Real-world comparative effectiveness of first-line (1L) cabozantinib (C) versus cabozantinib with nivolumab (C+N) in patients (pts) with metastatic papillary renal cell carcinoma (mPRCC).

461 Background: mPRCC is the most common non-clear cell renal cell carcinoma (RCC). Standard of care options include both C and C+N (NCCN Guidelines V1.2026) due to a lack of randomized clinical trial results in this setting and are currently being investigated in SWOG PAPMET2 (NCT05411081). Herein, we aimed to evaluate the comparative effectiveness of C versus C+N in pts with mPRCC using a large, real-world database. Methods: This is an IRB approved retrospective study using the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility: pts with mPRCC who received 1L treatment with C+N or C monotherapy from 4/29/2017 - 7/16/2024. Pts were classified into two groups based on treatment with C+N or C. Endpoints: real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS), summarized via Kaplan-Meier survival estimates and their 95% confidence intervals (CIs) and compared in the context of propensity score (PS) matching weighted analysis with the Cox proportional hazard model. The PS was constructed using logistic regression with the baseline covariates: age, race-ethnicity, gender, region, socioeconomic status, practice type, insurance, smoking status, prior nephrectomy, IMDC risk score, and 1L start year. Results: Of the 13,909 pts in the enhanced cohort, 115 pts with mPRCC were eligible and included (65 pts: C and 50 pts: C+N). The median rwTTNT for C was 6.4 months (mo) (95% CI 5.2-11) vs 11 mo (95% CI 8.4-23) for C+N (hazard ratio HR 0.70, 95% CI 0.45-1.08, p = 0.11). The median rwOS for C was 19 mo (95% CI 13-31) vs 27 mo (14-not reached NR) for C+N (HR 0.92, 95% CI 0.56-1.52, p = 0.8). After PS matching weighting, the median rwTTNT for C was 6.4 mo (95% CI 4.9-14) vs 16 mo (11-NR) for C+N (HR 0.51, 95% CI 0.28-0.92, p = 0.027). After PS matching weighting, the median rwOS for C was 20 mo (95% CI 11-44) vs 26 mo (95% CI 16-NR) for C+N (HR 0.87, 95% CI 0.45-1.69, p = 0.7). Conclusions: In this study of pts with mPRCC following PS matching weighting analysis, 1L C+N was associated with improved rwTTNT as compared to C monotherapy. However, there was no evidence of significant difference in rwOS between both groups. These hypothesis generating data need prospective validation in ongoing PAPMET2 trial. Limitations include lack of randomization, potential selection bias, and residual confounding.