LBA18 - Overall survival (os) results from SOLAR-1, a phase III study of alpelisib (ALP) + fulvestrant (FUL) for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC)

Background

Phosphatidylinositol 3-kinase (PI3K) pathway hyperactivation due to PIK3CA mutations contributes to poor survival in patients (pts) with HR+, HER2– ABC (Mosele 2020). In the phase III SOLAR-1 trial of pts with progression on/after aromatase inhibitor (AI), the PI3Kα inhibitor ALP together with FUL significantly improved progression-free survival (PFS) in the PIK3CA-mutant (mut) cohort (HR 0.65; 95% CI 0.50-0.85; P<0.001; median [m] PFS 11.0 mo with ALP + FUL vs 5.7 mo with placebo [PBO] + FUL), a population with poor prognosis. At final PFS analysis, the first interim OS results were immature.

Methods

Men/postmenopausal women (N=572) with HR+, HER2– ABC with no prior chemotherapy treatment (tx) and whose disease progressed on/after AI were randomized 1:1 to receive ALP (300 mg PO QD) or PBO, + FUL (500 mg IM on D1 and D15 of C1 then D1 of each 28-d cycle) and stratified by presence of lung and/or liver metastases and prior cyclin-dependent kinase 4/6 inhibitor. OS in the PIK3CA-mut cohort, a key secondary endpoint, was evaluated by Kaplan-Meier methodology; a 1-sided stratified log-rank test was performed with an O’Brien-Fleming efficacy boundary of P≤0.0161.

Results

With mOS follow-up of 30.8 mo, mOS was 39.3 mo (95% CI 34.1-44.9) with ALP + FUL and 31.4 mo (95% CI 26.8-41.3) with PBO + FUL (HR 0.86; 95% CI 0.64-1.15; P=0.15); OS did not cross the prespecified boundary. Median time to chemotherapy (TTC) was 23.3 mo (95% CI 15.2-28.4) with ALP + FUL and 14.8 mo (95% CI 10.5-22.6) with PBO + FUL (HR 0.72; 95% CI 0.54-0.95). In pts with lung and/or liver metastases, mOS was 37.2 mo (95% CI 28.7-43.6) with ALP + FUL and 22.8 mo (95% 19.0-26.8) with PBO + FUL (HR 0.68; 95% CI 0.46-1.00). No new safety signals were observed with longer follow-up.

Conclusions

Though not statistically significant, OS was prolonged by a clinically relevant ≈8 mo with ALP when added to FUL in HR+, HER2−, PIK3CA-mut ABC. mTTC was also prolonged with ALP + FUL vs PBO + FUL. Coupled with the statistically and clinically significant PFS, these data further support ALP + FUL in this poorer prognostic population of pts with PIK3CA-mut ABC.

Clinical trial identification

NCT02437318.

Editorial acknowledgement

We thank Rob M. Camp, PhD, of Healthcare Consultancy Group, LLC, for his medical editorial assistance with this abstract, which was funded by Novartis Pharmaceuticals.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

F. André: Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Daiichi Sankyo. E.M. Ciruelos: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self): AstraZeneca. D. Juric: Research grant/Funding (self): Novartis; Advisory/Consultancy: Genentech; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: EMD Serono. S. Loibl: Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Celgene; Honoraria (institution), Research grant/Funding (institution): Amgen; Honoraria (institution), Research grant/Funding (institution): Roche; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): AbbVie; Honoraria (institution): Eli Lilly; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (institution): Eirgenix; Honoraria (institution): Seattle Genetics; Honoraria (institution): PriME/ Medscape; Honoraria (self): Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution): Samsung; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Puma; Honoraria (institution): MSD; Research grant/Funding (institution): Immunomedics. M. Campone: Research grant/Funding (institution), Non-remunerated activity/ies: Novartis; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Advisory/Consultancy: Servier; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Accord; Research grant/Funding (institution): Tesaro; Advisory/Consultancy: Eli Lilly. I. Mayer: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Seattle Genetics; Research grant/Funding (institution): Pfizer; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Puma. G. Rubovszky: Honoraria (self): Novartis. T. Yamashita: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): Eisai; Honoraria (self): Novartis; Honoraria (self): Taiho; Honoraria (self), Research grant/Funding (institution): Nippon Kayaku; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Kyowa Kirin; Honoraria (self): Pfizer Japan; Honoraria (self): Eli Lilly; Honoraria (self): Daiichi Sankyo. B. Kaufman: Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): AbbVie. Y-S. Lu: Advisory/Consultancy, Speaker Bureau/Expert testimony, Clinical study trial fee: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): GlaxoSmithKline. K. Inoue: Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Parexel/Puma Biotechnology; Research grant/Funding (institution): MSD; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Sanofi. M. Takahashi: Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Nippon Kayaku; Research grant/Funding (institution): Taiho. F. Ghaznawi: Full/Part-time employment: Novartis Pharmaceuticals Corporation. D. Mills: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharma AG. M. Kaper, M. Miller: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceuticals Corporation. P.F. Conte: Speaker Bureau/Expert testimony: Genenetech/Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck Serono; Travel/Accommodation/Expenses: Celgene. H. Iwata: Honoraria (self), Advisory/Consultancy: Daiichi-Sankyo; Honoraria (self), Advisory/Consultancy: Chugai/Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Uncompensated member of the steering committee for the SOLAR-1 trial: Novartis; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self): Eisai; Honoraria (self): Taiho; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Odonate; Advisory/Consultancy: Kyowa Hako Kirin; Honoraria (self), Advisory/Consultancy: AstraZeneca. H.S. Rugo: Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution): Odonate Therapeutics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi-Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: Macrogenics; Travel/Accommodation/Expenses: Mylan; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Immunomedics; Advisory/Consultancy: Samsung; Advisory/Consultancy: Puma; Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Sermonix; Research grant/Funding (institution): Seattle Genetics. All other authors have declared no conflicts of interest.