Pfizer bags a hormone-sensitive win
Talapro-3 could help move Talzenna into earlier prostate cancer.
Talapro-3 could help move Talzenna into earlier prostate cancer.
It looks like a case of better late than never for Pfizer’s Talapro-3 trial of the PARP inhibitor Talzenna in hormone-sensitive prostate cancer. The study, testing an Xtandi combo in homologous recombination repair mutations, was a hit, the company said on Thursday. Results had once been expected in 2024.
Success could expand the market for Talzenna, which is currently approved alongside Xtandi in HRR-mutated castrate-resistant prostate cancer. Still, Johnson & Johnson’s Akeega has got there first with an FDA hormone-sensitive approval last December.
Pfizer could be hoping to go broader. Akeega, a fixed-dose combo of the active ingredients of Zejula and Zytiga, got the nod for patients with BRCA2 mutations – one type of HRR alteration. Pfizer said Talapro-3 showed a consistent benefit across patients with BRCA and non-BRCA mutations, although full data will be needed to back this up. The company plans to present the results at an upcoming medical meeting.
The only other PARP inhibitor in active development for HSPC, according to OncologyPipeline is AstraZeneca’s PARP1-selective saruparib. That project is in the phase 3 Evopar-Prostate01 study, evaluating a combo with investigator’s choice of novel hormonal agent (Zytiga, Xtandi or the like) versus a novel hormonal agent alone.
That study, which is enrolling both HRRm and non-HRRm patients, started in 2023, but results aren’t due until after 2027, Astra disclosed in its fourth-quarter earnings presentation.
PARP inhibitors in hormone-sensitive prostate cancer
| Product/project | Description | Company | Trial | Note |
|---|---|---|---|---|
| Akeega (niraparib + abiraterone acetate FDC) | PARP inhibitor + AR antagonist | J&J | Ph3 Amplitude | FDA approved Dec 2025, + prednisone, for BRCA2m mHSPC |
| Talzenna | PARP inhibitor | Pfizer | Ph3 Talapro-3, + Xtandi | Toplined positive for rPFS Mar 2026 |
| Saruparib | PARP1 inhibitor | AstraZeneca | Ph3 EvoPAR-Prostate01, + novel hormonal agent | Data due >2027 |
Source: OncologyPipeline.
Meanwhile, the Talzenna/Xtandi combo is now heading to regulators for HSPC, although Pfizer didn’t give any details on filing timelines.
Talapro-3 compared the doublet versus Xtandi alone (a current HSPC treatment option), with a primary endpoint of radiologic progression-free survival. Here, Talzenna plus Xtandi showed a “statistically significant and clinically meaningful benefit”, with results “markedly” exceeding the pre-specified target hazard ratio of 0.63, Pfizer said.
The group also highlighted a “strong trend” towards improvement in the key secondary endpoint of overall survival.
Alterations in DNA damage repair genes such as the HRR genes are found in around 25% of metastatic prostate cancers, Pfizer estimates. But efforts to move beyond this niche have fallen flat.
Talzenna plus Xtandi was approved in the US for HRR gene-mutated metastatic CRPC in June 2023, but last year Pfizer was knocked back by the FDA in CRPC all comers. Crucially, the Talapro-2 trial’s all-comers benefit was driven by HRR-altered patients.
Talzenna/Xtandi already had an all-comers EU label in CRPC. The drug isn’t a huge seller, bringing in $182m in 2025, but a HSPC label, if approved, could provide a boost.
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