Pfizer appears to have once again surpassed Johnson & Johnson in the fight against PARP inhibitors in prostate cancer.
Pfizer’s Talzenna and Xtandi combination, which won broader FDA labeling in metastatic castration-resistant prostate cancer (mCRPC), claims a Phase 3 win for a broader patient population with metastatic castration-sensitive prostate cancer (mCSPC) compared to J&J’s PARP doublet drug Akiga.
At the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, the Phase 3 Tarapro 3 trial showed that adding the PARP inhibitor Talzenna to Extandi significantly reduced the risk of radiographic progression or death by 52% in patients with homologous recombination repair (HRR) gene-mutated mCSPC.
After three years, 77% of patients in the Tarzena group and 56% of patients in the control group had no progression.
Crucially for Pfizer’s market expansion plans, the combination achieved what the New York drugmaker calls consistent radiographic progression-free survival (PFS) benefits across HRR gene mutations, including patients with BRCA and non-BRCA mutations. This widespread success is in contrast to J&J’s Akeega, which received narrow FDA approval for patients with BRCA2 mutations.
In a unique Phase 3 trial called Amplitude, Akeega, a fixed-dose combination of the PARP inhibitor niraparib (marketed by GSK as Zejula) and J&J’s Zytiga, also significantly improved rPFS by 37% compared to Zytiga alone in a broadly HRR-mutated mCSPC population. However, the FDA found in an exploratory analysis that patients with BRCA2 mutations improved rPFS by 54% and drove most of the efficacy. For other patients, Akeega performed only 12% better than controls.
By comparison, in the Talapro-3 trial, Talzenna and Xtandi showed a strong radiographic PFS improvement of 43% in the non-BRCA-mutated group compared to 63% in BRCA-mutated patients. The data favored Pfizer’s regimen across several genetic subgroups, with the greatest efficacy of 72% observed in the CDK12 subgroup, followed by 65% for BRCA2 and 57% for ATM, according to results published simultaneously in the New England Journal of Medicine.
Dr. Jeff Legos, Pfizer’s chief oncology officer, said in a May 30 statement: “The benefits seen with Tarzena and Xtandi across the full spectrum of HRR gene alterations strengthen the potential to fundamentally change clinical practice, allowing patients to significantly extend the time it takes for their disease to progress compared to the current standard of care.”
This interim analysis favored Talzenna and Xtandi by 23%, although overall survival data were immature. After three years, 78% of patients in the Talzenna combination group and 72% of patients in the control group were alive.
Pfizer says the regimen’s safety profile was not surprising. The most common grade 3 or higher treatment-emergent adverse event was anemia, reported in 51% of patients in the combination group (including 5% of patients who discontinued Talzenna) and 3% of patients in the control group.
Prostate cancer is the second most common cancer in men worldwide, with approximately 330,000 new cases expected in the United States by 2026. Approximately 5% to 10% of newly diagnosed prostate cancer cases are mCSPC, and 30% of these harbor HRR gene mutations.
Talapro-3 results highlight the importance of genetic testing in patients with metastatic mCSPC, researchers noted in the NEJM paper. About a month ago, an FDA advisory committee voted 7-1, with one abstention, to recognize the favorable benefit-risk profile of AstraZeneca’s Tulkuap plus Zytiga and androgen deprivation therapy for patients with PTEN-deficient mCSPC, despite a modest 19% improvement in rPFS.
Additionally, Novartis’ radioligand therapy Pluvicto plus standard of care also significantly increased rPFS by 28% compared to standard of care alone in PSMA-positive mCSPC.
