Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): results of the Phase 3 SOLAR-1 trial

Date 20 October 2018
Event ESMO 2018 Congress
Session Presidential Symposium 1
Topics Anticancer Agents
Breast Cancer
Presenter Fabrice André
Authors F. André1, E.M. Ciruelos2, G. Rubovszky3, M. Campone4, S. Loibl5, H.S. Rugo6, H. Iwata7, P. Conte8, I.A. Mayer9, B. Kaufman10, T. Yamashita11, Y. Lu12, K. Inoue13, M. Takahashi14, Z. Pápai15, A. Longin16, D. Mills17, C. Wilke17, S. Hirawat18, D. Juric19
  • 1Breast Cancer Unit, Department Of Medical Oncology, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
  • 2Medical Oncology  , Hospital Universitario 12 de Octubre, 28041 - Madrid/ES
  • 3Department Of Medical Oncology And Clinical Pharmacology, National Institute of Oncology Hungary, 1122 - Budapest/HU
  • 4Medical Oncology, ICO Institut de Cancerologie de l'Ouest René Gauducheau, 44805 - Saint-Herblain/FR
  • 5Department Of Medicine And Research, German Breast Group (GBG) Forschungs GmbH, 63263 - Neu-Isenburg/DE
  • 6Breast Cancer Center, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 7Nagoya City University Medical School, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 8Department Of Surgery, Oncology And Gastroenterology, University of Padova, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 9Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, 37232-6838 - Nashville/US
  • 10Oncology, Chaim Sheba Medical Center, Tel Hashomer/IL
  • 11Medical Oncology, Kanagawa Cancer Center, Yokohama/JP
  • 12Hematology/oncology, National Taiwan University Hospital, Taipei/TW
  • 13Medical Oncology, Saitama Cancer Center, Saitama/JP
  • 14Department Of Breast Surgery, Hokkaido Cancer Center, 003-0804 - Sapporo/JP
  • 15Medical Oncology, Duna Medical Center, H-1095 - Budapest/HU
  • 16Oncology, Novartis Pharma S.A.S, F-92506 - Paris/FR
  • 17Oncology, Novartis Pharma AG, CH-4056 - Basel/CH
  • 18Oncology, Novartis Pharmaceuticals Corporation, 07936 - East Hanover/US
  • 19Medical Oncology, Massachusetts General Hospital, 2114 - Boston/US



Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway can occur due to PIK3CA mutations, present in ~40% of patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) ABC. The Phase 3 randomized, double-blind SOLAR‑1 trial (NCT02437318) investigated the efficacy and safety of ALP (α-specific PI3K inhibitor) + FUL in pts with HR+, HER2– ABC.


Men/postmenopausal women with HR+, HER2– ABC and 1 prior line of endocrine therapy were randomized (1:1) to ALP (300 mg/day) + FUL (500 mg every 28 days + Cycle 1 Day 15) or placebo (PBO) + FUL. Primary endpoint was locally assessed progression-free survival (PFS) in the PIK3CA-mutant (mut) cohort; PFS was analyzed in the non-mut cohort as a proof of concept (PoC). Safety was assessed in the total population. Other analyses were tumor response and PFS by important prognostic subgroups, including PIK3CA mutation exon/domain and subtype.


572 pts enrolled; 341 had PIK3CA-mut ABC by tissue. Primary endpoint was met; PFS in the mut cohort was significantly longer with ALP+FUL vs PBO+FUL (HR 0.65; 95% CI 0.50–0.85; P=0.00065; median 11.0 vs 5.7 months [mo]); median follow-up was 20.0 mo. Secondary endpoint of locally assessed PFS in the non-mut cohort did not meet predefined PoC criteria (HR 0.85; 95% CI 0.58–1.25; median 7.4 vs 5.6 mo). In pts with measurable, PIK3CA-mut ABC (n=262), overall response rate was 36% for ALP+FUL vs 16% for PBO+FUL (p=0.0002). Overall, most frequent all-grade (G) adverse events (AEs; single preferred term; ALP+FUL vs PBO+FUL) were hyperglycemia (64% vs 10%), diarrhea (58% vs 16%), nausea (45% vs 22%), decreased appetite (36% vs 10%) and rash (36% vs 6%). G 3/4 hyperglycemia (fasting plasma glucose >250 mg/dL) was observed in 37% of patients for ALP+FUL vs <1% for PBO+FUL; G 3/4 rash in 10% vs <1%. Discontinuations of ALP+FUL/PBO+FUL due to AEs were 5% vs 1%.


ALP+FUL met the primary endpoint by significantly extending PFS vs PBO+FUL and demonstrated a manageable tolerability profile. This is the first study to show statistically significant, clinically meaningful PFS treatment improvement with an α-specific PI3K inhibitor in PIK3CA-mut HR+, HER2– ABC.

Clinical trial identification


May 7, 2015

Editorial Acknowledgement

Editorial assistance was provided by John Munro of ArticulateScience Ltd.