Real-life Use of Cabozantinib in Front-line therapy for Metastatic Renal Cell Carcinoma: The CabFRONT Study (Meet-URO 24).

Background and objective: Cabozantinib remains the cornerstone for treatment of patients metastatic renal cell carcinoma (mRCC), whether pretreated with an immune-oncology (IO) agent and/or tyrosine kinase inhibitor, or treatment-naïve but ineligible for IO-based combinations. Methods: CabFRONT (Meet-URO 24) was a retrospective, observational, multicentre study of a real-life population of treatment-naïve patients with intermediate-risk or poor-risk mRCC treated with cabozantinib. Key findings and limitations: A total of 211 treatment- naïve patients with intermediate- or poor-risk mRCC according to the International Metastatic RCC Database Consortium criteria were included. At median follow-up of 50.4 mo (interquartile range 46.9-53.2), median progression-free survival (PFS) was 9.1 mo (interquartile range 7.4-10.4) and median overall survival (OS) was 19.8 mo (95% confidence interval [CI] 14.1-27.0). A reduced dose was not associated with significant differences in median OS (hazard ratio [HR] 1.08, 95% CI 0.77-1.52; p = 0.7) or PFS (HR 1.25, 95% CI 0.91-1.70; p = 0.16). A modified schedule because of toxicities was also not associated with significant differences in survival or progression (HR for death 0.56, 95% CI 0.25-1.28; p = 0.16; HR for progression or death 0.88, 95% CI 0.48-1.64; p= 0.7). The objective response rate according to Response Evaluation Criteria in Solid Tumours version 1.1 was 39%. The most common grade 3 adverse events were mucositis (9%), fatigue (9%), and diarrhoea (8.5%). Conclusions and clinical implications: Front-line cabozantinib was effective and safe in an unselected real-life population of patients with intermediate-risk or poor-risk mRCC. Cabozantinib could be a choice for patients who cannot receive IO-based combinations or a speculative option for individuals with "early progression" on adjuvant IO. Patient summary: We looked at outcomes for patients with metastatic kidney cancer treated with an inhibitor called cabozantinib in a large European population. We found that cabozantinib is active and safe, and that changes in the dose or treatment schedule because of side effects do not affect outcomes. Cabozantinib could be an option for patients who cannot receive immunotherapy for metastatic disease.