Litton JK, et al. - Given the antitumor activity of the poly(adenosine diphosphate–ribose) inhibitor talazoparib in patients with advanced breast cancer and germline mutations in BRCA1 and BRCA2 (BRCA1/2), researchers compared the effect of talazoparib (1 mg once daily) vs standard single-agent therapy of the physician’s choice (capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21-day cycles) on the progression-free survival of patients with advanced breast cancer and a germline BRCA1/2 mutation. Outcomes revealed a significantly beneficial effect of single-agent talazoparib over standard chemotherapy with respect to progression-free survival. Talazoparib led to superior patient-reported outcomes.

Methods

• In a randomized, open-label, phase 3 trial, researchers assigned patients with advanced breast cancer and a germline BRCA1/2 mutation, in a 2:1 ratio, to receive talazoparib (1 mg once daily) or standard single-agent therapy of the physician’s choice (capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21-day cycles).
• Progression-free survival, which was assessed by blinded independent central review, was assessed as the primary end point.

Results

• Researchers randomized 431 patients; of these, 287 received talazoparib and 144 received standard therapy.
• The talazoparib group showed significantly longer median progression-free survival than the standard-therapy group (8.6 months vs 5.6 months; hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P < 0.001).
• For death, the interim median hazard ratio was 0.76 (95% CI, 0.55 to 1.06; P=0.11 [57% of projected events]).
• The talazoparib group had higher objective response rate than the standard-therapy group (62.6% vs 27.2%; odds ratio, 5.0; 95% CI, 2.9 to 8.8; P < 0.001).
• In this trial, 55% of the patients who received talazoparib showed hematologic grade 3–4 adverse events (primarily anemia) vs 38% of the patients who received standard therapy; nonhematologic grade 3 adverse events occurred in 32% and 38% of the patients, respectively.
• Talazoparib also resulted in more favorable patient-reported outcomes; researchers observed significant overall improvements and significant delays in the time to clinically meaningful deterioration according to both the global health status–quality-of-life and breast symptoms scales.