Matching-adjusted Indirect Comparison of Talazoparib Plus Enzalutamide Versus Abiraterone Acetate and Docetaxel in MCRPC

Aims: The absence of direct comparisons between talazoparib plus enzalutamide (TALA+ENZA) and current standard of care hinders evaluating their relative efficacy for first-line (1 L) metastatic castration resistant prostate cancer (mCRPC). This study aimed to compare TALA+ENZA (TALAPRO-2) to abiraterone acetate plus prednisone (AAP) (COU-AA-302) and docetaxel (TAX 327) using a matching-adjusted indirect treatment comparison (MAIC).

Methods: A systematic literature review using the Ovid® interface was performed to identify relevant evidence. Patient-level data from TALAPRO-2 and published data from COU-AA-302 and TAX 327 were used to match populations on clinically relevant confounders. The MAICs were conducted for radiographic progression-free survival (rPFS), overall survival (OS), objective response rate (ORR), along with additional efficacy outcomes.

Results: In all-comers, TALA+ENZA statistically significantly prolonged rPFS (HR: 0.256; 95% confidence interval [CI]: 0.183, 0.359;  < 0.0001), OS (HR: 0.557; 0.405, 0.766;  = 0.0003), and improved ORR (OR: 3.924; 2.017, 7.634;  = 0001) versus AAP. In all-comers, TALA+ENZA significantly prolonged OS (HR: 0.446; 0.316, 0.631;  < 0.0001) and improved ORR (OR: 13.081; 5.757, 29.721;  < 0.0001) versus docetaxel. All other efficacy outcomes statistically favored TALA+ENZA.

Conclusions: These results suggest TALA+ENZA improves clinical outcomes relative to AAP and docetaxel in the 1 L mCRPC all-comers population.