Cabozantinib After Immunotherapy in Advanced Renal Cell Carcinoma. The CARE Study by the Hellenic Gu Cancer Group

Abstract

Background The widespread use of immune checkpoint inhibitor (ICI)–based combinations as first-line therapy for metastatic renal cell carcinoma (mRCC) has created an unmet need for effective treatment options at disease progression. Cabozantinib is recommended after ICI failure; however, real-world evidence regarding its efficacy and safety in this setting remains limited, particularly following contemporary ICI-containing regimens. Methods CARE was a retrospective, multicenter, non-interventional study conducted in Greece. Patients with locally advanced or metastatic RCC who received cabozantinib monotherapy after progression on at least one prior ICI-containing regimen were included. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses evaluated outcomes according to prior therapies and timing of cabozantinib administration. Results Thirty patients were included. Prior immunotherapy consisted mainly of nivolumab monotherapy or nivolumab plus ipilimumab, while cabozantinib was administered predominantly as second-line treatment. No complete responses were observed; twelve patients achieved partial response, resulting in an ORR of 40% (95% CI: 22.7–59.4). Stable disease was observed in 56.7% of patients. Median follow-up was 20 months (95% CI 15.2–24.6). Median PFS was 21 months (95% CI: 12.5–NR), and median OS was 29.7 months (95% CI: 25.5–NR). Prior exposure to tyrosine kinase inhibitors was associated with shorter PFS, while ORR and OS were not significantly affected. Cabozantinib demonstrated a manageable safety profile, with fatigue and diarrhea being the most common adverse events. Grade III–IV toxicities occurred in 26.7% of patients. Conclusion In this real-world Greek cohort, cabozantinib demonstrated meaningful clinical activity and an acceptable safety profile in mRCC patients progressing after ICI-based therapy. These findings support cabozantinib as an effective treatment option in the post-immunotherapy setting and contribute valuable real-world evidence to inform therapeutic sequencing in mRCC.