Talazoparib Plus Enzalutamide Improves OS in mCRPC

Treatment with talazoparib (Talzenna) plus enzalutamide (Xtandi) led to an improvement in overall survival (OS) compared with enzalutamide monotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC), according to updated data from the phase 3 TALAPRO-2 trial (NCT03395197).¹

Findings announced by Pfizer showed that the OS improvement was observed in all-comers enrolled in cohort 1 and in patients harboring homologous recombination repair (HRR) gene mutations enrolled in cohort 2.

Full data will be submitted for presentation at an upcoming medical conference and shared with global health authorities to potentially support for approved label expansion for the combination.

“These OS results indicate potentially practice-changing efficacy for [talazoparib] in combination with [enzalutamide] for men with mCRPC,” Neeraj Agarwal, MD, FASCO, professor and presidential endowed chair of cancer research at Huntsman Cancer Institute at the University of Utah in Salt Lake City and global lead investigator for TALAPRO-2, stated in a news release. “mCRPC is the most advanced and aggressive stage of the disease, and the TALAPRO-2 results provide much-needed hope to patients who remain in high unmet need for effective treatment options.”

In June 2023, the FDA approved talazoparib plus enzalutamide for the treatment of patients with HRR gene–mutated mCRPC, based on prior findings from TALAPRO-2.²

Previously reported data showed patients harboring HRR gene mutations treated with the combination experienced a median radiographic progression-free survival (rPFS) that was not reached (NR) compared with 13.8 months for those given enzalutamide alone (HR, 0.45; 95% CI, 0.33-0.61; P < .0001).

Data published in The Lancet in 2023 showed that among the overall population, talazoparib plus enzalutamide (n = 402) elicited a median rPFS that was NR (95% CI, 27.5-NR) vs 21.9 months (95% CI, 16.6-25.1) for enzalutamide alone (n = 403; HR, 0.63; 95% CI, 0.51-0.78; P < .0001).³

In the news release, Pfizer reported that the clinically meaningful improvement in rPFS was maintained in both cohort 1 and cohort 2.¹

The double-blind TALAPRO-2 trial enrolled patients at least 18 years of age (or at least 20 years of age in Japan) with asymptomatic or mildly symptomatic mCRPC who were receiving ongoing androgen deprivation therapy.3 Key inclusion criteria consisted of an ECOG performance status of 0 or 1, progressive disease at study entry, adequate bone marrow function, and no prior life-prolonging treatment for CRPC or mCRPC. Prior treatment with docetaxel and abiraterone acetate (Zytiga) in the castration-sensitive setting was allowed.

Patients were prospectively assessed for HRR status and randomly assigned 1:1 to receive talazorparib at 0.5 mg once per day plus enzalutamide at 160 mg once per day; or placebo plus the same dosage of enzalutamide. Cohort 1 included all-comers, irrespective of HRR status. After enrollment concluded in cohort 1, cohort 2 was restricted to patients harboring HRR gene alterations.

The trial’s primary end point was rPFS per RECIST 1.1 criteria as assessed by blinded independent central review. Key secondary end points included OS, investigator-assessed rPFS, objective response rate, and safety.

Updated safety data in the final analysis were consistent with the known safety profiles of talazoparib and enzalutamide.¹

References

1. Pfizer’s Talzenna in combination with Xtandi prolongs overall survival in phase 3 TALAPRO-2 trial. News release. Pfizer. October 10, 2024. Accessed October 10, 2024. https://investors.pfizer.com/Investors/News/news-details/2024/Pfizers-TALZENNA-in-Combination-with-XTANDI-Prolongs-Overall-Survival-in-Phase-3-TALAPRO-2-Trial/default.aspx
2. FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. FDA. June 20, 2023. Accessed October 10, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-enzalutamide-hrr-gene-mutated-metastatic-castration-resistant-prostate
3. Agarwal N, Azad AA, Carles J, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023;402(10398):291-303. doi:10.1016/S0140-6736(23)01055-3