Pfizer Inc. (NYSE: PFE) today announced positive topline results from the final prespecified overall survival (OS) analysis of the TALAPRO-2 study of TALZENNA ® (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI ® (enzalutamide), an androgen receptor pathway inhibitor (ARPI), in patients with metastatic castration-resistant prostate cancer (mCRPC). Results showed a statistically significant and clinically meaningful improvement in the final OS in all-comers (cohort 1) as well as in those patients with homologous recombination repair (HRR) gene-mutated mCRPC (cohort 2), compared to XTANDI alone.
"The TALAPRO-2 results showed that TALZENNA plus XTANDI is the first and only PARP inhibitor in combination with an ARPI to significantly improve survival in patients with metastatic castration-resistant prostate cancer, regardless of mutation status," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "Pfizer is dedicated to advancing scientific breakthroughs in genitourinary cancers, and these exciting TALAPRO-2 results further highlight our long-standing commitment to improving survival for men with prostate cancer."
"These overall survival results indicate potentially practice-changing efficacy for TALZENNA in combination with XTANDI for men with metastatic castration-resistant prostate cancer," said Neeraj Agarwal, M.D., FASCO, Professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and global lead investigator for TALAPRO-2. "Metastatic castration-resistant prostate cancer is the most advanced and aggressive stage of the disease, and the TALAPRO-2 results provide much-needed hope to patients who remain in high unmet need for effective treatment options."
At the time of the final analysis, the clinically meaningful improvement in radiographic progression free survival (rPFS) was maintained in both cohorts from the prior primary analysis previously reported and published in The Lancet . In addition, the safety profile of TALZENNA plus XTANDI was generally consistent with the known safety profile of each medicine. Detailed results from TALAPRO-2 will be submitted for presentation at an upcoming medical congress. These data will also be shared with global health authorities to potentially support regulatory filings to update and potentially expand the approved label for TALZENNA.
TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. The combination was also approved by the European Commission in January 2024 for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated. TALZENNA is the first and only PARP inhibitor licensed in the European Union for use with XTANDI for patients with mCRPC, with or without gene mutations. TALZENNA in combination with XTANDI is now approved in more than 35 countries globally for patients with mCRPC.
About Metastatic Castration-Resistant Prostate Cancer
Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death among men worldwide, with an estimated 1.4 million new cases diagnosed in 2022. 1 In the U.S., it is the most common cancer in men. 2 mCRPC is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. Approximately 10%-20% of prostate cancer patients develop mCRPC within 5−7 years of diagnosis. 3 Between 1.2%-2.1% of all prostate cancer cases globally are mCRPC. 4
About TALAPRO-2
The Phase 3 TALAPRO-2 trial is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,035 unique patients with mCRPC (who had not received new life-prolonging systemic treatments after documentation of mCRPC) at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. The study included two patient cohorts: all-comers (n=805, of whom 169 had HRR mutations and 636 did not) and those with HRR gene mutations (n=399, including 169 patients from Cohort 1 and 230 enrolled in Cohort 2). Patients with castrate testosterone levels were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160mg/day.
The primary endpoint of the trial was rPFS, defined as the time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death, whichever occurred first, in both Cohort 1 (all-comers) and Cohort 2 (those with HRRm). Secondary endpoints included OS, objective response rate (ORR), duration of response (DOR), and prostate-specific antigen (PSA) response.
