Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study

BACKGROUND: Talazoparib, a poly(ADP-ribose) polymerase enzyme inhibitor, is approved for the treatment of patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative advanced breast cancer. This two-part study, a recently published dose-escalation part followed by the dose-expansion part reported here, evaluated the efficacy and safety of talazoparib in Japanese patients with gBRCA1/2-mutated advanced breast cancer. METHODS: In this open-label, multicenter phase 1 study (NCT03343054), the primary endpoint of the dose-expansion part was confirmed objective response rate (ORR), determined by investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Patients received the recommended phase 2 dose (1 mg/day; 0.75 mg/day moderate renal impairment). RESULTS: Nineteen Japanese patients with gBRCA1/2-mutated locally advanced or metastatic breast cancer were enrolled. Confirmed ORR was 57.9% (11/19; 90% confidence interval [CI] 36.8–77.0). Stable disease was observed in 36.8% (7/19) of patients. Per investigator assessment, median PFS was 7.2 months (95% CI 4.1–not estimable) and 12-month OS rate was 84.7% (90% CI 57.5–95.1). Median OS was not reached; 17/19 patients were alive and censored at 12 months. All patients experienced treatment-related adverse events (AEs); the majority were hematologic. The most common treatment-related AE was anemia (68.4%; [13/19]). Grade 3/4 treatment-related AEs were observed in 52.6% (10/19) of patients. During the safety period, there were no grade 5 treatment-emergent AEs, treatment-related serious AEs, or deaths. CONCLUSIONS: In Japanese patients with gBRCA mutations and locally advanced or metastatic breast cancer, talazoparib monotherapy was generally well tolerated and resulted in clinically meaningful ORRs. CLINICALTRIALS.GOV IDENTIFIER: NCT03343054. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12282-022-01390-w.