Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

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.

• Authors: Takashi Ikeda, Hiroki Ishihara, Yuki Nemoto, Hidekazu Tachibana, Hironori Fukuda, Kazuhiko Yoshida, Toshio Takagi, Junpei Iizuka, Yasunobu Hashimoto, Hideki Ishida, Tsunenori Kondo, Kazunari Tanabe
• Journal: Urologic oncology (Urol Oncol) Vol. 39 Issue 10 Pg. 735.e9-735.e16 (10 2021) ISSN: 1873-2496 [Electronic] United States
• PMID: 34172370 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Ipilimumab
• Nivolumab

Topics

• Aged
• Carcinoma, Renal Cell (complications, drug therapy, pathology)
• Drug-Related Side Effects and Adverse Reactions (complications)
• Female
• Humans
• Ipilimumab (adverse effects)
• Kidney Neoplasms (complications, drug therapy, pathology)
• Male
• Nivolumab (adverse effects)
• Prognosis
• Retrospective Studies
• Treatment Outcome