The phase 3 TALAPRO-2 study met the primary end point of radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer with or without homologous recombination repair gene mutations following treatment with a combination of talazoparib and enzalutamide.
Talazoparib (Talzenna) in combination with enzalutamide (Xtandi) produced clinically meaningful improvements in radiographic progression-free survival (rPFS) compared with placebo and enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) regardless of the presence of homologous recombination repair (HRR) gene mutations, according to a press release from Pfizer on the phase 3 TALAPRO-2 study (NCT03395197).
In terms of rPFS, talazoparib plus enzalutamide exceeded the trial’s pre-specified hazard ratio (HR) of 0.696. Trends towards benefit were observed in the combination arm across secondary end points such as overall survival (OS), investigator-assessed rPFS, prostate specific antigen (PSA) response, time to PSA progression, and overall response rate (ORR), although these data were immature during the time of analysis. During the TALAPRO-2 study’s topline analysis, the safety profile of talazoparib and enzalutamide was found to be generally consistent with the known profiles of each agent.
“We are very pleased with the strong findings from TALAPRO-2, and although no definitive conclusions can be made across trials, the rPFS appears to be the longest observed in a randomized trial in this setting,” Chris Boshoff, MD, PhD, chief development officer, Oncology and Rare Disease, Global Product Development at Pfizer, said in the press release. “These data highlight the potential for [talazoparib] in combination with [enzalutamide,] if approved, to become a new standard of care for mCRPC, irrespective of HRR gene mutation status. We look forward to discussing these data with global health authorities.”
The ongoing, two-part TALAPRO-2 study enrolled a total of 1095 patients across multiple centers from the U.S, Canada, Europe, South America, and the Asia-Pacific region. The first part of the study was a non-randomized safety assessment of the appropriate starting dose of talazoparib in combination with enzalutamide, and the second part was a randomized, double-blind, placebo-controlled trial exploring the efficacy of the combination regimen compared with placebo and enzalutamide in patients with mCRPC. The first patient cohort included all-comers (n = 750) and the second consisted of patients with HRR mutations (n = 380).
Eligible patients who had undergone bilateral orchiectomy or received androgen deprivation therapy (ADT) were randomly assigned to receive either 0.5 mg of talazoparib per day and a 160 mg daily dose of enzalutamide or placebo plus 160 mg of enzalutamide daily.
Additional inclusion criteria for patients 18 years and older included histologically confirmed adenocarcinoma of the prostate, asymptomatic or mildly symptomatic mCRPC, metastatic disease in bone documented on bone scan or with soft tissue documented on a CT/MRI scan, and an ECOG performance status of 1 or 0. Patients were excluded from the trial if they had any previous systemic treatment in the non-metastatic and metastatic setting; prior treatment second-generation androgen receptor inhibitors, PARP inhibitors, cyclophosphamide, or mitoxantrone for prostate cancer; or any history of disease progression after platinum-based chemotherapy within 6 months of the last dose.
As a supplement to this study, the phase 3 TALAPRO-3 trial (NCT04821622) is further investigating the clinical use of the talazoparib and enzalutamide combination in a population of patients with DNA damage repair–mutated metastatic castration-sensitive prostate cancer.
Pfizer announces positive topline results from phase 3 TALAPRO-2 trial. News release. Pfizer. October 4, 2022. Accessed October 4, 2022. https://bit.ly/3e5A99S