AUTHOR=Fujisaki Toshiya , Watanabe Satoshi , Ota Takeshi , Kushiro Kohei , Sato Yusuke , Takahashi Miho , Ohtsubo Aya , Shoji Satoshi , Nozaki Koichiro , Ichikawa Kosuke , Hokari Satoshi , Kondo Rie , Miyabayashi Takao , Abe Tetsuya , Miura Satoru , Tanaka Hiroshi , Okajima Masaaki , Terada Masaki , Matsumoto Naoya , Ishida Takashi , Iwashima Akira , Sato Kazuhiro , Yoshizawa Hirohisa , Aoki Nobumasa , Hayashi Masachika , Ohshima Yasuyoshi , Koya Toshiyuki , Kikuchi Toshiaki TITLE=The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.704475 DOI=10.3389/fonc.2021.704475 ISSN=2234-943X 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.