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.