On October 4, Pfizer announced that the oral PARP inhibitor Talzenna (talazoparib) combined with Xtandi (enzalutamide) in the treatment of male patients with metastatic castration-resistant prostate cancer (mCRPC) with or without homologous recombination repair (HRR) gene mutations The Phase III TALAPRO-2 study achieved positive key results.
The study met its primary endpoint in radiographic progression-free survival (rPFS) with a statistically significant and clinically meaningful improvement compared to placebo + Xtandi. The results for the primary endpoint exceeded the prespecified hazard ratio of 0.696. Talzenna is the first PARP inhibitor to demonstrate clinical benefit in patients with mCRPC in combination with Xtandi.
The analysis showed a trend toward improvement in overall survival, the study’s key secondary endpoint, but the data are immature. Benefit was also observed on other secondary endpoints, including investigator-assessed rPFS, prostate-specific antigen (PSA) response rate, time to PSA progression, and overall response rate. Other secondary endpoints are under analysis. The safety profile of Talzenna+Xtandi was largely consistent with the known safety profile of each drug.
Detailed results from TALAPRO-2 will be reported at an upcoming medical congress. Pfizer will also share this data with global regulators to support regulatory scrutiny.
Talzenna or the Talzenna+Xtandi combination has not been approved by any regulatory agency for the treatment of mCRPC. In addition to the TALAPRO-2 trial, the TALAPRO-3 trial, a global, randomized, double-blind, placebo-controlled, phase III study of the Talzenna+Xtandi combination in men with HRR-deficient mCSPC, is ongoing.
Talzenna was approved by the US FDA in 2018 for the treatment of adult patients with germline BRCA-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer.
Metastatic castration-resistant prostate cancer (mCRPC) is cancer that has spread beyond the prostate and progresses despite drug or surgical treatment that lowers testosterone. Approximately 10%-20% of prostate cancer patients develop mCRPC within 5-7 years of diagnosis. In the United States in 2020, approximately 60,000 to 90,000 of the 3 million prostate cancer cases were mCRPC.