FDA Approves Talzenna-Xtandi Combo for Subset of Patients With Prostate Cancer

Patients with HRR gene mutations treated with Talzenna and Xtandi had a significant improvement in radiographic progression-free survival.

The Food and Drug Administration (FDA) approved Talzenna (talazoparib) with Xtandi (enzalutamide) for the treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer.

This FDA approval was based on findings from the TALAPRO-2 trial, which included 399 patients with HRR gene-mutated metastatic castration-resistant prostate cancer, according to a release from the Agency. Patients randomly received Xtandi with either Talzenna or placebo.

Findings from the trial demonstrated that patients with HRR gene mutations treated with Talzenna and Xtandi had a significant improvement in radiographic progression-free survival (the time during and after treatment when a patient with cancer lives without disease worsening) compared with those treated with placebo plus Xtandi, according to the release. In particular, progression-free survival was not reached in the Talzenna-Xtandi group — meaning that at least half of the patients in the trial were alive without progression when this outcome was assessed — compared with 13.8 months in the placebo-Xtandi group.

“The FDA’s approval of the (Talzenna) and (Xtandi) 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,” Dr. Neeraj Agarwal, professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute at the University of Utah and global lead investigator for TALAPRO-2, said in a press release from Pfizer, the manufacturer of Talzenna.

To be considered for the trial, patients were required to have previously undergone an orchiectomy (surgical removal of one or both testicles) or have received gonadotropin-releasing hormone analogs.

The following HRR genes were assessed in this trial, according to the release: ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2 and or RAD51C.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” Agarwal said. “Therefore, new first-line treatment options are needed to reduce the risk of disease progression or death. For patients with (metastatic castration-resistant prostate cancer) harboring HRR genetic alterations, outcomes are even worse.”

The most common side effects, which occurred in at least 10% of patients in the trial, included laboratory abnormalities such as decreased neutrophils (a type of white blood cells), fatigue, nausea, decreased appetite, fractures, dizziness and altered taste, according to the FDA’s statement. Of all the patients with metastatic castration-resistant prostate cancer treated with the Talzenna-Xtandi combination, 39% required a blood transfusion, which included 22% of them who needed multiple transfusions. Two patients in the trial were diagnosed with acute myeloid leukemia or myelodysplastic syndrome.

“As a global standard of care, Xtandi has shown efficacy in three 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,” Angela Hwang, chief commercial officer and president of the global biopharmaceuticals business at Pfizer, said in the 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.”

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