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

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 p...

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Published in:British journal of cancer 2017-03, Vol.116 (6), p.726-730
Main Authors: Moynahan, Mary Ellen, Chen, David, He, Wei, Sung, Patricia, Samoila, Aliaksandra, You, Daoqi, Bhatt, Trusha, Patel, Parul, Ringeisen, Francois, Hortobagyi, Gabriel N, Baselga, Jose, Chandarlapaty, Sarat
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Language:English
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2017.25