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

Br J Cancer. 2017 Mar 14;116(6):726-730. doi: 10.1038/bjc.2017.25. Epub 2017 Feb 9.

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 types

  • Randomized Controlled Trial

MeSH terms

  • Androstadienes / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell-Free System
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Mutational Analysis
  • DNA, Neoplasm / blood*
  • DNA, Neoplasm / genetics*
  • Everolimus / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Mutation / genetics*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / genetics*
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate

Substances

  • Androstadienes
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Everolimus
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • exemestane