Pfizer's TALZENNA® with XTANDI® Enhances Survival in Metastatic Castration-Resistant Prostate Cancer

Pfizer Inc. has announced promising findings from the Phase 3 TALAPRO-2 trial, which evaluated the combination of TALZENNA (talazoparib), a PARP inhibitor, with XTANDI (enzalutamide), an androgen receptor pathway inhibitor, in treating patients with metastatic castration-resistant prostate cancer (mCRPC). The study demonstrated that this combination significantly improved overall survival (OS) compared to a placebo combined with XTANDI. This improvement was observed in patients both with and without homologous recombination repair (HRR) gene mutations.

The study included two main cohorts: one unselected cohort and another with patients possessing HRR gene mutations. After a median follow-up of more than four years, cohort 1 saw a median OS of 45.8 months with the TALZENNA and XTANDI combination, compared to 37.0 months for those receiving the placebo plus XTANDI. This marked a 20% reduction in the risk of death and a nearly 9-month increase in median OS versus the standard XTANDI treatment. Detailed results of this cohort were presented by Dr. Neeraj Agarwal at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium.

In cohort 2, comprising patients with HRR-mutated mCRPC, the median OS was 45.1 months for the TALZENNA and XTANDI combination, against 31.1 months for the placebo plus XTANDI. This represented a 38% reduction in the risk of death, translating into a 14-month extension in median OS. This cohort included patients with both BRCA and non-BRCA gene alterations. Dr. Karim Fizazi presented these findings at the ASCO GU symposium.

Dr. Roger Dansey from Pfizer emphasized that the combination of TALZENNA and XTANDI is set to redefine the standard of care for patients with HRR-mutated mCRPC. The results signify the longest median OS reported in a randomized Phase 3 trial for this patient group. Dr. Neeraj Agarwal added that this combination therapy could change clinical practices, offering new hope for those with advanced stages of the disease.

The TALAPRO-2 trial encompassed 1,035 mCRPC patients across multiple regions, including the U.S., Canada, Europe, South America, and the Asia-Pacific. The primary endpoint was radiographic progression-free survival (rPFS), with OS being a key secondary endpoint. Results indicated consistent clinical benefits across both cohorts, aligning with previous analyses published in The Lancet and Nature Medicine.

The safety profile of the TALZENNA and XTANDI combination was largely in line with the known profiles of the individual drugs. Common adverse events included anemia, neutropenia, and fatigue, with severe events like grade 3–4 anemia and neutropenia affecting a significant portion of patients. These side effects were generally manageable through dose modification and supportive care.

Prostate cancer remains a significant health issue worldwide, being the second most common cancer and the fifth leading cause of cancer death among men globally. Metastatic castration-resistant prostate cancer, a particularly aggressive form, develops in 10–20% of prostate cancer cases and poses major treatment challenges.

The combination of TALZENNA and XTANDI has been approved in several countries, including the U.S. and the EU, for treating adults with mCRPC, irrespective of HRR gene mutation status. This dual therapy is a groundbreaking advancement in mCRPC treatment, highlighting the potential for improved patient outcomes and redefining treatment paradigms.