Pfizer (NYSE: PFE) announced positive topline results from the Phase III TALAPRO-3 trial evaluating Talzenna (talazoparib) plus Xtandi (enzalutamide) in patients with HRR gene-mutated metastatic castration-sensitive prostate cancer. The TALAPRO-3 study results showed the talazoparib enzalutamide combination met its primary endpoint of radiographic progression-free survival, with the hazard ratio exceeding the pre-specified efficacy threshold, and an interim analysis demonstrated a trend toward improved overall survival.
Trial Design and Patient Population
The TALAPRO-3 trial (NCT04821622) is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 599 patients with metastatic castration-sensitive prostate cancer harboring alterations in one or more of 12 HRR genes. Patients had received no more than three months of androgen deprivation therapy, with or without an approved androgen receptor pathway inhibitor in the mCSPC setting, and were randomized to receive either talazoparib 0.5 mg daily plus enzalutamide 160 mg daily or placebo plus enzalutamide 160 mg daily. Sites spanned the United States, Canada, Europe, South America, and the Asia-Pacific region.
Efficacy Results From the TALAPRO-3 Study
The primary endpoint, investigator-assessed radiographic progression-free survival defined by RECIST 1.1 for soft tissue and PCWG3 criteria for bone, was met with a statistically significant reduction in the risk of disease progression or death for the talazoparib enzalutamide combination versus placebo plus enzalutamide. The company reported that the observed hazard ratio exceeded the pre-specified target of 0.63, and that the majority of patients in the trial remained progression-free at the time of analysis. Consistent rPFS benefit was observed across patients whose tumors harbored BRCA alterations and those with non-BRCA HRR gene mutations, according to the data.
At the interim analysis, overall survival — a key secondary endpoint — showed what Pfizer described as a strong trend toward improvement, though the data were not yet mature. Benefits were also reported across other secondary endpoints, including objective response rate, duration of response, and time to PSA progression.
Pfizer did not disclose the specific hazard ratio, median rPFS values, or the number of events in either arm. The absence of these quantitative details limits independent assessment of the magnitude of benefit, and the full dataset is expected at an upcoming medical congress.
Safety Profile of Talzenna Plus Xtandi in Metastatic Prostate Cancer Treatment
The safety profile of the combination was consistent with the known adverse event profiles of each agent. No new safety signals were identified. Based on prior data from the TALAPRO-2 trial in mCRPC, the combination carries established risks of myelosuppression — Grade 3 or higher anemia, neutropenia, and thrombocytopenia were reported in 48%, 19%, and 9% of patients, respectively, in that earlier study. Red blood cell transfusions were required in 42% of patients in TALAPRO-2. Myelodysplastic syndrome and acute myeloid leukemia have been reported at low rates (less than 0.5%) across the talazoparib clinical program. Whether the myelosuppression rates in TALAPRO-3 differ from those observed in the mCRPC setting was not disclosed.