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e16547 Background: Platinum-based chemotherapy (PBC) has been the standard of care for first-line (1L) locally advanced/metastatic urothelial carcinoma (la/mUC). This systematic literature review (SLR) and network meta-analysis (NMA) analyzed the latest 1L clinical trial data to assess the comparative efficacy of the novel regimen enfortumab vedotin in combination with pembrolizumab (EV+P) against PBC and other approved and investigational 1L regimens for patients with la/mUC. Methods: English language publications (1/2000-10/2023) and congress presentations (1/2015-10/2023) of Phase 2 and 3 clinical trials assessing efficacy and safety of 1L therapies in la/mUC were identified in the SLR. Studies were categorized as: mixed eligibility (cisplatin cis-eligible and -ineligible), cis-eligible, and cis-ineligible. An NMA assessed comparative efficacy of EV+P to guideline-recommended therapies and emerging therapies with demonstrated survival benefit. 1L switch maintenance therapies were not included due to differences in study design. Comparative efficacy for overall survival (OS) was assessed under a Bayesian framework assuming constant hazard ratio (HR). Results: The SLR identified 69 unique studies, 2 of which demonstrated survival benefit over PBC (EV-302 and CheckMate-901 substudy). Across all mixed eligibility studies, median OS for PBC ranged from 12.1-16.1 months. Five studies were included in the NMA (3 mixed eligibility, 4 cis-eligible, 3 cis-ineligible). NMA results for the mixed eligibility network showed that EV+P improved OS over all comparator regimens (HR 0.47-0.51; Table). In the cis-eligible network, EV+P subgroup analysis showed improved OS over nivolumab+PBC (HR 0.68 95% CI 0.47, 0.98) and PBC (HR 0.53 95% CI 0.39, 0.72) and numerically improved OS over ddMVAC (HR 0.76 95% CI 0.48, 1.20). In the cis-ineligible network, EV+P subgroup analysis showed improved OS over all comparator regimens (HR range 0.43-0.52). Limitations include few studies contributing to the networks and heterogeneity in patient populations. Conclusions: EV+P is the only regimen shown to improve survival compared with PBC regardless of cisplatin eligibility. This indirect comparison suggests that EV+P has a favorable survival benefit compared with other approved and investigational 1L regimens in patients with previously untreated la/mUC. Table: see text
Bloudek et al. (Sat,) studied this question.