Real‐World Outcomes and Prognostic Factors of Immune Checkpoint Inhibitor Rechallenge for Metastatic Renal Cell Carcinoma: A Multicenter Study

OBJECTIVES: Combination therapies incorporating immune checkpoint inhibitors (ICIs) are widely used as first-line treatment for metastatic renal cell carcinoma (mRCC). However, the optimal sequence of subsequent therapies remains unclear. In this study, we investigated the real-world outcomes of nivolumab rechallenge after first-line ICI-based combination therapy. METHODS: Twenty-eight consecutive patients with mRCC who received nivolumab monotherapy as third- or later-line treatment after first-line ICI-based combination therapy were identified from a multicenter database. The best overall response (BOR), progression-free survival (PFS), overall survival (OS), immune-related adverse events (irAEs), and prognostic factors associated with PFS were retrospectively analyzed. RESULTS: The median age was 68 years. Twenty-two patients (78.6%) had clear cell RCC. Nivolumab was administered as third-, fourth-, and fifth-line therapy in 19 (67.9%), 7 (25.0%), and 2 (7.1%) patients, respectively. The median follow-up period was 6.4 months. The BORs were complete response, partial response, stable disease, and progressive disease in 0, 2 (7.1%), 7 (25.0%), and 19 (67.9%) patients, respectively. The median PFS and OS were 2.2 and 8.8 months, respectively. irAEs occurred in 7 patients (25.0%), including 5 patients (17.9%) with grade 3 irAEs. No grade 4 or higher events were observed. In multivariable analysis, good performance status and a shorter duration of first-line ICI-based combination therapy were associated with improved PFS. CONCLUSIONS: Nivolumab rechallenge demonstrated modest efficacy in patients with mRCC after first-line ICI-based combination therapy, although a limited subset of patients may derive clinical benefit from this approach. irAEs during nivolumab rechallenge were generally manageable.