Talazoparib demonstrated antitumor activity in men with heavily pretreated, metastatic, castration-resistant prostate cancer (mCRPC) who had alterations in homologous recombination repair (HRR) genes, according to phase 2 results published in The Lancet Oncology

The phase 2 TALAPRO-1 trial (ClinicalTrials.gov Identifier: NCT03148795) enrolled 128 patients with mCRPC and gene alterations likely to confer sensitivity to PARP inhibition (ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, and RAD51C).

The patients had previously received 1 or 2 taxane-based chemotherapy regimens for metastatic disease, and they had progressed on enzalutamide, abiraterone, or both.

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There were 127 patients who received at least 1 dose of oral talazoparib (safety population) and 104 patients who had measurable soft-tissue disease (antitumor activity population).

Patients received talazoparib (0.75 mg or 1 mg per day) until disease progression, unacceptable toxicity, investigator decision, withdrawal of consent, or death. The median duration of  treatment was 6.1 months in the safety population and 6.2 months in the antitumor activity population.

At a median follow-up of 16.4 months, the objective response rate (ORR) was 29.8%. The ORR was 50% in patients with BRCA1 alterations, 46% in those with BRCA2 alterations, 25% in those with PALB2 alterations, and 12% in patients with ATM alterations.

Most patients had a reduction in tumor burden (80%), prostate-specific antigen (PSA) level (72%), and circulating tumor cell (CTC) count (82%).

Among patients with BRCA1/2 alterations, 90% had a reduction in tumor burden, 85% had a reduction in PSA level, and 93% had a reduction in CTCs. Most patients with PALB2 or ATM alterations also had reductions in tumor burden, PSA level, and CTCs.

The most common grade 3-4 treatment-emergent adverse events (AEs) were anemia (31%), thrombocytopenia (9%), and neutropenia (8%). Serious treatment-emergent AEs occurred in 34% of patients. There were no treatment-related deaths.

“These data suggest that talazoparib has durable antitumor activity against lethal prostate cancers with various DNA repair defects that directly or indirectly impact HRR,” the study authors wrote. “The favorable benefit-risk profile supports the study of talazoparib in larger, randomized clinical trials, including in men with non-BRCA alterations.”

Disclosures: This research was supported by Pfizer/Medivation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


de Bono JS, Mehra N, Scagliotti GV, et al. Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): An open-label, phase 2 trial. Lancet Oncol. Published August 10, 2021. doi:10.1016/S1470-2045(21)00376-4