In prostate cancer, Pfizer’s Talzenna already holds the broadest FDA approval within the PARP inhibitor class. Now, with new data indicating the drug could prolong patients’ lives, the company is targeting an even wider label.
Adding Talzenna to Pfizer’s Astellas-partnered Xtandi significantly improved the life expectancy of patients with metastatic castration-resistant prostate cancer (mCPRC) regardless of the tumor’s mutation status, Pfizer said Thursday. The overall survival showing, from the final analysis of the phase 3 TALAPRO-2 trial, was statistically significant and clinically meaningful, the company said.
Armed with the updated data, Pfizer said it plans to share the results with global regulatory authorities to potential apply for a label expansion to cover a broad patient population with mCRPC.
In June 2023, the Talzenna-Xtandi combo received the FDA’s blessing to treat mCPRC that has homologous recombination repair (HRR) gene mutations.
That label is the broadest of an mCRPC indication among PARP inhibitors; AstraZeneca and Merck & Co.’s Lynparza—used in combination with Johnson & Johnson’s Zytiga—and J&J’s fixed-dose combo Akeega are only allowed in BRCA mutations, which are just part of the HRR alteration family.
With TALAPRO-2, Talzenna is now the first PARP inhibitor to be able to significantly improve survival in patients with mCRPC regardless of mutation status, Pfizer’s oncology chief development officer, Roger Dansey, M.D., said in a statement Thursday.
Neerja Agarawal, M.D., from the University of Utah and lead investigator for TALAPRO-2, said the results indicate potential “practice-changing efficacy,” according to a statement facilitated by Pfizer.
Talzenna got its HRR-mutation nod based on TALAPRO-2 showing its addition to Xtandi could lower the risk of progression or death by 55% in those patients. At that time, the Talzenna-Xtandi combo also showed a 37% progression-free survival improvement versus Xtandi alone in a cohort that includes patients both with and without HRR mutations.
PARP inhibitors are expected to work best in tumors with BRCA mutations but not as much in other HRR mutations, with the least potential in those without HRR abnormalities.
In the phase 3 MAGNITUDE trial, J&J’s Akeega—a combination of niraparib (GSK’s Zejula) and Zytiga—didn’t show any benefit in mCRPC patients without HRR mutations. Lynparza’s mCRPC nod was also limited to BRCA mutations, because the FDA found those patients drove the benefit seen in the overall population enrolled in the phase 3 PROpel trial.
Now, the key question for Pfizer’s updated TALAPRO-2 data is whether patients without HRR mutations saw any overall survival benefit. A Pfizer spokesperson said the company will share more details later.
During a previous interim analysis of TALAPRO-2, Talzenna showed a preliminary trend toward a 31% improvement in overall survival in HRR-mutated cases. At that time, only about one-fourth of the HRR-mutated population had passed away.
Talzenna is still a small asset in Pfizer’s oncology portfolio. The drug’s sales in the first half of 2024 were just $55 million, compared with $22 million during the same period last year. The company’s total oncology haul during the six months was $7.5 billion. Unlike Lynparza, Zejula and pharma&’s Rubraca, Talzenna doesn’t have an ovarian cancer indication, which has been the biggest field for PARP inhibitors.