Correlation between PIK3CA mutations in cell-free DNA and everolimus efficacy in HR+, HER2- advanced breast cancer: results from BOLERO-2. Academic Article uri icon

Overview

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.

publication date

  • February 9, 2017

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Biomarkers, Tumor
  • Breast Neoplasms
  • DNA, Neoplasm
  • Mutation
  • Phosphatidylinositol 3-Kinases

Identity

PubMed Central ID

  • PMC5355930

Scopus Document Identifier

  • 85011875111

Digital Object Identifier (DOI)

  • 10.1038/bjc.2017.25

PubMed ID

  • 28183140

Additional Document Info

volume

  • 116

issue

  • 6