Matching-Adjusted Indirect Comparisons of Gemcitabine Intravesical System vs Novel Agents in Bacillus Calmette-Guérin–Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer

Background: Several novel agents, including gemcitabine intravesical system (gem-iDRS), pembrolizumab, nadofaragene firadenovec-vncg (nadofaragene), and nogapendekin alfa inbakicept-pmln (NAI)+ Bacillus Calmette-Guérin (BCG), have been investigated in BCG-unresponsive high-risk non–muscle-invasive bladder cancer (HRNMIBC). Because comparative trials are unavailable, matching-adjusted indirect comparisons (MAICs) were performed to assess the relative efficacy of gem-iDRS vs these novel agents. Methods: Novel agents for BCG-unresponsive HR NMIBC with US prescribing information (USPI) were used to conduct unanchored MAICs. Individual patient-level data for gem-iDRS monotherapy from SunRISe-1 (cohorts 2 and 4) and comparator data from the USPI's and primary publications of KEYNOTE-057, CS-003, and QUILT 3.032 were used. A complete response (CR) rate at any time and at 12 months, the CR rate at first disease assessment for the carcinoma in situ (CIS) cohort, and the disease-free survival rate overall and at 12 months, for the papillary-only cohort were compared. Results: After weighting, baseline characteristics were similar across trials. In the CIS cohort, gem-iDRS conferred significantly higher CR rates at any time vs all 3 agents, a higher CR rate at first disease assessment vs NAI + BCG, and a higher CR rate at 12 months vs pembrolizumab and nadofaragene; P < .05 for all. For the papillary-only cohort, gem-iDRS reduced the risk of high-grade recurrence, progression, or death by 64% and significantly improved 12-month DFS by 28.9% compared with pembrolizumab, P < .05 for both. Conclusions: Based on the MAIC analyses, gem-iDRS provides significant clinical benefit over novel agents for the treatment of BCG-unresponsive HR NMIBC.