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SOLAR-1

Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer

Phase 3N = 572NCT02437318

Population
Men and postmenopausal women with HR-positive, HER2-negative advanced breast cancer previously treated with endocrine therapy; 341 had confirmed PIK3CA-mutated tumours
Design
Randomized, double-blind phase 3 trial of alpelisib 300 mg per day plus fulvestrant versus placebo plus fulvestrant; two cohorts by tumour-tissue PIK3CA mutation status
Primary endpoint
PFS
Arms
  • Alpelisib plus fulvestrant (experimental): Alpelisib 300 mg per day plus fulvestrant 500 mg every 28 days and once on day 15
  • Placebo plus fulvestrant (control): Placebo plus fulvestrant 500 mg every 28 days and once on day 15
People
André F, SOLAR-1 Study Group
PFSHR 0.65 (95% CI 0.50–0.85)Δ median PFS+5.3 monthsPFSHR 0.85 (95% CI 0.58–1.25)OSHR 0.86 (95% CI 0.64–1.15)Δ median OS+7.9 months
Show the numbers
Results reported for SOLAR-1
EndpointAnalysisAlpelisib plus fulvestrantPlacebo plus fulvestrantEffect
PFSPIK3CA-mutated cohort (n=341)primarymedian follow-up 20 monthsAndré 2019median 11 months (7.5–14.5)median 5.7 months (3.7–7.4)HR 0.65 (95% CI 0.50–0.85)P<0.001Investigator-assessed; primary endpoint in the PIK3CA-mutated cohort.
PFSCohort without PIK3CA-mutated cancerexploratoryAndré 2019——HR 0.85 (95% CI 0.58–1.25)Posterior probability of hazard ratio below 1.00 was 79.4% (Bayesian analysis as reported).
OSPIK3CA-mutated cohort (n=341)finalAndré 2021median 39.3 months (34.1–44.9)median 31.4 months (26.8–41.3)HR 0.86 (95% CI 0.64–1.15)P=0.15Did not cross the prespecified efficacy boundary (P of 0.0161 or lower); a 7.9-month numerical difference in median OS.
Results reported for SOLAR-1
EndpointAnalysisAlpelisib plus fulvestrantPlacebo plus fulvestrantEffect
PFSPIK3CA-mutated cohort (n=341)primarymedian follow-up 20 monthsAndré 2019median 11 months (7.5–14.5)median 5.7 months (3.7–7.4)HR 0.65 (95% CI 0.50–0.85)P<0.001Investigator-assessed; primary endpoint in the PIK3CA-mutated cohort.
PFSCohort without PIK3CA-mutated cancerexploratoryAndré 2019——HR 0.85 (95% CI 0.58–1.25)Posterior probability of hazard ratio below 1.00 was 79.4% (Bayesian analysis as reported).
OSPIK3CA-mutated cohort (n=341)finalAndré 2021median 39.3 months (34.1–44.9)median 31.4 months (26.8–41.3)HR 0.86 (95% CI 0.64–1.15)P=0.15Did not cross the prespecified efficacy boundary (P of 0.0161 or lower); a 7.9-month numerical difference in median OS.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.650.5–0.85
PFS0.850.58–1.25
OS0.860.64–1.15
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Alpelisib plus fulvestrant (experimental)
  • Placebo plus fulvestrant (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsAlpelisib plus fulvestrantPlacebo plus fulvestrant
0100.0%100.0%
764.3%42.7%
1441.4%18.2%
2126.6%7.8%
2817.1%3.3%
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%020406080Months (modelled)
  • Alpelisib plus fulvestrant (experimental)
  • Placebo plus fulvestrant (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsAlpelisib plus fulvestrantPlacebo plus fulvestrant
0100.0%100.0%
2564.3%57.6%
4942.1%33.9%
7427.1%19.5%
9817.8%11.5%
Primary publication: André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380(20):1929-1940. PubMedDOI

Appears in

Sources

  1. André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380(20):1929-1940.

    PubMedDOI

  2. André F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA, et al. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021;32(2):208-217.

    PubMedDOI