Pneumonitis During Durvalumab Consolidation Therapy Affects Survival in Stage III NSCLC

Yuhei Kinehara; Takayuki Shiroyama; Akihiro Tamiya; Motohiro Tamiya; Seigo Minami; Masaki Kanazu; Osamu Morimura; Toshie Niki; Satoshi Tetsumoto; Yoshihiko Taniguchi; Tomoki Kuge; Kazumi Nishino; Izumi Nagatomo; Atsushi Kumanogoh; Isao Tachibana

doi:10.1016/j.jtocrr.2023.100586

Pneumonitis During Durvalumab Consolidation Therapy Affects Survival in Stage III NSCLC

JTO Clin Res Rep. 2023 Oct 12;4(11):100586. doi: 10.1016/j.jtocrr.2023.100586. eCollection 2023 Nov.

Authors

Yuhei Kinehara¹, Takayuki Shiroyama², Akihiro Tamiya³, Motohiro Tamiya⁴, Seigo Minami⁵, Masaki Kanazu⁶, Osamu Morimura⁷, Toshie Niki⁸, Satoshi Tetsumoto⁹, Yoshihiko Taniguchi³, Tomoki Kuge^{2

6}, Kazumi Nishino⁴, Izumi Nagatomo², Atsushi Kumanogoh^{2

10

11

12

13

14}, Isao Tachibana¹

Affiliations

¹ Department of Respiratory Medicine and Clinical Immunology, Nippon Life Hospital, Osaka, Japan.
² Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
³ Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan.
⁴ Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁵ Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan.
⁶ Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, Osaka, Japan.
⁷ Department of Respiratory Medicine, Toyonaka Municipal Hospital, Osaka, Japan.
⁸ Department of Respiratory Medicine, Nishinomiya Municipal Central Hospital, Hyogo, Japan.
⁹ Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital, Osaka, Japan.
¹⁰ Department of Immunopathology, WPI, Immunology Frontier Research Center (iFReC), Osaka University, Osaka, Japan.
¹¹ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
¹² Center for Infectious Diseases for Education and Research (CiDER), Osaka University, Suita, Osaka, Japan.
¹³ Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Osaka University, Osaka, Japan.
¹⁴ Center for Advanced Modalities and DDS (CAMaD), Osaka University, Osaka, Japan.

Abstract

Introduction: Durvalumab consolidation therapy is the standard of care after concurrent chemoradiotherapy (CRT) for stage III NSCLC. Immune-related pneumonitis during durvalumab treatment is potentially fatal; however, information is lacking regarding the impact of pneumonitis on patient survival. This study investigates the effect of pulmonary and nonpulmonary immune-related adverse events (irAEs) on the efficacy of durvalumab treatment in patients with stage III NSCLC.

Methods: We retrospectively assessed 158 patients who received durvalumab after CRT at nine Japanese institutions between July 2018 and March 2020. Survival outcomes were compared between patients who developed pneumonitis with those who developed irAEs other than pneumonitis. Patients who survived for less than 3 months were excluded to reduce immortal time bias.

Results: Among 158 evaluated patients, 76 (48%) experienced grade less than or equal to one irAEs, whereas 82 (52%) experienced grade greater than or equal to two irAEs. Among the patients with grade greater than or equal to two irAEs, those with grade greater than or equal to two pneumonitis (n = 55) were compared with those with grade greater than or equal to two irAEs other than pneumonitis (n = 27). Patients with grade greater than or equal to two pneumonitis exhibited a significantly worse overall survival than those with grade greater than or equal to two irAEs that excluded pneumonitis. Multivariate analysis revealed that grade greater than or equal to two pneumonitis (hazard ratio = 3.71; 95% confidence interval, 1.85-7.45; p < 0.001) and squamous histology (hazard ratio = 2.64; 95% confidence interval, 1.29-5.42; p = 0.008) were independently associated with worse overall survival.

Conclusions: After minimizing immortal time bias, pneumonitis grade two or greater and squamous histology were poor prognostic factors in patients who received consolidation durvalumab after CRT.

Keywords: Chemoradiotherapy; Durvalumab; Immune-related adverse event; Pneumonitis; Stage III.