A matched-adjusted indirect comparison (MAIC) of nogapendekin alfa inbakicept-pmln plus bacillus Calmette–Guérin (NAI+BCG) and pembrolizumab in patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) ± papillary disease.

Abstract

e16619 Background: Several FDA approved treatments offer bladder-sparing options for patients with BCG-unresponsive NMIBC CIS ± papillary disease. In the absence of head-to-head trials, indirect treatment comparison (ITC) methodologies can provide robust assessments between approved treatments. An unanchored, matched-adjusted indirect comparison (MAIC) was used to compare the efficacy of nogapendekin alfa inbakicept-pmln + BCG (NAI+BCG) versus pembrolizumab (PEMBRO). Methods: Feasibility assessments between the phase 3 NAI+BCG study (QUILT-3.032; NCT03022825) and a phase 3 PEMBRO study (KEYNOTE-057; NCT0262596) trials confirmed suitability for ITC on efficacy endpoints. Patient-level data from QUILT-3.032 were matched in an MAIC or weighted in a simulated treatment comparison (STC) against aggregate KEYNOTE-057 data. Endpoints included complete response (CR) at 12-months, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Restricted mean survival time analysis was used for time-based treatment effect for PFS and OS. Five mutually reported baseline variables (age ≥65, sex, ECOG status, race, stage) were included to minimize bias. Differences in administration limited modeling treatment-related adverse events (TRAEs). Effective sample size and E-values assessed weighting adequacy and robustness to unmeasured confounding in modeling. Results: The weighted MAIC analysis shows that NAI+BCG achieved higher CR at 12 months compared to PEMBRO (47.3% vs 18.8%; odds ratio [OR] 3.88 [95% CI: 1.77-8.50]). The adjusted STC base case found that NAI+BCG patients had a longer DOR compared to PEMBRO, with a median difference of 10.65 months (26.85 vs 16.20 [95% CI: 3.70-8.42]) with sensitivity analysis demonstrating similar outcomes. At 43-month cutoff, the median PFS favored NAI+BCG (median not reached) compared to 39.9 months for PEMBRO (hazard ratio: 0.45 [95% CI: 0.17, 1.20]). No significant difference was found in OS. Odds of non-bladder related grade 3-4 TRAEs favored NAI+BCG vs PEMBRO (OR: 0.33 [95% CI: 0.00, 4.09]). E-values supported model robustness to unmeasured confounding. Conclusions: In this MAIC, NAI+BCG provided a higher CR rate and longer DOR compared to PEMBRO for BCG-unresponsive NMIBC CIS patients. The results provide novel comparative effectiveness data that may be helpful in shared clinical decision-making. Findings should be interpreted cautiously due to inherent limitations of unanchored MAICs.