The shift is from late to early. Talazoparib, the Pfizer PARP inhibitor sold as Talzenna, started its prostate cancer career paired with enzalutamide in men whose disease had already stopped responding to hormone therapy. In late October 2026, the FDA moved it up the line.
Healio reported that the agency expanded the approval to men with metastatic prostate cancer that has not yet been treated with, or is still sensitive to, androgen pathway drugs, provided their tumours carry homologous recombination repair (HRR) gene mutations. The pairing, with Astellas and Pfizer’s Xtandi (enzalutamide), had been cleared in 2023 only for the resistant stage. Now patients can start it earlier.
What the newer trial showed
The evidence is the phase 3 TALAPRO-3 study, which enrolled 599 patients with HRR-positive disease. Patients were randomised one to one to either talazoparib (0.5 mg once daily) with enzalutamide (160 mg), or a placebo with the same enzalutamide dose. The main measure was radiographic progression-free survival. The combination cut the risk of radiographic progression or death by 52% (HR = 0.48; 95% CI, 0.36-0.65). Overall survival data were immature when that analysis was run.
Neeraj Agarwal, the trial’s lead investigator, stressed that the benefit held for patients with BRCA mutations and for those with other HRR mutations. He called it a response to “a long-standing unmet need” and a reason to test for biomarkers at diagnosis.
The label carries warnings. Prescribing information lists myelodysplastic syndrome and acute myeloid leukemia, myelosuppression and embryo-fetal toxicity. Patients also need a gonadotropin-releasing hormone analog alongside, unless they have had both testicles removed.
Europe went first, and wider
The European route had been quicker, and broader. Urology Times reported in January 2024 that the European Commission had approved the same pair for metastatic castration-resistant prostate cancer in adults who are not candidates for chemotherapy, regardless of mutation status. In the US the FDA label was then limited to HRR gene-mutated disease.
The Commission’s decision rested on the phase 3 TALAPRO-2 trial. Against placebo with enzalutamide, the talazoparib pairing lowered the chance of progression or death by 37% (HR, 0.63; 95% CI, 0.51-0.78). The median radiographic progression-free survival had not been reached in the 402-patient combination arm, against 21.9 months for the 403 patients on placebo. Time to PSA progression ran to 26.7 months with talazoparib and 17.5 months without it. Patients in both arms had a median age of 71.
Robert Jones, a professor of clinical cancer research at the University of Glasgow, said more men at this advanced stage needed options that hold the disease in check for longer. “The European Commission’s approval of talazoparib in combination with enzalutamide offers a meaningful advancement,” he said in a press release.
Watch the dosing, too: the recommended regimen is 0.5 mg of talazoparib by mouth daily with enzalutamide, continued until the disease progresses or toxicity becomes unacceptable.
Sources
- Talazoparib plus enzalutamide approved in EU for mCRPC (Urology Times)
- Talzenna, Xtandi combo grabs FDA approval for earlier metastatic prostate cancer (Healio)
