Pfizer has unveiled late-stage clinical data showing its drug combination could significantly delay disease progression in a difficult-to-treat form of prostate cancer.

 

This marks one of the most closely watched oncology readouts at this year’s medical congress.

 

Results from the Phase 3 TALAPRO-3 study show that the combination of TALZENNA (talazoparib) and XTANDI (enzalutamide) cut the risk of radiographic disease progression or death by 52% compared with XTANDI alone.

 

The hazard ratio of 0.48 translated into a striking separation in long-term outcomes. At three years, 77% of patients on the combination remained progression-free versus 56% in the control arm. Median radiographic progression-free survival has not yet been reached in the combination group, compared with 46 months for placebo plus XTANDI.

 

“Delaying progression to castration-resistant disease, the most symptomatic and lethal phase of prostate cancer, remains a significant challenge to patients with mCSPC – especially to those with HRR gene alterations, who often experience poorer outcomes,” said Neeraj Agarwal, global lead investigator for TALAPRO-3. 

 

“With more than three years of follow-up and median radiographic progression-free survival not reached, TALZENNA plus XTANDI demonstrated durable disease control across a broad HRR-altered population, including patients with BRCA and non-BRCA alterations. These findings underscore the importance of genetic testing as part of routine care and highlight the potential for TALZENNA plus XTANDI to meaningfully improve the outcomes of patients with HRRm mCSPC.”

 

Benefit was consistent across patient subgroups, including those defined by age, PSA levels, tumor grade, geography, and gene alteration status. In patients with BRCA-altered disease, the risk reduction reached 63% while non-BRCA patients saw a 43% reduction.

 

Interim overall survival data also showed a favorable trend, though not statistically definitive. Median overall survival was not reached in either arm. The combination also significantly delayed PSA progression and the need for subsequent therapy, both with hazard ratios of 0.51.

 

“The benefit seen with TALZENNA plus XTANDI across a full spectrum of HRR gene alterations reinforces its potential to fundamentally change clinical practice, giving patients significantly more time before disease progression as compared to the current standard of care," said Jeff Legos, Chief Oncology Officer at Pfizer.

 

Safety findings were consistent with known profiles of both drugs. The most common side effects included anemia, fatigue, and decreased neutrophil counts. Grade 3 or higher anemia occurred in 51% of patients receiving the combination versus 3% in the control arm, making it the most significant toxicity observed. Five percent of patients discontinued treatment due to anemia.

 

Despite the toxicity profile, investigators reported that adverse events were generally manageable with dose adjustments and supportive care.

 

The study focused on men with homologous recombination repair (HRR) gene–mutated metastatic castration-sensitive prostate cancer, an aggressive subtype of Prostate cancer that accounts for up to 30% of cases in advanced disease settings.

 

Pfizer said the results are being discussed with global regulators as part of potential efforts to expand the therapy’s approved uses. The combination is already authorized in more than 60 countries for other forms of advanced prostate cancer.

 

The TALAPRO-3 trial enrolled 599 patients across multiple continents and is continuing, with final overall survival analysis still pending.