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Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast CancerTalazoparib in Germline BRCA1/2-Mutated Breast Cancer
Abstract
Purpose
PARP inhibitors (PARPi) have demonstrated efficacy in tumors with germline breast cancer susceptibility genes (gBRCA) 1 and 2 mutations, but further factors influencing response to PARPi are poorly understood.Experimental design
Breast cancer tumor tissue from patients with gBRCA1/2 mutations from the phase III EMBRACA trial of the PARPi talazoparib versus chemotherapy was sequenced using FoundationOne CDx.Results
In the evaluable intent-to-treat population, 96.1% (296/308) had ≥1 tumor BRCA (tBRCA) mutation and there was strong concordance (95.3%) between tBRCA and gBRCA mutational status. Genetic/genomic characteristics including BRCA loss of heterozygosity (LOH; identified in 82.6% of evaluable patients), DNA damage response (DDR) gene mutational burden, and tumor homologous recombination deficiency [assessed by genomic LOH (gLOH)] demonstrated no association with talazoparib efficacy.Conclusions
Overall, BRCA LOH status, DDR gene mutational burden, and gLOH were not associated with talazoparib efficacy; however, these conclusions are qualified by population heterogeneity and low patient numbers in some subgroups. Further investigation in larger patient populations is warranted.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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