FDA Approves Talazoparib, Enzalutamide Combination for Metastatic Castration-Resistant Prostate Cancer


Clinical trial results showed that the combination significantly improved radiographic progression-free survival compared with enzalutamide monotherapy for homologous recombination repair gene–mutated metastatic castration-resistant prostate cancer.

The FDA has approved talazoparib (Talzenna) plus enzalutamide (Xtandi) for the treatment of patients with homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC).1

Conceptual image for prostate cancer treatment, 3D illustration showing destruction of a tumor inside prostate gland. Credit: Dr_Microbe - stock.adobe.com

Credit: Dr_Microbe - stock.adobe.com

The FDA approved the combination based on results from the phase 3 TALAPRO-2 trial (NCT03395197), which showed that adding talazoparib to enzalutamide significantly improved radiographic progression-free survival (rPFS) compared with enzalutamide monotherapy in patients with HRR mCRPC.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy. Therefore, new first-line treatment options are needed to reduce the risk of disease progression or death. For patients with mCRPC harboring HRR genetic alterations, outcomes are even worse,” global lead investigator for TALAPRO-2 Neeraj Agarwal, MD, FASCO, professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, said in a press release. “The FDA’s approval of the talazoparib and enzalutamide combination is based on the findings from the pivotal TALAPRO-2 study, which demonstrated statistically significant and clinically meaningful reductions in the risk of progression or death among HRR gene-mutated tumors in patients with metastatic castration-resistant prostate cancer. It represents a treatment option deserving of excitement and attention.”1

Talazoparib is an oral poly ADP-ribose polymerase (PARP) inhibitor. Preclinical studies demonstrated that talazoparib blocks PARP enzyme activity and traps PARP at the site of DNA damage, resulting in decreased growth of cancer cells and cancer cell death.1

TALAPRO-2 was a double-blind, placebo-controlled, multicohort trial that included patients with HRR gene–mutated mCRPC (n = 399) who were required to have an ECOG performance status of 0 or 1.2 Patients enrolled also needed to have progressed on previous androgen deprivation therapy. Prior therapy with docetaxel or a CYP17 inhibitor for metastatic castration-sensitive disease was permitted. 

Mutation status was determined by using solid tumor tissue or next-generation sequencing assays, with participants required to have a mutation in at least 1 of 12 genes involved in the HRR pathway: ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C.2

The primary outcome was rPFS, with the additional secondary outcome of overall survival (OS). According to the findings, patients randomized to talazoparib in combination with enzalutamide experienced a statistically significant improvement in rPFS compared with placebo at the pre-specified interim analysis. Consistent rPFS results were observed regardless of whether patients received a prior CYP17 inhibitor or docetaxel. The OS data were not mature at the time of the rPFS analysis and 24% of patients had died.2

Safety of talazoparib plus enzalutamide in the TALAPRO-2 trial was generally consistent with the known safety profile of both drugs. Serious adverse events (AEs) occurred in 30% of patients treated with the combination and serious AEs were reported in >2% of patients, which included anemia (9%) and fracture (3%). Discontinuation occurred in 10% of patients.1

“As a global standard of care, Xtandi has shown efficacy in 3 types of prostate cancer, and the addition of Talzenna demonstrated significant improvements in delaying or preventing radiographic progression-free survival or death in patients with this type of advanced prostate cancer,” said Angela Hwang, MBA, chief commercial officer and president of Global Biopharmaceuticals Business at Pfizer, in the press release. “With today’s FDA approval of Talzenna plus Xtandi, we are proud to be able to offer this potentially practice-changing treatment to patients and add to their options in managing this aggressive disease.”1

Talazoparib is already approved for the treatment of adult patients with deleterious or suspected deleterious germline BRCA–mutated human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer.1


  1. Pfizer’s Talzenna in Combination with Xtandi Receives US FDA Approval. News release. Pfizer. June 20, 2023. Accessed June 21, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-talzennar-combination-xtandir-receives-us-fda
  2. Talzenna. Prescribing Information. FDA. 2018. Revised June 2023. Accessed June 21, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/211651s010lbl.pdf
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