Takashi Ikeda1, Hiroki Ishihara2, Yuki Nemoto3, Hidekazu Tachibana4, Hironori Fukuda5, Kazuhiko Yoshida5, Toshio Takagi5, Junpei Iizuka5, Yasunobu Hashimoto3, Hideki Ishida5, Tsunenori Kondo4, Kazunari Tanabe5. 1. Department of Urology, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan; Department of Urology, Saiseikai Kawaguchi General Hospital, 5-11-5 Nishikawaguchi, Kawaguchi City, Saitama 332-8558, Japan. 2. Department of Urology, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Electronic address: ishihara.hiroki@twmu.ac.jp. 3. Department of Urology, Saiseikai Kawaguchi General Hospital, 5-11-5 Nishikawaguchi, Kawaguchi City, Saitama 332-8558, Japan. 4. Department of Urology, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan. 5. Department of Urology, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Abstract
OBJECTIVES: Evidence regarding the prognostic impact of immune-related adverse events (irAEs) remains limited in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as a first-line systemic therapy. Thus, we investigated the association between irAE development and oncological outcomes during nivolumab plus ipilimumab therapy. METHODS: We retrospectively evaluated 46 patients with mRCC who were treated with nivolumab plus ipilimumab at our hospital and its affiliated institutions. The associations between irAE development and progression-free survival (PFS), overall survival (OS), and objective response rates (ORRs) were assessed after treatment initiation. RESULTS: A total of 60 irAEs occurred in 33 patients (72%), with 24 grade ≥ 3 irAEs developed in 20 patients (43%). PFS was significantly longer in patients with irAEs than that in patients without irAEs (P < 0.0001); however, OS was not different (P = 0.571). Multivariable analysis further revealed that the development of irAEs was an independent predictor of a longer PFS (hazard ratio: 0.18, P = 0.0005). A landmark analysis for the initial four cycles of nivolumab plus ipilimumab administration also showed that PFS was significantly longer in patients with irAEs than that in patients without irAEs (P = 0.0386). The ORRs were also higher in patients with irAEs (P = 0.0064). Furthermore, in 22 patients (48%) who discontinued nivolumab plus ipilimumab treatment, the 6-month PFS rate was 87%. CONCLUSION: This multi-institutional study showed that irAE development was significantly associated with PFS but not with OS in patients treated with nivolumab plus ipilimumab as a first-line therapy. The development of irAEs may be used as a surrogate prognostic marker for PFS in this treatment regimen.
OBJECTIVES: Evidence regarding the prognostic impact of immune-related adverse events (irAEs) remains limited in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as a first-line systemic therapy. Thus, we investigated the association between irAE development and oncological outcomes during nivolumab plus ipilimumab therapy. METHODS: We retrospectively evaluated 46 patients with mRCC who were treated with nivolumab plus ipilimumab at our hospital and its affiliated institutions. The associations between irAE development and progression-free survival (PFS), overall survival (OS), and objective response rates (ORRs) were assessed after treatment initiation. RESULTS: A total of 60 irAEs occurred in 33 patients (72%), with 24 grade ≥ 3 irAEs developed in 20 patients (43%). PFS was significantly longer in patients with irAEs than that in patients without irAEs (P < 0.0001); however, OS was not different (P = 0.571). Multivariable analysis further revealed that the development of irAEs was an independent predictor of a longer PFS (hazard ratio: 0.18, P = 0.0005). A landmark analysis for the initial four cycles of nivolumab plus ipilimumab administration also showed that PFS was significantly longer in patients with irAEs than that in patients without irAEs (P = 0.0386). The ORRs were also higher in patients with irAEs (P = 0.0064). Furthermore, in 22 patients (48%) who discontinued nivolumab plus ipilimumab treatment, the 6-month PFS rate was 87%. CONCLUSION: This multi-institutional study showed that irAE development was significantly associated with PFS but not with OS in patients treated with nivolumab plus ipilimumab as a first-line therapy. The development of irAEs may be used as a surrogate prognostic marker for PFS in this treatment regimen.