Abstract CT142: Prevalence of PIK3CAmutations in patients with hormone receptor-positive, human epidermal growth factor-2-negative advanced breast cancer from the SOLAR-1 trial
Authors: Rugo Hope S. , Mayer Ingrid , Conte Pierfranco , Loibl Sibylle , Campone Mario , Juric Dejan , Andre Fabrice , Fritzemeier Marilyn , He Wei , Babbar Naveen , Ciruelos Eva 
Published: August 2019

Abstract
Introduction: Approximately 40% of patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) exhibit mutations in the PIK3CA gene, leading to phosphatidylinositol-3-kinase (PI3K) pathway hyperactivation. Use of the oral α-specific PI3K inhibitor alpelisib (ALP) + fulvestrant (FUL) in SOLAR-1 significantly improved progression-free survival (HR 0.65; P&lt;0.01) and objective response rate (measurable disease: ALP arm, 36%; placebo arm, 16%; P&lt;0.001) in the PIK3CA mutant (mut) cohort; in the non-mut cohort, clinically relevant benefit was not observed. Here we present the prevalence of PIK3CA mutations in SOLAR-1.
Methods: SOLAR-1 (N=572) is a randomized, double-blind, phase 3 study of ALP 300 mg once daily + FUL 500 mg every 28 days + Cycle 1 Day 15, in men and postmenopausal women with HR+, HER2- ABC whose disease progressed on/after an aromatase inhibitor. Tumor tissue was analyzed by PCR-based Novartis clinical trial assay or QIAGEN therascreen® PIK3CA RGQ PCR to determine PIK3CA status and assign pts to cohorts. Pts in the mut cohort had mutations in hotspots in exons 7, 9, and 20 (Table), reflecting mutations common in pts with HR+ BC and sensitive to ALP in vitro.
Results: Using archival tumor tissue (92%) and fresh biopsies (8%) from randomized pts, 341 had a detectable PIK3CA mutation per primary (n=262) or metastatic (n=74) tumor or unknown (n=5); 231 had no detectable PIK3CA mutation per primary (n=174) or metastatic (n=51) tumor or unknown (n=6). Mutations in exon 20, H1047, were most prevalent (n=193; 57%); E545 (n=106; 31%), E542K (n=60; 18%), C420R (n=6; 2%), and Q546 (n=5; 1%) were also observed.
Conclusions: Analysis of these data is the first step in investigating PIK3CA alterations in SOLAR-1. Further results beyond PIK3CA mutation hotspots from next-generation sequencing will be shared at the congress. NCT02437318.
Table.PIK3CA MutationsExon 7C420RExon 9E542K; E545A; E545D; E545G; E545K; E545Xa; Q546E; Q546R; Q546XaExon 20H1047L; H1047R; H1047Xa; H1047YaThe Novartis clinical trial assay does not differentiate all mutations and reports E545X for E545A/D/G/K mutations, Q546X for Q546E/K/R mutations, and H1047X for H1047L/R/Y mutations.
Citation Format: Hope S. Rugo, Ingrid Mayer, Pierfranco Conte, Sibylle Loibl, Mario Campone, Dejan Juric, Fabrice Andre, Marilyn Fritzemeier, Wei He, Naveen Babbar, Eva Ciruelos. Prevalence of PIK3CAmutations in patients with hormone receptor-positive, human epidermal growth factor-2-negative advanced breast cancer from the SOLAR-1 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT142.