Indirect comparisons suggest that the combination of talazoparib and enzalutamide may offer superior clinical outcomes compared to other PARP inhibitor combinations in the first-line treatment of metastatic castration-resistant prostate cancer (mCRPC). The matching-adjusted indirect comparison (MAIC) analyzed data from the Phase 3 TALAPRO-2 trial and compared it with results from the PROpel and MAGNITUDE trials.
The study, published in Nature, used individual patient data (IPD) from the TALAPRO-2 trial and aggregate data from the PROpel and MAGNITUDE trials to conduct unanchored MAICs. This approach allowed researchers to estimate the relative treatment effects of talazoparib plus enzalutamide (TALA+ENZA) versus olaparib plus abiraterone acetate (OLAP+AAP), and niraparib plus abiraterone acetate (NIRA+AAP).
Methodology
The systematic literature review identified relevant randomized controlled trials (RCTs) evaluating first-line treatments in men with asymptomatic or mildly symptomatic mCRPC. Databases searched included Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. Key clinical conference websites and grey literature sources were also hand-searched. The primary outcome assessed was radiographic progression-free survival (rPFS) as assessed by blinded independent central review (BICR), with overall survival (OS) as a key secondary outcome. Other outcomes included PFS on the next line of therapy (PFS2), time to prostate-specific antigen (PSA) progression, time to cytotoxic chemotherapy initiation, PSA response, and objective response rate (ORR).
Key Findings
The MAIC analysis revealed potential benefits of TALA+ENZA over OLAP+AAP in the all-comer population. Furthermore, in patients with HRR-deficient mCRPC, TALA+ENZA showed potential advantages over NIRA+AAP. These findings suggest that the choice of PARP inhibitor combination may impact treatment outcomes in mCRPC.
Implications for Clinical Practice
These indirect comparisons provide valuable insights for clinicians treating mCRPC. While direct head-to-head trials are needed to confirm these findings, the current analysis suggests that talazoparib plus enzalutamide may be a preferred first-line treatment option, particularly in patients with HRR deficiency. The study underscores the importance of considering individual patient characteristics and genomic profiles when selecting the most appropriate therapy for mCRPC.
