Real-world comparison of cabozantinib and sunitinib in advanced non-clear cell renal cell carcinoma: A multicenter study by the Turkish Oncology Group.

Non-clear cell renal cell carcinoma (nccRCC) comprises a heterogeneous group of malignancies with limited prospective data and no established first-line standard. We conducted a multicenter retrospective study across 29 centers in Turkey, including patients with advanced or metastatic nccRCC treated with first-line cabozantinib or sunitinib between 2015 and 2025. Among 268 patients (sunitinib, n = 198; cabozantinib, n = 70), baseline characteristics were balanced. Cabozantinib was associated with significantly longer median progression-free survival (PFS) compared to sunitinib (9.2 vs. 6.6 months; HR: 0.66; p = .027), while overall survival (OS) was similar (18.6 vs. 17.2 months; p = .566). Objective response rate (ORR) was higher with cabozantinib (38.6% vs. 26.3%; p = .052). Multivariate analyses identified ECOG performance status ≥2, IMDC risk category, sarcomatoid differentiation, and chromophobe histology as independent prognostic factors for OS. Predictors of PFS included IMDC risk, sarcomatoid features, nephrectomy status, and histologic subtype. These findings suggest that cabozantinib may offer improved disease control over sunitinib in this diverse patient population and provide valuable real-world insights for therapeutic decision-making in the absence of prospective randomized data.