Talazoparib/Enzalutamide Combo Offers Significant Survival Benefits in Prostate Cancer
According to findings from the TALAPRO-2 study, the combination led to significant and meaningful improvements in overall survival vs enzalutamide monotherapy.
PC-3 human prostate cancer cells: © heitipaves - stock.adobe.com
The PARP inhibitor talazoparib (Talzenna) plus enzalutamide (Xtandi), an androgen receptor pathway inhibitor (ARPI), led to statistically significant and meaningful improvements in overall survival (OS) in all-comers as well as patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC), according to data from the phase 3 TALAPRO-2 study (NCT03395197).1
“These overall survival results indicate potentially practice-changing efficacy for [talazoparib] in combination with [enzalutamide] for [patients] with metastatic castration-resistant prostate cancer,” said Neeraj Agarwal, MD, FASCO, professor and presidential endowed chair of cancer research at Huntsman Cancer Institute, University of Utah, and global lead investigator for TALAPRO-2, said in a press release. “Metastatic castration-resistant prostate cancer 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.”
Full results from this analysis will be presented at an upcoming medical meeting and shared with global regulatory authorities.
In June 2023, the FDA approved the talazoparib/enzalutamide combination for the treatment of HRR gene-mutant mCRPC, supported by data from TALAPRO-2.2 The combination led to a 55% reduction in the risk of disease progression or death (HR, 0.45; 95% CI, 0.33-0.61; P <.0001).2,3 The median radiographic progression-free survival (rPFS) was not reached (NR, 95% CI, 27.5 months-NR) with talazoparib and enzalutamide vs 21.9 months (range, 16.6-25.1) with placebo plus enzalutamide.3
Regarding safety, the most common treatment-emergent adverse effects (AEs) with talazoparib were anemia, neutropenia, and fatigue, while the most common grade 3 to 4 AE was anemia, which improved after dose reduction.
About TALAPRO-2
The phase 3, double-blind, placebo-controlled TALAPRO-2 trial randomized 805 patients to receive talazoparib 0.5 mg or placebo and enzalutamide 160 mg per day. Randomization was stratified by HRR gene alteration status.The study’s primary end point was rPFS.3,4
Male patients aged 18 and older were eligible to enroll in the study if they had progressive disease at study entry, an ECOG performance status of 1 or lower, and a life expectancy of at least 12 months. Those who had been previously treated with a second-generation ARPI, PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer; clinically significant cardiovascular disease; or significant renal or hepatic dysfunction were ineligible for participation.4
