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Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study
Turner, NC Laird, AD Telli, ML Rugo, HS Mailliez, A Ettl, J Grischke, EM Mina, LA Balmaña, J Fasching, PA
Turner, NC
Laird, AD
Telli, ML
Rugo, HS
Mailliez, A
Ettl, J
Grischke, EM
Mina, LA
Balmaña, J
Fasching, PA
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Abstract
These analyses explore the impact of homologous recombination repair gene mutations, including BRCA1/2 mutations and homologous recombination deficiency (HRD), on the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor talazoparib in the open-label, two-cohort, Phase 2 ABRAZO trial in germline BRCA1/2-mutation carriers. In the evaluable intent-to-treat population (N = 60), 58 (97%) patients harbor ≥1 BRCA1/2 mutation(s) in tumor sequencing, with 95% (53/56) concordance between germline and tumor mutations, and 85% (40/47) of evaluable patients have BRCA locus loss of heterozygosity indicating HRD. The most prevalent non-BRCA tumor mutations are TP53 in patients with BRCA1 mutations and PIK3CA in patients with BRCA2 mutations. BRCA1- or BRCA2-mutated tumors show comparable clinical benefit within cohorts. While low patient numbers preclude correlations between HRD and efficacy, germline BRCA1/2 mutation detection from tumor-only sequencing shows high sensitivity and non-BRCA genetic/genomic events do not appear to influence talazoparib sensitivity in the ABRAZO trial.ClinicalTrials.gov identifier: NCT02034916.
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Date
2023
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Collections
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Article
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Turner NC, Laird AD, Telli ML, Rugo HS, Mailliez A, Ettl J, et al. Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study. NPJ breast cancer. 2023 OCT 6;9(1). PubMed PMID: WOS:001093163100001. English.