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Randomized Controlled Trial
. 2017 Mar 14;116(6):726-730.
doi: 10.1038/bjc.2017.25. Epub 2017 Feb 9.

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

Mary Ellen Moynahan  1 , David Chen  2 , Wei He  2 , Patricia Sung  1 , Aliaksandra Samoila  1 , Daoqi You  1 , Trusha Bhatt  1 , Parul Patel  2 , Francois Ringeisen  3 , Gabriel N Hortobagyi  4 , Jose Baselga  1 , Sarat Chandarlapaty  1
Affiliations
Randomized Controlled Trial

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

Mary Ellen Moynahan et al. Br J Cancer. .

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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Conflict of interest statement

MEM: Grant and personal fees from Novartis; patent related to biomarkers for response to PI3K inhibitors pending. GNH: personal fees from Merck, Eli Lilly, Peregrine Pharmaceuticals, Novartis, and Celgene as consultant; personal fees from Novartis, Bayer, Metastat, Pfizer, Antigen Express, and Galena Biopharma as scientific/advisory committee member. SC: Grant from Novartis and Eli Lilly; personal fees from Foresite Capital, Chugai Pharmaceuticals, Oncotheryeon, and Astra Zeneca. DC, WH, PP, and FR are Novartis employees. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier Plot of Progression-free Survival by PIK3CA mutation status. (A) PIK3CA wild-type vs hotspot mutations. (B) PIK3CA wild-type vs domain-specific hotspot mutations.
See this image and copyright information in PMC

References

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