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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 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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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. |
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ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/bjc.2017.25 |