Which statement identifies markers used to determine eligibility for PARP inhibitors?

Which statement identifies markers used to determine eligibility for PARP inhibitors?

• A. Germline BRCA mutation
• B. Somatic BRCA mutation
• C. PD-L1 expression
• D. MSI status

Answer: (A)

PARP inhibitors exploit a vulnerability in tumor cells with BRCA-related homologous recombination deficiency. The strongest and most widely used marker to identify eligibility is a germline BRCA mutation, because inherited BRCA1/2 mutations indicate defective DNA repair that makes tumors particularly sensitive to PARP inhibition. PD-L1 expression and MSI status are signals used for different therapies (immune checkpoint inhibitors and mismatch repair–deficient tumors, respectively) and do not identify BRCA-related sensitivity to PARP inhibitors. Somatic BRCA mutations can also inform use in some settings, but germline BRCA mutation remains the classic, most consistently applied marker for determining eligibility.

PARP inhibitors exploit a vulnerability in tumor cells with BRCA-related homologous recombination deficiency. The strongest and most widely used marker to identify eligibility is a germline BRCA mutation, because inherited BRCA1/2 mutations indicate defective DNA repair that makes tumors particularly sensitive to PARP inhibition. PD-L1 expression and MSI status are signals used for different therapies (immune checkpoint inhibitors and mismatch repair–deficient tumors, respectively) and do not identify BRCA-related sensitivity to PARP inhibitors. Somatic BRCA mutations can also inform use in some settings, but germline BRCA mutation remains the classic, most consistently applied marker for determining eligibility.