Clinical Effectiveness of Targeted Therapies Following Nivolumab Therapy in Patients with Metastatic Renal Cell Carcinoma: A Real-World Study

Background: The treatment and escape for metastatic renal cell carcinoma (RCC) has rapidly evolved, particularly with the integration of immune therapies into first-line regimens. However, optimal strategies following progression in first-line immunotherapy remain uncertain. This study aims to evaluate the efficacy and safety of axitinib and cabozantinib as third-line therapies after progression on nivolumab following first-line VEGF-TKI therapy. Methods: Patients with metastatic RCC who progressed on prior nivolumab treatment after receiving first-line VEGF-TKI therapy were included. Data on patient characteristics, treatment regimens, response rates, progression-free survival (PFS), and overall survival (OS) were collected. Statistical analyses were conducted to assess the prognostic factors and treatment outcomes. Results: A total of 46 patients were included who were predominantly male (83%) with clear-cell histology (89%). The median PFS on first-line TKI therapy was 10.2 months. All the patients received nivolumab as a second-line therapy, with a median of 12 cycles. The median second-line PFS was seven months. Third-line therapies included axitinib (24 patients) and cabozantinib (20 patients). The median PFS for axitinib and cabozantinib was six months, with comparable survival outcomes. The IMDC risk group and treatment tolerability were significant predictors of survival in multivariate analysis. Adverse events were manageable, with hypertension, fatigue, and diarrhea being the most common. Conclusion: Axitinib and cabozantinib show promise as third-line therapies post-nivolumab progression in metastatic RCC, though prospective validation is warranted. This study underscores the need for further research to establish treatment standards in this evolving landscape.