Clinical resistance predictors to first-line VEGFR-TKI monotherapy for metastatic renal cell carcinoma: a retrospective multicenter real-life case series

Aim: For many years, systemic treatment of metastatic Renal Cell Carcinoma (mRCC) was based on sequential targeted agent monotherapies. In this real-life case series, we evaluated easily accessible clinical factors useful for disease course prediction. Methods: We exploited patients' clinical pathological characteristics and systemic treatment outcomes in a real world population of 365 mRCC patients who received sequential monotherapies in the targeted therapy era, and we identified an early progressors subpopulation, resistant to first-line VEGFR-TKI monotherapy in less than 6 months. Results: Early progressors (n = 124) show a far worse OS compared with patients progressing beyond the sixth month of therapy (13.5 vs. 44.8 months, P -value < 0.0001, HR = 0.41, 95%CI: 0.29-0.53). However, these patients did not show far worse performance in second and third-line settings compared to first-line responders. In the univariate analysis, IMDC risk class, sarcomatoid features, and Systemic Inflammation Index (SII) were correlated with first-line therapy Progression-Free Survival (PFS1). In multivariate analysis, variables correlated with first-line outcome were IMDC risk class, histotype, and number of metastatic sites at the diagnosis. Conclusion: Real-world data can contribute to developing easy-to-use prognostic factors associated with refractory disease that could support clinicians in identifying the most appropriate treatment strategy for each patient.