PARP inhibitors (PARPi) have been found to be effective in treating germline breast cancer susceptibility genes (gBRCA 1 and 2 mutations), however there were still a number of unknowns regarding how these factors influence response. FoundationOne CDx was used to sequence tumor tissue from patients with gBRCA1/2 mutations who received PARPi talazoparib in the phase III EMBRACA trial. There was excellent concordance (95.3%) between tBRCA and gBRCA mutation status in the evaluable intent-to-treat population, with 96.1% (296/308) having at least 1 tumor BRCA (tBRCA) change. The efficacy of talazoparib was not associated with genetic/genomic features including BRCA loss of heterozygosity (LOH; detected in 82.6% of evaluable patients), DNA damage response (DDR) gene mutation burden, and tumor homologous recombination deficiency [assessed by genomic LOH (gLOverall, talazoparib efficacy was not linked to BRCA LOH status, DDR gene mutation burden, or gLOH. However, in certain subgroups, the conclusions are tempered by population heterogeneity and low patient counts. Additional study in larger patient groups is needed.

Source:aacrjournals.org/clincancerres/article/28/7/1383/682213/Determinants-of-Response-to-Talazoparib-in