Efficacy and safety of second-line cabozantinib after immuno-oncology combination therapy for advanced renal cell carcinoma: Japanese multicenter retrospective study

Abstract

Immuno-oncology (IO) combination therapy is utilized as a first-line systemic treatment for advanced renal cell carcinoma. However, evidence supporting the use of cabozantinib after IO combination therapy is lacking. We retrospectively analyzed patients who received second-line cabozantinib after IO combination therapy using the Japanese Urological Oncology Group (JUOG) database. In total, 254 patients were enrolled in the JUOG global study, and 118 patients who received second-line cabozantinib comprised the study cohort. The objective response rate, disease control rate, second-line cabozantinib progression-free survival (PFS), and overall survival from second-line for overall were 32%, 75%, 10.5 months, and not reached, respectively, for first-line IO-IO therapy were 37%, 77%, 11.1 months, and not reached, respectively, versus 24%, 71%, 8.3 months, and not reached, respectively, for first-line IO-tyrosine kinase inhibitor therapy. In univariate and multivariate analyses, discontinuation of first-line treatment because of progressive disease and liver metastasis were independent risk factors for PFS. All-grade adverse events occurred in 72% of patients, and grade 3 or higher adverse events occurred in 28% of patients. Second line-cabozantinib after first-line IO combination therapy for advanced renal cell carcinoma was expected to be effective after either IO-IO or IO-TKI treatment and feasible in real-world practice.

Figure 1

Progression-free survival for second-line cabozantinib after first-line immuno-oncology (IO) combination therapy. Rates were estimated using the Kaplan–Meier method. (a) All patients. (b) In patients who received first-line IO-IO therapy. (c) Patients who received first-line IO-tyrosine kinase inhibitor therapy. NE not evaluable.

Figure 2

Overall survival for second-line cabozantinib after first line immuno-oncology (IO) combination therapy. Rates were estimated using the Kaplan–Meier method. (a) All patients. (b) In patients who received first-line IO-IO therapy. (c) Patients who received first-line IO-tyrosine kinase inhibitor therapy. NR not reached, NE not evaluable.

Figure 3

Progression-free survival for second-line cabozantinib after first-line immuno-oncology combination therapy based on independent risk factors. Rates were estimated using the Kaplan–Meier method. (a) Reason for first-line treatment discontinuation. (b) Presence of liver metastasis. AE adverse event, PD progressive disease, HR hazard ratio, CI confidence interval.

Figure 4

Progression-free survival (PFS) and overall survival (OS) for third-line treatment after second-line cabozantinib. Rates were estimated using the Kaplan–Meier method. (a) PFS. (b) OS.