137TiP - A phase III study of alpelisib and fulvestrant for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advan...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anticancer Agents
Breast Cancer, Metastatic
Presenter Hiroji Iwata
Citation Annals of Oncology (2016) 27 (suppl_9): ix35-ix41. 10.1093/annonc/mdw577
Authors H. Iwata1, G. Rubovszky2, S. Loibl3, E. Ciruelos4, M. Campone5, D. Juric6, H. Rugo7, I. Mayer8, P.F. Conte9, B. Kaufman10, K. Inoue11, H. Tesch12, Y. Li13, I.D. Mingorance14, L. Ryvo15, H. Iwase16, A. Longin17, D. Mills18, C. Wilke18, F. André19
  • 1Department Of Breast Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 2Internal Medicine-oncology Division "b" And Clinical Pharmacology, Országos Onkológiai Intézet, 7-9 - Budapest/HU
  • 3Medicine And Research, German Breast Group (GBG) Forschungs GmbH, 63263 - Neu-Isenburg/DE
  • 4Breast Cancer Unit, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 5Medical Oncology, ICO Institut de Cancerologie de l'Ouest René Gauducheau, 44805 - St. Herblain/FR
  • 6Hematology/oncology, Massachusetts General Hospital, 02114 - Boston/US
  • 7Department Of Medicine (hematology/oncology), University of California San Francisco Comprehensive Cancer Center, San Francisco/US
  • 81301 Medical Center Dr Suite 1710, Vanderbilt Ingram Cancer Center, 37235 - Nashville/US
  • 9Division Of Surgery,oncology And Gastroenterology, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 10Division Of Oncology, Chaim Sheba Medical Center, 52621 - Ramat Gan/IL
  • 11Division Of Breast Oncology, Saitama Cancer Center, 362 0806 - Saitama/JP
  • 12Onkologie Bethanien, Centrum für Hämatologie und Onkologie Bethanien, 60389 - Frankfurt am Main/DE
  • 13Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 14Optional Medical Oncology Clinical Trials Unit, Hospital Infanta Cristina, 060016 - Badajoz/ES
  • 15Departments Of Oncology, Tel Aviv Sourasky Medical Center-(Ichilov), 64239 - Tel Aviv/IL
  • 16Breast And Endocrine Surgery, Kumamoto University, 860-8556 - Kumamoto/JP
  • 17Oncology Global Development, Novartis pharma S.A.S, 92500 - Paris/FR
  • 18Oncology Global Development, Novartis Pharma AG, 4002 - Basel/CH
  • 19Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR



The PI3K/AKT/mTOR pathway is often dysregulated in HR+ BC and is associated with resistance to endocrine therapy (ET). Alpelisib a PI3Kα-specific inhibitor and fulvestrant showed signs of antitumor activity in patients (pts) with ER+, HER2– ABC (phase I), particularly in PIK3CA-altered tumors.

Trial design

SOLAR-1 (NCT02437318) is a phase III, randomized, double-blind study in men and postmenopausal women with HR+, HER2– ABC. Based on PIK3CA tumor status (mutant vs non-mutant) pts are assigned to 1 of 2 cohorts, and randomized 1:1 to oral alpelisib/placebo (300 mg once daily) and intramuscular fulvestrant (500 mg on Day 1 and 15 of Cycle 1; Day 1 of Cycles ≥2 [28-day cycles]) until disease progression or discontinuation. Randomization is stratified by presence of liver and/or lung metastases and prior CDK4/6 inhibitor therapy. Key inclusion criteria: recurrence or progression on or after AI therapy, ≥1 measurable lesion (RECIST v1.1) or predominantly lytic bone lesion, and ECOG performance status ≤1. Key exclusion criteria: symptomatic visceral disease or disease burden precluding ET, acute pancreatitis ≤1 year prior to screening or history of chronic pancreatitis, and prior therapy with fulvestrant, chemotherapy (except [neo] adjuvant), or PI3K/AKT/mTOR inhibitors. Progression-free survival (PFS; RECIST v1.1; local assessment) and overall survival (OS), in the PIK3CA-mutant cohort are primary and key secondary end-points respectively. PFS (Blinded Independent Central Review; RECIST v1.1), PFS and OS in the PIK3CA non-mutant cohort, the association between PFS and baseline PIK3CA status in circulating tumor DNA, overall response rate, clinical benefit rate, pharmacokinetics and safety are other secondary endpoints. The primary endpoint will be analyzed by a stratified log-rank test at one-sided 2% level of significance. Recruitment of the planned 560 pts is ongoing.

Clinical trial indentification


Legal entity responsible for the study

Novartis Pharmaceutical Corporation


Novartis Pharmaceutical Corporation


S. Loibl: My institution received research funding from Celgene, Amgen, Roche, Pfizer, Teva, Novartis. M. Campone: Novartis: Advisory board grant speaker bureau Menarini: Advisory board Astra Zeneca: Advisory board bureau Pfizer: Advisory board speaker bureau Roche: Advisory board. D. Juric: Advisory role to Novartis, EMD Serono, Eisai, BIND Therapeutics, Natera. Research funding received from Novartis. H. Rugo: Dr. Rugo does not receive funding personally. Funding is provided to her institution for the conduct of clinical trials sponsored by Novartis. I. Mayer: - Research funding and consulting fees from Novartis - Consulting fees from Genentech - Research funding from Clovis. P.F. Conte: Speaker and Advisory Boards for: novartis, roche, eli-lilly, celgene, astra-zeneca, obi Research Grants from: Novartis, Roche, Merck-serono. B. Kaufman: I participated in advisory board for Novartis. AstraZeneca Roche. H. Tesch: Employment or management position Established oncologist in the community oncology practice at the Bethanien Hospital Consulting activities: Novartis, Roche, Pfizer Fees: Novartis, Roche, Pfizer. D. Mills: Own stock in Novartis pharma AG. C. Wilke: Employee of Novartis, the sponsor of the study. F. André: Research support from Novartis. All other authors have declared no conflicts of interest.