Abstract OT2-01-04: SOLAR-1: A phase III study of alpelisib and fulvestrant in men and postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (BC) progressing on or after aromatase inhibitor (AI) therapy
Authors: Andre F , Kaufman B , Juric D , Ciruelos EM , Iwata H , Mayer IA , Rugo HS , Conte P , Liobl S , Rubovszky G , Inoue K , Tesch H , Lu Y-S , Ryvo L , Longin A-S , Mills D , Wilke C , Germa C , Campone M 
Published: March 2017

Abstract
Background: The phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is often dysregulated in HR+ BC and is associated with resistance to endocrine therapy (ET). Alpelisib (BYL719; PI3Kα-specific inhibitor) and fulvestrant showed signs of antitumor activity in patients (pts) with estrogen receptor-positive (ER+), HER2– advanced BC (phase I), especially in PIK3CA-altered tumors (Janku et al. SABCS 2014, PD5-5).
Methods: SOLAR-1 (NCT02437318) is a phase III, randomized, double-blind study in men and postmenopausal women with HR+, HER2– advanced BC. Pts are assigned to 1 of 2 cohorts based on PIK3CA tumor status (mutant vs non-mutant), 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.
The primary and key secondary endpoints are progression-free survival (PFS; RECIST v1.1; local assessment) and overall survival (OS), respectively, in the PIK3CA-mutant cohort. Other secondary endpoints include PFS and OS in the PIK3CA non-mutant cohort, PFS (Blinded Independent Central Review; RECIST v1.1), the association between PFS and baseline PIK3CA status in circulating tumor DNA, overall response rate, clinical benefit rate, safety, and pharmacokinetics. 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.
Citation Format: Andre F, Kaufman B, Juric D, Ciruelos EM, Iwata H, Mayer IA, Rugo HS, Conte P, Liobl S, Rubovszky G, Inoue K, Tesch H, Lu Y-S, Ryvo L, Longin A-S, Mills D, Wilke C, Germa C, Campone M. SOLAR-1: A phase III study of alpelisib and fulvestrant in men and postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (BC) progressing on or after aromatase inhibitor (AI) therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-04.