Presentation (CTI)

OBJECTIVES: Although multiple treatment options exist for mCSPC, limited evidence evaluates patients with HRR gene alterations, and even fewer studies assess benefits directly using currently approved therapies. In the absence of head-to-head evidence, ITCs offer a pragmatic method to estimate comparative treatment effects. However, rigorous assessment of similarity, homogeneity, and consistency is essential to ensure transparency, validity, and appropriate interpretation for health technology assessment (HTA) decision-making. Accordingly, an SLR and feasibility assessment were conducted to evaluate the appropriateness of ITCs for estimating relative treatment effects in HRR-deficient mCSPC.
METHODS: Clinical trials evaluating treatments for mCSPC were identified through a SLR. Searches were conducted in Ovid® from inception to January 2026 and supplemented with grey literature. Identified trials were qualitatively assessed for ITC feasibility based on trial design, eligibility criteria, baseline patient characteristics, outcome definitions, and network connectivity. Outcomes of interest included radiographic progression‑free survival (rPFS) and overall survival (OS).
RESULTS: Twenty‑six trials (19 randomized controlled and 7 single‑arm trials) were included. Only four trials enrolled confirmed HRR‑deficient populations. Two were single‑arm trials with small sample sizes (≤30 patients), and the remaining two randomized trials (TALAPRO‑3 and AMPLITUDE) lacked a common comparator, resulting in a disconnected evidence network. Consequently, standard anchored ITCs were not feasible. Unanchored matching‑adjusted indirect comparisons or simulated treatment comparisons between TALAPRO‑3 and AMPLITUDE were considered feasible for rPFS and OS; however, full alignment on Eastern Cooperative Oncology Group status, prior treatment exposure, and HRR genes will not be possible.
CONCLUSIONS: ITCs in HRR-deficient mCSPC face methodological challenges due to substantial trial heterogeneity in the current evidence base, complicating their conduct and interpretation. These limitations underscore the need for transparent, robust approaches, including patient level-adjusted or external control analyses, and highlight priorities for future evidence generation and methodological innovation. Payers, decision makers, and HTA bodies should therefore interpret unadjusted ITCs with caution.