Pfizer's combination of Talzenna (talazoparib) and Xtandi (enzalutamide) has demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC), according to topline results from the Phase III TALAPRO-2 trial. This benefit was observed not only in patients with homologous recombination repair (HRR) gene mutations but also in the broader population of mCRPC patients, regardless of their biomarker status. The company plans to share the data with global health authorities to potentially expand the approved label for Talzenna.
TALAPRO-2 Trial Details
The TALAPRO-2 trial is an international, double-blind, multicenter, placebo-controlled study involving 1,035 mCRPC patients across the US, Canada, Europe, South America, and the Asia-Pacific region. The trial included two cohorts: an all-comers group and a group with HRR gene mutations. The primary endpoint was radiographic progression-free survival (rPFS), while secondary endpoints included OS, objective response rate (ORR), duration of response (DOR), and prostate-specific antigen (PSA) response.
The combination of Talzenna and Xtandi led to a statistically significant and clinically meaningful improvement in OS compared to Xtandi alone in both the all-comers cohort and the HRR gene-mutated mCRPC patients. The safety profile of the combination was consistent with the known toxicity profiles of the individual medicines.
Clinical Significance
Roger Dansey, Pfizer’s chief development officer for oncology, stated that Talzenna plus Xtandi is the "first and only PARP inhibitor in combination with an ARPI to significantly improve survival" in mCRPC patients, regardless of mutation status. Neeraj Agarwal, global lead investigator for the trial from the Huntsman Cancer Institute, University of Utah, noted that the OS results indicate "potentially practice-changing efficacy" for the combination.
Prostate cancer is the second most common cancer in men worldwide, with an estimated 1.4 million new cases diagnosed in 2022. Up to 20% of patients develop mCRPC within five to seven years of diagnosis. mCRPC is a form of the disease that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone.
Current Treatment Landscape
Talzenna, a PARP inhibitor, blocks the PARP protein, which helps cells repair DNA damage. Xtandi, an androgen receptor pathway inhibitor (ARPI), inhibits the androgen receptor to limit cell proliferation and trigger cell death. The combination was approved by the FDA in June 2023 for mCRPC patients with HRR gene mutations and by the European Commission in January 2024 for those for whom chemotherapy is not clinically indicated.
The new data from TALAPRO-2 will be shared with global health authorities to support potential label expansion, potentially offering a new treatment option for a broader range of mCRPC patients.
