An overview of first-line talazoparib plus enzalutamide for metastatic castration-resistant prostate cancer.
In the prior PROpel trial, which was published in NEJM Evid 2022; researchers demonstrated the effectiveness of pairing the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib with the androgen receptor inhibitor (ARI) abiraterone for patients dealing with metastatic castration-resistant prostate cancer (mCRPC) during their initial treatment phase. This advantageous outcome was observed irrespective of the presence of mutations in homologous recombination repair (HRR) genes, including BRCA1/2 mutations, although the benefit was more pronounced in individuals with HRR deficiencies. HRR gene alterations are identified in roughly 25% of patients.
In a parallel endeavor, an industry-sponsored, international, randomized, double-blind, placebo-controlled phase 3 trial named TALAPRO-2 was undertaken to evaluate the impact of introducing the PARP inhibitor talazoparib into the standard enzalutamide treatment for androgen receptor inhibition (ARI) during the initial treatment stage. The investigation was segregated into two segments: one encompassing all patients (Cohort 1) and another concentrating exclusively on those exhibiting HRR deficiencies (Cohort 2). This particular study report focuses on Cohort 1, encompassing 805 patients grappling with mCRPC. The median age of this patient group was 71 years, with 64% to 67% showcasing a performance status of 0. Approximately 20% to 21% exhibited HRR deficiencies, 7% to 8% carried BRCA1/2 mutations, and 5% to 6% had previously undergone abiraterone treatment.
Following a median tracking period of about 25 months, the median duration of radiographic progression-free survival was prolonged for a combination of talazoparib and enzalutamide in comparison to those who solely received enzalutamide. The calculated hazard ratio stood at 0.63, indicating a noteworthy enhancement resulting from the combination of talazoparib and enzalutamide (P < 0.0001). The combination arm was noted to have significantly higher incidence of anemia.
Following the endorsement of the olaparib and abiraterone combination for men with BRCA-mutated mCRPC by an FDA Oncology Drugs Advisory Committee panel, the FDA subsequently granted approval. Presenting data from Cohort 2 of the TALAPRO-2 study at the recent American Society of Clinical Oncology (ASCO) meeting further substantiated the substantial efficacy of the talazoparib plus enzalutamide combination for patients with HRR deficiencies.
Reference:
Agarwal N et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): A randomized, placebo-controlled, phase 3 trial. Lancet. 2023 Jul 22;402(10398):291-303. doi: 10.1016/S0140-6736(23)01055-3. Epub 2023 Jun 4.
