date, alpelisib represents the only treatment in Europe that is specifically approved for this patient population with poor prognosis.

About SOLAR-1

The SOLAR-1 trial, evaluated alpelisib in combination with fulvestrant, compared to fulvestrant alone, in hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer patients with tumours harbouring a PIK3CA mutation. All enrolled patients progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor. Based on central tumour tissue assessment, patients were allocated to a PIK3CA-mutated cohort (N= 341) or a PIK3CA non-mutated cohort (N= 231). Within each cohort, patients were randomised in a 1:1 ratio to receive continuous oral treatment with alpelisib (300 mg once daily) plus fulvestrant (500 mg on day 1 and day 15 of the first 28-day cycle, than day 1 of subsequent cycles) or placebo plus fulvestrant. Previously reported study results could demonstrate that SOLAR-1 met its primary endpoint of improved progression-free survival (PFS) in the PIK3CA-mutant cohort. Alpelisib together with fulvestrant nearly doubled PFS as compared to fulvestrant alone in the PIK3CA-mutant cohort (HR[95%CI]: 0.65[0.50-0.85], p< 0.001; median PFS 11.0 vs. 5.7 months).1 Based on these results, in July 2020, the European Commission approved alpelisib in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2- locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy. At ESMO 2020, the results of the final OS analysis of SOLAR-1 were presented.

Final overall survival analysis

After a median follow-up of 30.8 months, the median OS improved from 31.4 months with placebo + fulvestrant to 39.3 months with alpelisib + fulvestrant (HR[95%CI]: 0.86[0.64-1.15], p= 0.15). Although this difference did not reach the prespecified threshold of statistical significance set for the secondary objective of OS in patients with PIK3CA-mutated breast cancer, this represents a clinically relevant improvement of eight months. In addition, a median delay of 8.5 months in time to chemotherapy was observed for patients in the alpelisib plus fulvestrant arm as compared to the placebo plus fulvestrant arm (23.3 vs. 14.8 months, HR[95%CI]: 0.72[0.54-0.95]). Finally, an OS improvement of more than fourteen months was achieved in patients with lung or liver metastases, a more aggressive and challenging to treat group of patients (37.2 vs. 22.8 months, HR[95%CI]: 0.68[0.46-1.00]). No new safety signals were observed with longer follow-up.2


Although not statistically significant, the addition of alpelisib to fulvestrant resulted in a clinically relevant eight month improvement in overall survival for patients with HR+/HER2- PIK3CA-mutated advanced breast cancer. In addition, the median time to chemotherapy was also prolonged with alpelisib + fulvestrant as compared to placebo + fulvestrant. The statistically significant prolongation in PFS, previously observed in SOLAR-1, is thus supported by a numeric increase in OS.


  1. André F, Ciruelos EM, Rubovszky G, et al. Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): results of the Phase 3 SOLAR-1 trial. Presented at ESMO 2018; Abstract LBA3.
  2. André F, Ciruelos EM, Juric D, et al. Overall Survival (OS) Results From SOLAR-1, a Phase 3 Study of Alpelisib (ALP) + Fulvestrant (FUL) for Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2-Negative (HER2–) Advanced Breast Cancer (ABC). Presented at ESMO 2020; Abstract LBA18.