The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

Toshiya Fujisaki; Satoshi Watanabe; Takeshi Ota; Kohei Kushiro; Yusuke Sato; Miho Takahashi; Aya Ohtsubo; Satoshi Shoji; Koichiro Nozaki; Kosuke Ichikawa; Satoshi Hokari; Rie Kondo; Takao Miyabayashi; Tetsuya Abe; Satoru Miura; Hiroshi Tanaka; Masaaki Okajima; Masaki Terada; Naoya Matsumoto; Takashi Ishida; Akira Iwashima; Kazuhiro Sato; Hirohisa Yoshizawa; Nobumasa Aoki; Masachika Hayashi; Yasuyoshi Ohshima; Toshiyuki Koya; Toshiaki Kikuchi

doi:10.3389/fonc.2021.704475

The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

Front Oncol. 2021 Sep 24:11:704475. doi: 10.3389/fonc.2021.704475. eCollection 2021.

Authors

Toshiya Fujisaki¹, Satoshi Watanabe¹, Takeshi Ota², Kohei Kushiro¹, Yusuke Sato¹, Miho Takahashi¹, Aya Ohtsubo¹, Satoshi Shoji¹, Koichiro Nozaki¹, Kosuke Ichikawa¹, Satoshi Hokari¹, Rie Kondo¹, Takao Miyabayashi³, Tetsuya Abe³, Satoru Miura⁴, Hiroshi Tanaka⁴, Masaaki Okajima⁵, Masaki Terada⁵, Naoya Matsumoto⁶, Takashi Ishida⁷, Akira Iwashima⁸, Kazuhiro Sato⁹, Hirohisa Yoshizawa¹⁰, Nobumasa Aoki¹, Masachika Hayashi¹, Yasuyoshi Ohshima¹, Toshiyuki Koya¹, Toshiaki Kikuchi¹

Affiliations

¹ Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
² Department of Respiratory Medicine, Niigata Prefectural Shibata Hospital, Niigata, Japan.
³ Department of Respiratory Medicine and Infectious Diseases, Niigata City General Hospital, Niigata, Japan.
⁴ Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
⁵ Department of Respiratory Medicine, Saiseikai Niigata Hospital, Niigata, Japan.
⁶ Department of Respiratory Medicine, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
⁷ Department of Respiratory Medicine, Niigata Prefectural Central Hospital, Joetsu, Japan.
⁸ Department of Respiratory Medicine, Nagaoka Chuo General Hospital, Nagaoka, Japan.
⁹ Department of Respiratory Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan.
¹⁰ Department of Respiratory Medicine, Niigata Medical Center, Niigata, Japan.

Abstract

Objectives: Although immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs.

Methods: We retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors.

Results: Of 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4-NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4-NE); p = 0.031].

Conclusion: The current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

Keywords: NSCLC; PD-1; drug therapy; immune-related adverse event; immunology.

Copyright © 2021 Fujisaki, Watanabe, Ota, Kushiro, Sato, Takahashi, Ohtsubo, Shoji, Nozaki, Ichikawa, Hokari, Kondo, Miyabayashi, Abe, Miura, Tanaka, Okajima, Terada, Matsumoto, Ishida, Iwashima, Sato, Yoshizawa, Aoki, Hayashi, Ohshima, Koya and Kikuchi.