# SOLAR-1: alpelisib plus fulvestrant for PIK3CA-mutated hormone receptor-positive advanced breast cancer

Source: https://onco.cc/key-papers/paper-solar-1-alpelisib-nejm-2019/  
OnCo record `paper-solar-1-alpelisib-nejm-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Alpelisib, a pill blocking the mutated PI3K-alpha enzyme, nearly doubled the time to progression when added to fulvestrant in advanced breast cancer carrying a PIK3CA mutation, at the cost of high blood sugar and rash.

## Summary

Phase 3 placebo-controlled trial of 572 patients with hormone receptor-positive, HER2-negative advanced breast cancer after an aromatase inhibitor, randomised to alpelisib or placebo with fulvestrant, stratified by PIK3CA mutation status.

In the 341 patients with PIK3CA-mutated tumours, median progression-free survival was 11.0 versus 5.7 months (hazard ratio 0.65); no benefit was seen without the mutation. Hyperglycaemia, rash and diarrhoea led to frequent dose changes.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2019
- DOI: 10.1056/NEJMoa1813904
- Authors: André F, Ciruelos E, Rubovszky G, et al.
- Findings: Median progression-free survival 11.0 vs 5.7 months in PIK3CA-mutated disease; hazard ratio 0.65.; Grade 3 or worse hyperglycaemia in 36.6 percent of alpelisib patients.
- What it means: PIK3CA testing became routine in advanced hormone receptor-positive breast cancer, with alpelisib-fulvestrant the first approved PI3K-targeted regimen; capivasertib and inavolisib now offer alternatives.
- Caveats: Few patients had received a prior CDK4/6 inhibitor.; Toxicity leads to discontinuation in a meaningful minority.

## Sources

- N Engl J Med 2019: https://doi.org/10.1056/NEJMoa1813904
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31091374/

## Connected records

- cancers: [HR-positive metastatic breast cancer after CDK4/6 inhibitors](https://onco.cc/cancers/hr-positive-metastatic-post-cdk46/)
- drugs: [Alpelisib](https://onco.cc/drugs/alpelisib/)
- trials: [SOLAR-1](https://onco.cc/trials/solar-1/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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