Phase 2 study of talazoparib monotherapy in patients with wild-type BRCA1/2 and mutations in other homologous recombination genes

The PARP inhibitor talazoparib is active for advanced breast cancer in patients with germline BRCA1/2 mutations, but its activity beyond gBRCA1/2 is poorly understood. The multicenter phase 2 Talazoparib Beyond BRCA trial in the USA evaluated talazoparib monotherapy for patients with pretreated advanced solid tumors with wild-type gBRCA1/2 and mutations in other homologous recombination (HR) pathway genes. Among 13 breast cancer patients, four had objective response (ORR 31%) and three others had stable disease for at least 6 months (CBR 54%). All patients with germline mutations in PALB2 had treatment-associated tumor regression. The authors conclude that talazoparib has activity in patients with advanced breast cancer who have gPALB2 mutations.