The authors of this phase II trial evaluated the PARP inhibitor olaparib in the treatment of 54 patients with metastatic breast cancer (76% ER-positive/HER2-negative) and either germline mutations in non-BRCA1/2 homologous recombination–related DNA repair genes (cohort 1) or somatic mutations in BRCA1/2 or other non-BRCA1/2 homologous recombination–related genes (cohort 2). The objective response rate (ORR) in cohort 1 and cohort 2 were similar (33% and 31%), but confirmed responses were only observed in patients with germline PALB2 (ORR, 82%; PFS, 13.3 months) and somatic BRCA1/2 (ORR 50%; PFS, 6.3 months) mutations.
These findings appear to expand the patient population likely benefit from PARP inhibitors to include those with somatic BRCA1/2 and germline PALB2 mutations, in addition to germline BRCA1/2 mutation carriers.
