Pfizer appears to have one-upped Johnson & Johnson again in their PARP inhibitor battle in prostate cancer.
After winning a broader FDA label for metastatic castration-resistant prostate cancer (mCRPC), Pfizer’s combination of Talzenna and Xtandi is claiming a phase 3 win that positions it for a wider patient population with metastatic castration-sensitive prostate cancer (mCSPC) compared with J&J’s PARP doublet Akeega.
At the 2026 American Society of Clinical Oncology annual meeting in Chicago, the phase 3 Talapro-3 trial showed that adding the PARP inhibitor Talzenna to Xtandi significantly slashed the risk of radiographic progression or death by 52% in men with homologous recombination repair (HRR) gene-mutated mCSPC.
At three years, 77% of the patients in the Talzenna group and 56% of those in the control group were free from confirmed progression.
Crucially for Pfizer’s market expansion plan, the combination achieved what the New York pharma called consistent radiographic progression-free survival (PFS) benefit across HRR gene alterations, including patients with BRCA and non-BRCA mutations. This broad success comes in contrast with J&J’s Akeega, which earned a narrow FDA green light restricted to patients harboring BRCA2 mutations.
In its own phase 3 trial, dubbed Amplitude, Akeega, a fixed-dose combination of the PARP inhibitor niraparib—sold by GSK as Zejula—and J&J’s Zytiga, also significantly improved rPFS by 37% versus Zytiga alone in a broad HRR gene-mutated mCSPC population. However, the FDA found in an exploratory analysis that patients with BRCA2 mutations drove the bulk of the efficacy with a 54% improvement on rPFS. For the other patients, Akeega only did 12% better than control.
By comparison, in the Talapro-3 trial, Talzenna and Xtandi showed a robust 43% radiographic PFS improvement in the non-BRCA-mutated group, compared with 63% among BRCA-mutated patients. Data favored the Pfizer regimen across several gene subgroups, with the largest effect, 72%, observed in the CDK12 subgroup, followed by 65% with BRCA2 and 57% in ATM, according to results simultaneously published in The New England Journal of Medicine.
“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,” Pfizer’s Chief Oncology Officer Jeff Legos, Ph.D., said in a May 30 statement.
During this interim analysis, overall survival data were immature but favored Talzenna plus Xtandi by 23%. At three years, 78% of patients in the Talzenna combo group and 72% in the control arm were alive.
The regimen’s safety profile showed no surprises, according to Pfizer. The most common grade 3 or higher treatment-emergent adverse event was anemia, which was reported by 51% of patients in the combo group—including 5% who discontinued Talzenna—and 3% in the control group.
Prostate cancer is the second most common cancer in men worldwide, with about 330,000 new cases expected in the U.S. in 2026. About 5% to 10% of newly diagnosed prostate cancer cases are mCSPC, within which 30% harbor HRR gene alterations.
The findings from Talapro-3 underscore the importance of genetic testing in men with metastatic mCSPC, researchers noted in the NEJM article. About a month ago, an FDA advisory committee voted 7 to 1, with 1 abstaining, recognizing a favorable benefit-risk profile of AstraZeneca’s Truqap, in combination with Zytiga and androgen deprivation therapy for patients with PTEN-deficient mCSPC, despite a small 19% improvement in rPFS.
In addition, Novartis’ radioligand therapy Pluvicto plus standard of care also significantly increased rPFS by 28% versus standard of care alone in PSMA-positive mCSPC.