Comparison of Cabozantinib and Axitinib as Second-line Therapy After Nivolumab Plus Ipilimumab in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Comparative Analysis of Retrospective Real-world Data

Background To date, no studies have compared the treatment outcomes of second-line therapies in patients with metastatic clear cell renal cell carcinoma (ccRCC). This study retrospectively evaluated the efficacy of cabozantinib and axitinib as second-line treatments in patients with metastatic ccRCC who previously received immune-oncology combination therapy. Patients and Methods Patients with metastatic ccRCC treated with cabozantinib and axitinib as second-line therapy after nivolumab-ipilimumab treatment were identified among 243 patients with RCC treated between August 1, 2018 and January 31, 2022 at 34 institutions belonging to the Japanese Urological Oncology Group. Patients were assessed for treatment outcomes, including progression-free survival (PFS), overall survival, objective response rate (ORR), and incidence rate of treatment-related adverse events (AEs). Results Forty-eight patients treated with cabozantinib and 60 treated with axitinib as second-line therapy after nivolumab-ipilimumab treatment for metastatic ccRCC were identified. The median PFS (95% confidence interval) was 11.0 months (9.0–16.0) with cabozantinib and 9.5 months (6.0–13.0) with axitinib. The ORRs were 37.5% (cabozantinib) and 38.3% (axitinib). The rates of any-grade AEs and grade ≥3 AEs were 79.2% (cabozantinib) versus 63.3% (axitinib; P=0.091) and 35.4% (cabozantinib) versus 23.3% (axitinib; P=0.202), respectively. In the poor-risk group, PFS was longer in the cabozantinib group than in the axitinib group (P=0.033). Conclusion The efficacy and safety of cabozantinib and axitinib were comparable. In the poor-risk group, cabozantinib was more effective than axitinib. These findings provide valuable insights into the selection of second-line treatment options after nivolumab-ipilimumab treatment in patients with metastatic ccRCC. MicroAbstract The treatment outcomes of the second-line therapies, cabozantinib and axitinib, following nivolumab and ipilimumab in 108 patients with metastatic clear cell renal cell carcinoma (ccRCC) were retrospectively compared. Comparable efficacy and safety were observed. In the poor-risk group, cabozantinib demonstrated superior progression-free survival over axitinib, offering valuable insights for second-line therapy selection after nivolumab-ipilimumab in patients with metastatic ccRCC.