Correlation Between PIK3CA Mutations in Cell-free DNA and Everolimus Efficacy in HR, HER2 Advanced Breast Cancer: Results from BOLERO-2

Overview

Journal Br J Cancer

Specialty Oncology

Date 2017 Feb 10

PMID 28183140

Citations 66

Authors

Mary Ellen Moynahan

David Chen

Wei He

Patricia Sung

Aliaksandra Samoila

Daoqi You

Trusha Bhatt

Parul Patel

Francois Ringeisen

Gabriel N Hortobagyi

Jose Baselga

Sarat Chandarlapaty

Affiliations

Soon will be listed here.

Abstract

Background: The current analysis was performed to evaluate the impact of PIK3CA hotspot mutations on everolimus efficacy in BOLERO-2 participants, using cell-free DNA (cfDNA) from plasma samples collected at the time of patient randomisation.

Methods: PIK3CA H1047R, E545K, and E542K mutations in plasma-derived cfDNA were analysed by droplet digital PCR (ddPCR). Median PFS was estimated for patient subgroups defined by PIK3CA mutations in each treatment arm.

Results: Among 550 patients included in cfDNA analysis, median PFS in everolimus vs placebo arms was similar in patients with tumours that had wild-type or mutant PIK3CA (hazard ratio (HR), 0.43 and 0.37, respectively). Everolimus also prolonged median PFS in patients with PIK3CA H1047R (HR, 0.37) and E545K/E542K mutations (HR=0.30) with a similar magnitude.

Conclusions: Mutation analysis of plasma-derived cfDNA by ddPCR suggests that PFS benefit of everolimus was maintained irrespective of PIK3CA genotypes, consistent with the previous analysis of archival tumour DNA by next-generation sequencing.

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