Metastatic renal cell carcinoma treated with pembrolizumab–lenvatinib versus nivolumab–cabozantinib: A real-world analysis.

e16519 Background: Pembrolizumab plus lenvatinib (P-L) and nivolumab plus cabozantinib (N-C) are approved first-line options for patients with metastatic renal cell carcinoma (RCC). While each regimen has demonstrated efficacy in clinical trials, direct comparisons of their real-world outcomes remain limited. Methods: We conducted a retrospective, multi-institutional cohort study across 60 healthcare organizations using the TriNetX network, including patients with metastatic RCC diagnosed after January 2021 who received first-line P-L or N-C within 6 months of diagnosis. To minimize confounding, 1:1 propensity score matching was performed based on demographics, comorbidities, body mass index, laboratory parameters (hemoglobin, LDH, and albumin), the presence of visceral, bone, and brain metastases, and prior systemic corticosteroid exposure. Outcomes included all-cause mortality, emergency department (ED) visits, inpatient hospitalization, intensive care unit (ICU) admission, immune-related adverse events (dermatologic, endocrine, gastrointestinal, hepatic, and pulmonary), and systemic corticosteroid use. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Results: A total of 752 patients were identified, including 504 in the N–C group and 248 in the P–L group. After 1:1 propensity score matching, 238 patients were included in each cohort. The mean age at treatment initiation was 62 years, and 72% of patients were male. Median follow-up was 14 months in the N–C group and 16 months in the P–L group. Median overall survival was not reached in either cohort as mortality remained below 50%, though survival outcomes were comparable (HR 0.97; 95% CI, 0.72–1.30; p = 0.852). All-cause mortality was comparable between groups at 1 year (RR 1.07; 95% CI, 0.78–1.47; p = 0.669) and 2 years (RR 1.02; 95% CI, 0.80–1.32). ED visits, inpatient hospitalizations, and ICU admissions were similar between groups within 1 year and 2 years. The most common immune-related adverse events were endocrine, dermatologic, and gastrointestinal, with no significant differences between groups in dermatologic (RR 0.96; 95% CI, 0.74–1.25), endocrine (RR 1.12; 95% CI, 0.94–1.33), gastrointestinal (RR 1.02; 95% CI, 0.71–1.46), or systemic corticosteroid use (RR 1.01; 95% CI, 0.92–1.11). Conclusions: In this real-world cohort of first-line therapy, P–L and N–C were associated with similar overall survival and comparable 1- and 2-year all-cause mortality, healthcare utilization, and immune-related adverse events. With comparable survival outcomes in this matched analysis, treatment selection between P–L and N–C may be guided by patient-specific factors, toxicity profiles, and cost considerations rather than anticipated differences in efficacy, though these findings should be interpreted in the context of this retrospective, real-world analysis.