Pfizer’s TALZENNA® and XTANDI® Combo Enhances Survival in Metastatic Castration-Resistant Prostate Cancer
Pfizer Inc. (NYSE: PFE) has announced promising results from the Phase 3 TALAPRO-2 study, which tested TALZENNA® (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI® (enzalutamide), an androgen receptor pathway inhibitor (ARPI), for patients with metastatic castration-resistant prostate cancer (mCRPC). The study demonstrated that the combination significantly improved overall survival (OS) compared to placebo plus XTANDI. This was seen in patients both with and without homologous recombination repair (HRR) gene mutations. The results are expected to influence treatment guidelines for mCRPC and will be shared at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco.
The TALAPRO-2 trial included two patient groups: unselected (Cohort 1) and those selected for HRR gene mutations (Cohort 2). The study’s primary endpoint was OS, a prespecified key secondary endpoint. After a median follow-up of 52.5 months, the results showed that patients in Cohort 1 receiving TALZENNA with XTANDI had a median OS of 45.8 months, compared to 37.0 months for those receiving placebo plus XTANDI (Hazard Ratio [HR] of 0.80; 95% Confidence Interval [CI], 0.66-0.96; p=0.015). This reflects a 20% reduction in the risk of death and nearly a 9-month improvement in OS versus the standard of care. This data will be presented by Dr. Neeraj Agarwal, the global lead investigator for the trial, at ASCO GU (Abstract LBA18).
In Cohort 2, which consisted of patients with HRR-mutated mCRPC, the combination treatment also showed significant improvement in OS. With a median follow-up of 44.2 months, the median OS for patients on TALZENNA and XTANDI was 45.1 months, compared to 31.1 months for those on placebo and XTANDI (HR of 0.62; 95% CI, 0.48-0.81; p=0.0005).
This represents a 38% reduction in the risk of death, translating to a 14-month improvement in median OS compared to the standard treatment. This benefit was seen in patients with both BRCA and non-BRCA gene alterations. Dr. Karim Fizazi from Institut Gustave Roussy will present these findings at ASCO GU (Abstract LBA141).
Roger Dansey, M.D., Chief Oncology Officer at Pfizer, commented on the data, noting that TALZENNA in combination with XTANDI has already redefined the standard of care for patients with HRR gene-mutated mCRPC. He emphasized that these new findings show significant OS improvement, potentially shifting the treatment paradigm for mCRPC patients overall. He added that these results may represent the longest median overall survival reported in a Phase 3 trial for mCRPC and expressed Pfizer’s intent to work with global health authorities to update the TALZENNA label with this new data.
Dr. Neeraj Agarwal, global lead investigator for TALAPRO-2, highlighted that the results mark a significant milestone as the first study to demonstrate a meaningful survival benefit from combining PARP inhibitors and androgen receptor inhibitors in mCRPC. He emphasized that survival rates in mCRPC are traditionally poor, and the data from TALAPRO-2 suggest that TALZENNA with XTANDI could be a transformative treatment option.
The trial also assessed secondary endpoints, including radiographic progression-free survival (rPFS), which showed maintained clinical benefit in both cohorts. These findings are consistent with earlier results published in The Lancet and Nature Medicine. The safety profile of TALZENNA combined with XTANDI was consistent with the known safety profiles of both treatments. The most common adverse events in the TALZENNA group (occurring in ≥30% of patients) were anemia, neutropenia, and fatigue, while the most frequent grade 3–4 adverse events were anemia (49%) and neutropenia (19.3%). Most adverse events were manageable with dose adjustments and supportive care.
The results of the TALAPRO-2 study are now being reviewed by regulatory agencies, including the FDA and the European Medicines Agency (EMA), to potentially update the approved labels for TALZENNA.
Metastatic castration-resistant prostate cancer (mCRPC) is an advanced form of prostate cancer that no longer responds to hormonal therapy aimed at lowering testosterone. It remains one of the most challenging cancers to treat, with a poor prognosis. Approximately 10–20% of prostate cancer patients will develop mCRPC within 5 to 7 years after diagnosis, and around 1.2–2.1% of all prostate cancer cases globally are mCRPC.
The TALAPRO-2 trial enrolled 1,035 patients with mCRPC who had not received new life-prolonging treatments. The trial compared TALZENNA (0.5 mg/day) plus XTANDI (160 mg/day) with placebo plus XTANDI (160 mg/day). The primary endpoint was rPFS, and secondary endpoints included OS, objective response rate (ORR), duration of response (DoR), and prostate-specific antigen (PSA) response.
The results of the TALAPRO-2 study offer hope for improving survival in men with mCRPC and could represent a shift in how this aggressive form of prostate cancer is treated.
