Pfizer is eyeing an earlier use of its PARP inhibitor Talzenna after a positive phase 3 trial in metastatic hormone-sensitive prostate cancer (mHSPC).
The phase 3 Talapro-3 trial met its primary endpoint by showing the combo of Talzenna and Pfizer and Astellas’ prostate cancer drug Xtandi significantly reduced the risk of tumor progression or death compared with Xtandi and placebo. This was in patients with homologous recombination repair (HRR) gene-mutated mHSPC, Pfizer announced in a Thursday, March 19 release.
The radiographic progression-free survival result “markedly exceeded” the prespecified target of a 37% improvement, according to the company. Pfizer described the efficacy as “consistent” between BRCA-mutated and non-BRCA-mutated subgroups.
The interim analysis also revealed what Pfizer called a “strong trend” toward improved overall survival, a key secondary endpoint. The New York pharma also cited benefits in other secondary endpoints such as overall response rate, duration of response and time to PSA progression.
With the positive readout, Pfizer said it plans to discuss these results with global regulators for potential submissions for approvals.
HRR mutations are found in about 25% of metastatic prostate cancers and are associated with a worse prognosis, Pfizer’s chief oncology officer, Jeff Legos, Ph.D., noted in a statement. Despite existing treatment, 50% to 65% of patients with metastatic castration-sensitive prostate cancer progress to metastatic castration-resistant prostate cancer (mCRPC) within two years, according to Pfizer.
As the Talzenna-Xtandi combo is already approved in HRR-mutated mCRPC, the “unprecedented results” from Talapro-3 show its potential to benefit patients earlier in the disease course, Legos added.
The Talapro-3 readout gives Pfizer another opportunity to expand the reach of Talzenna after a recent FDA snub in a broader mCRPC population.
In May 2025, an FDA advisory committee voted unanimously against the approval of Talzenna and Xtandi for mCRPC patients without HRR gene mutations, based on data from the phase 3 Talapro-2 trial. The FDA, after questioning the validity of Talapro-2’s findings in the non-mutant subgroup, followed the panel’s recommendation in June with a label update for Talzenna to only add new overall survival data in its existing HRR-mutated mCRPC indication.
Before the latest Talzenna readout, the FDA had approved Johnson & Johnson’s two-drug PARP combo Akeega in BRCA2-mutated mHSPC. Talzenna could be the first PARP inhibitor to enter a broader HRR-mutant mHSPC setting.
Compared with Xtandi, the leading androgen receptor inhibitor, Talzenna is a relatively small product within Pfizer’s oncology portfolio and the PARP inhibitor class. In 2025, Talzenna generated $182 million in sales, up 55.6% year on year.
Xtandi received its mHSPC nod from the FDA in 2019 and then became the first androgen receptor inhibitor approved in nonmetastatic castration-sensitive prostate cancer in 2023.
Besides Talzenna, Pfizer is also pairing Xtandi with its experimental EZH2 inhibitor mevrometostat in mHSPC in the phase 3 Mevpro-3 trial. The phase 3 Mevpro-1 trial for the drug and Xtandi in mCRPC following treatment with J&J’s Zytiga is expected to read out this year.
Editor's Note: The story has been corrected to reflect that J&J's Akeega is already FDA-approved in an mHSPC subset.