Correlation of Radiation Pneumonitis History Before Nivolumab with Onset of Interstitial Lung Disease and Progression-free Survival of Patients with Pre-treated Advanced Non-small Cell Lung Cancer

AKIHIRO TAMIYA; MOTOHIRO TAMIYA; KENJI NAKAHAMA; YOSHIHIKO TANIGUCHI; TAKAYUKI SHIROYAMA; SHUN-ICHI ISA; TAKAKO INOUE; KYOICHI OKISHIO; KAZUMI NISHINO; TORU KUMAGAI; HIDEKAZU SUZUKI; TOMONORI HIRASHIMA; FUMIO IMAMURA; SHINJI ATAGI

Abstract

Background/Aim: Nivolumab has a promising efficacy for patients with non-small-cell lung cancer (NSCLC) as second-line or later treatment, and after radiotherapy as abscopal effect. However, the effects of radiation pneumonitis history before nivolumab have not been clarified. Therefore, we retrospectively analyzed the correlation of a history of radiation pneumonitis before nivolumab with onset of interstitial lung disease (ILD) and progression-free survival (PFS) after nivolumab treatment in patients with previously treated NSCLC. Patients and Methods: A total of 201 patients treated with nivolumab were retrospectively reviewed. We collected clinical data of patients at the time of starting nivolumab and we evaluated ILD incidence and PFS in relation to patient characteristics, including radiation pneumonitis history. Results: The median age was 68 years; 135 patients were men, 157 had a smoking history, and 153 had performance status of 0 or 1. Thirty-four patients experienced radiation pneumonitis before nivolumab, and 50 patients received radiotherapy to the chest (31 patients received curative radiotherapy). The overall median PFS was 2.8 months and the overall ILD rate was 12.4%. Higher ILD incidence was observed in the group with a history of radiation pneumonitis (26.5%) compared to the group without radiation pneumonitis (9.6%). The median PFS was 3.6 and 2.3 months, respectively. On multivariate analysis, a history of radiation pneumonitis was also significantly correlated with good PFS (p=0.023). Conclusion: Although increasing the risk of ILD, a history of radiation pneumonitis before nivolumab also contributes to the prolongation of PFS after nivolumab.

Footnotes

Funding
This study was supported by Ono pharmaceutical Co., Ltd and Bristol-Myers Squibb Co., Ltd.
Conflicts of Interest
Dr. Y. Taniguchi, Dr. A. Tamiya, Dr. S. Isa, Dr. K. Nakahama, Dr. T. Shiroyama, Dr. H. Suzuki, Dr. T. Inoue, Dr. M. Tamiya, Dr. T. Hirashima, Dr. F. Imamura, and Dr. S. Atagi report grants from Ono Pharmaceutical and Bristol-Myers Squibb. Dr. Y. Taniguchi, Dr. A. Tamiya, Dr. T. Shiroyama, Dr. H. Suzuki, Dr. M. Tamiya, Dr. T. Hirashima, Dr. F. Imamura, and Dr. S. Atagi report personal fees from Ono Pharmaceutical. Dr. Y. Taniguchi, Dr. A. Tamiya, Dr. M. Tamiya, Dr. T. Hirashima, Dr. F. Imamura, and Dr. S. Atagi report personal fees from Bristol-Myers Squibb during the conduct of the study. Dr. Y. Taniguchi reports personal fees from Chugai Pharmaceutical outside the submitted work. Dr. A. Tamiya reports personal fees from Chugai Pharmaceutical, AstraZeneka, Eli Lilly, and Boehringer Ingelheim outside the submitted work. Dr. K. Okishio reports personal fees from Ono Pharmaceutical outside the submitted work. Dr. T. Shiroyama reports personal fees from Taiho Pharmaceutical, Boehringer Ingelheim, and AstraZeneca outside the submitted work. Dr. H. Suzuki reports personal fees from Taiho Pharmaceutical, Boehringer Ingelheim, Pfizer, and Eli-Lilly outside the submitted work. Dr. M. Tamiya reports personal fees from Chugai Pharmaceutical, Pfizer, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Asahi Kasei Pharmaceutical, Daichi Sankyo CO. LTD. Alere Medical and Boehringer Ingelheim outside the submitted work. Dr. K. Nishino reports personal fees from Chyugai, Boehringer Ingelheim, Eli Lilly, and AstraZeneca outside the submitted work. Dr. T. Kumagai reports personal fees from Ono Pharmaceutical, Astra Zeneca, and Boehringer Ingelheim outside the submitted work. Dr. T. Hirashima reports grants and personal fees from MSD Oncology, Lilly Japan, AstraZeneca, Chugai Pharma, and Boehringer Ingelheim, grants from Eisai, Daiichi Sankyo, Merck Serono, Taiho Pharmaceutical, Kyowa Hakko Kirin, and Takeda, and personal fees from Bayer outside the submitted work. Dr. F. Imamura reports personal fees from Pfizer Inc., AstraZeneca K. K., Novartis Pharma K. K., Kyowa Hakko Kirin Co. Ltd., Boehringer Ingelheim GmbH, Taiho Pharmaceutical Co. Ltd., Eli Lilly Japan K. K., Chugai Pharmaceutical Co. Ltd. outside the submitted work. Dr. S. Atagi reports grants from Pfizer, Chugai Pharmaceutical, AstraZeneca, MSD, Taiho Pharmaceutical, Yakult Pharmaceutical Industry, Eli Lilly, and Boehringer Ingelheim, and personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Eli Lilly, and Boehringer Ingelheim outside the submitted work.
Research Involving Human Participants
Ethical approval: The study protocol was approved by the Institutional Review Board of the three participants' institutions. This study was registered at UMIN; UMIN-ID: UMIN000025908.
Informed Consent
Informed consent was obtained from all individual participants included in the study.