Abstract Code: IUC24419-85

Real-life experience with metastatic renal cell carcinoma treated with combination of Cabozantinib and Nivolumab: A single-center retrospective analysis

L. Stumbo 1, C. Mone 1, G. Tonini 1

(1) Fondazione Policlinico Univeristario Campus Bio-Medico, Rome – Italy

Background

Metastatic renal cell carcinoma (mRCC) remains a challenging entity characterized by marked clinical and biological heterogeneity. This retrospective study reports the real-world experience of a single oncology center in Italy with first-line treatment using the combination of cabozantinib and nivolumab.

Methods

We conducted a retrospective analysis of data from seven consecutive patients diagnosed with mRCC between 2023 and 2025. The primary objective was to evaluate treatment outcomes and tolerability in a real-life setting.

Results

Median age at diagnosis was 59 years. All patients presented with stage IV disease at baseline. Clear-cell renal cell carcinoma represented the most frequent histology. Predominant metastatic sites were lungs and lymph nodes, followed by liver, bone, brain, and peritoneum. Two patients underwent cytoreductive nephrectomy, and two received radiotherapy as part of a multimodal approach. All patients received first-line treatment with cabozantinib (40 mg/day in 6 patients; 20 mg/day in one patient due to poor PS) combined with nivolumab (240 mg every 2 weeks). Sunitinib was used as a second-line option in selected cases. The most common treatment-related adverse event was diarrhea of grade <3, which occurred in multiple patients and was pharmacologically manageable. Notably, three patients required temporary discontinuation of therapy due to grade 2 diarrhea. One patient experienced a massive pulmonary thromboembolism,

and another suspended treatment due to grade 2 hepatotoxicity. Despite these events, only one patient required a dose reduction of cabozantinib to 20 mg/day. No grade 4 or life-threatening toxicities were reported. At the time of data analysis, five patients were alive. The two died patients exhibited a median progression-free survival (PFS) of 6.5 months. Overall survival (OS) could not be estimated due to the limited follow-up and small cohort size.

Conclusions

Our early real-world experience supports the clinical efficacy and manageable safety profile of cabozantinib plus nivolumab as a first-line treatment in mRCC. Although temporary treatment interruptions occurred in response to specific adverse events, dose reduction was infrequent. High metastatic burden and the presence of brain metastases appeared to correlate with worse prognosis. Further studies with larger cohorts and longer follow-up are needed to optimize individualized treatment strategies for mRCC.