The US Food and Drug Administration (FDA) has expanded the approval of Pfizer’s TALZENNA (talazoparib), in combination with XTANDI (enzalutamide), to treat men with metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer with homologous recombination repair (HRR) gene mutations, including BRCA and non-BRCA mutations.
mAPMN/S prostate cancer is also known as metastatic hormone-sensitive prostate cancer (mHSPC).
The expanded approval makes TALZENNA, an oral poly ADP-ribose polymerase (PARP) inhibitor, plus XTANDI, an androgen receptor pathway inhibitor (ARPI), available at an earlier stage of the disease. The combination offers a treatment option that could delay disease progression at a critical stage when more patients may experience greater benefit.
“Today’s approval of TALZENNA plus XTANDI builds on its established role as a standard-of-care option for men with advanced prostate cancer,” said Aamir Malik, executive vice president and chief US commercial officer, Pfizer.
“Moving this targeted therapy into the androgen pathway modulation-naïve or -sensitive setting further reflects our commitment to men with HRR-mutated metastatic prostate cancer, providing a new option at a stage where it may have a greater impact to delay progression,” he added.
TALZENNA plus XTANDI was first approved in the US in 2023 for men with metastatic androgen pathway modulation-resistant (mAPMR) prostate cancer with HRR gene mutations, also known as HRR-mutated metastatic castration-resistant prostate cancer (mCRPC).
The European Commission approved the combination in January 2024 for adults with mCRPC for whom chemotherapy is not clinically indicated. TALZENNA in combination with XTANDI is approved in more than 60 countries, although indications vary by country.
The FDA reviewed the application under its Priority Review programme. The expanded approval was supported by results from the Phase 3 TALAPRO-3 study.
The trial showed that TALZENNA plus XTANDI reduced the risk of radiographic disease progression or death by 52% compared with placebo plus XTANDI in patients with mAPMN/S prostate cancer and HRR gene mutations. An estimated 77% of patients receiving the combination remained progression-free at three years.
Consistent benefits were observed in patients with both BRCA and non-BRCA HRR gene mutations.
“This approval represents a critical advancement for patients with newly diagnosed metastatic prostate cancer with HRR gene mutations, who face a more aggressive disease, worse prognosis, and limited treatment options,” said Neeraj Agarwal, global lead investigator for TALAPRO-3.
Agarwal is co-director of the Prostate Cancer Program at the Harvard Cancer Consortium and a faculty medical oncologist at Dana-Farber Cancer Institute.
“In the TALAPRO-3 trial, clinical benefits were consistent for patients with BRCA and non-BRCA HRR gene mutations, addressing a long-standing unmet need – and reinforcing the importance of biomarker testing at the time of diagnosis,” Agarwal added.
TALZENNA was initially approved in the US, the European Union and other regions as a monotherapy for adults with deleterious or suspected deleterious gBRCAm HER2-negative locally advanced or metastatic breast cancer.
XTANDI has received regulatory approval in several countries for the treatment of prostate cancer across multiple settings, including mHSPC, mCRPC, non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). It is approved for one or more of these indications in more than 80 countries, including the US, the European Union and Japan.
XTANDI is jointly developed and commercialised by Pfizer and Astellas in the US.
