Real-World effectiveness of second-line cabozantinib in metastatic renal cell carcinoma in the era of immunotherapy combinations: Results from the international metastatic renal cell carcinoma database consortium (IMDC)

Background Cabozantinib is approved as a subsequent therapy for patients with metastatic renal cell carcinoma (mRCC) based on the METEOR trial. However, only 5% of patients in this trial received prior immunotherapy. Objective Analyze the effectiveness of Cabozantinib in the second-line setting after different first-line treatments. Methods This retrospective study analyzed patients with mRCC who received second-line Cabozantinib between 2010 and 2023, using the International mRCC Database Consortium (IMDC). Patients were grouped by prior therapy and IMDC risk category. We assessed overall response rate (ORR), time to next treatment (TTNT), treatment duration (TD), and overall survival (OS). Results Among 603 patients (mean age 59 years), 31.5% had received IO-IO regimens, 24.5% IO-TKI combinations, and 34.3% TKI monotherapy as initial therapy. At Cabozantinib start, 13.8% were favorable-risk, 49.1% intermediate-risk, and 16.7% poor-risk per IMDC. The ORR for the overall cohort was 25.7%; median TTNT was 10.1 months; median TD was 8.9 months; and median OS was 19.0 months. Efficacy outcomes were consistent across first-line treatment groups. Conclusion This real-world analysis supports the effectiveness of Cabozantinib in the second-line setting, including among patients previously treated with immune checkpoint inhibitors. Prior treatment type did not significantly affect Cabozantinib outcomes.