SOLAR-1
In PIK3CA-mutated HR-positive/HER2-negative advanced breast cancer progressing after endocrine therapy, does alpelisib plus fulvestrant improve PFS?
Trial design and population
572 patients with HR-positive/HER2-negative advanced breast cancer; primary efficacy cohort had a PIK3CA mutation in tumour tissue.
Alpelisib 300 mg orally daily plus fulvestrant 500 mg IM vs placebo plus fulvestrant.
572
PFS in PIK3CA-mutated cohort
Key results
In the PIK3CA-mutated cohort, median PFS was 11.0 vs 5.7 months (HR 0.65, 95% CI 0.50–0.85; P<.001). Final median OS was 39.3 vs 31.4 months (HR 0.86, 95% CI 0.64–1.15; not statistically significant).
Source-reported outcome visualization
Median progression-free survival · Primary analysis
Source-reported endpoint and unit. Median survival is not converted into an NNT.
Absolute Effect
Median PFS difference 5.3 months is not an NNT. OS improvement was not statistically significant.
NNT: Not calculated; median PFS difference is not a valid NNT. Do not convert median survival differences into NNT.
NNH: Not quantifiable. Grade 3+ hyperglycaemia about 37%, rash about 10%, diarrhoea about 7%; approximately one-quarter discontinued alpelisib due to AEs. Screen/manage diabetes risk, glucose and rash early.
Safety and treatment burden
Grade 3+ hyperglycaemia about 37%, rash about 10%, diarrhoea about 7%; approximately one-quarter discontinued alpelisib due to AEs. Screen/manage diabetes risk, glucose and rash early.
Follow-up, maturity and limitations
Primary PFS and later final OS analyses.
Requires PIK3CA mutation confirmation. Trial predates widespread first-line CDK4/6 inhibitor use; evidence after CDK4/6 inhibitors is less directly represented.
Clinical interpretation
Current-practice context · reviewed 20 October 2026
Historical evidence is separated from current sequencing. Confirm current guidelines, local regulatory status, biomarkers, prior therapies and patient-specific contraindications. Newer treatments may have changed the preferred sequence; where NNT/NNH cannot be defensibly quantified, no surrogate calculation is made.