1299PRadiographic characteristics and poor prognostic factors of interstitial lung disease (ILD) in nivolumab-treated patients with non-small cell lung cancer (NSCLC)

• Published in: Annals of oncology Vol. 30; no. Supplement_5
• Main Authors: Sasaki, S, Oikado, K, Saito, Y, Tominaga, J, Sata, M, Sakai, F, Kato, T, Iwasawa, T, Kenmotsu, H, Kusumoto, M, Baba, T, Endo, M, Fujiwara, Y, Sugiura, H, Yanagawa, N, Ito, Y, Sakamoto, T, Ohe, Y, Kuwano, K
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.10.2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz253.124

Abstract Background Nivolumab can cause immune-related adverse events requiring caution, including ILD. Methods Clinical and chest imaging findings for each ILD case reported by nivolumab-treated patients with NSCLC were assessed by the ILD Expert Central Review Committee. ILD prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral infiltration (PTI), a characteristic of nivolumab-induced ILD. Poor prognostic factors were identified by multivariate Cox regression analysis. Results Of patients reported by physicians from December 2015 to March 2016, 325 nivolumab-treated patients with NSCLC assessed for ILD, 238 patients had nivolumab-induced ILD. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (127/238 patients, 53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (48/238 patients, 20.2%), diffuse alveolar damage (DAD) (26/238 patients, 10.9%), and nonspecific interstitial pneumonia-like (fibrosing organizing pneumonia) (15/238 patients, 6.3%). The ILD mortality rate was 65.4% in patients with DAD pattern and 4.2% to 13.6% in patients with the other patterns. The ILD mortality rate was 11.1% in the 27 patients with PTI and 16.3% in the 209 patients without PTI. The antitumor response was as follows: partial response: 34.0%; stable disease: 33.6%; and progressive disease: 21.4% patients. In 5 of the 37 patients who died due to ILD, the radiographic pattern changed to DAD pattern from other patterns at onset. Multivariate Cox regression analysis identified 5 factors for poor prognosis of ILD: DAD pattern; ≤60 days from start of nivolumab treatment to onset of ILD; pleural effusion present before treatment; abnormal opacities distributed contralateral or bilateral to the tumor; and abnormal change in C-reactive protein level. Conclusions Patients with NSCLC with these factors for poor prognosis of nivolumab-induced ILD should be monitored for ILD during nivolumab treatment. Editorial acknowledgement Medical writing assistance was provided by Justine Southby, PhD, CMPP, and Hiroko Ebina, BPharm, Ph, MBA, of ProScribe – Envision Pharma Group, and was funded by Ono Pharmaceutical Co., Ltd. Legal entity responsible for the study Ono Pharmaceutical Co., Ltd. Funding Ono Pharmaceutical Co., Ltd., Osaka, Japan, and Bristol-Myers Squibb K.K., Tokyo, Japan. Disclosure K. Oikado: Honoraria (self): Ono Pharmaceutical ; Honoraria (self): AstraZeneca. Y. Saito: Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Boehringer Ingelheim Co., Ltd.; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): AstraZeneca K.K.; Honoraria (self): Chugai Pharma Co., Ltd.; Honoraria (self): MSD K.K. J. Tominaga: Honoraria (self): Ono Pharmaceutical . M. Sata: Honoraria (self): Ono Pharmaceutical Company. F. Sakai: Honoraria (self): Ono Pharmaceutical ; Honoraria (self): AstraZeneca Co., Ltd.; Honoraria (self): Boehringer Ingelheim Co., Ltd.; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Serono Co., Ltd; Research grant / Funding (institution): Bayer Co., Ltd.; Research grant / Funding (institution): Eisai Co., Ltd.; Honoraria (self): Shionogi Pharmaceuticals Co., Ltd.; Research grant / Funding (institution): Fuji Pharmaceuticals Co., Ltd.; Honoraria (self), Research grant / Funding (institution): Daiichi Pharmaceuticals; Research grant / Funding (institution), Non-remunerated activity/ies: Toshiba; Honoraria (self), Research grant / Funding (institution): Japanese Ministry of Labour, Health and Welfare; Honoraria (self), Research grant / Funding (institution): Japanese Government of Environment. T. Kato: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Honoraria (self), Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self), Research grant / Funding (institution): Kyowa Kirin; Honoraria (self), Research grant / Funding (institution): Merck Sharp and Dohme; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self): F. Hoffmann-La Roche; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Sumitomo Dainippon; Research grant / Funding (institution): Kyorin; Honoraria (self): Nitto Denko; Research grant / Funding (institution): Regeneron; Honoraria (self): Takeda. T. Iwasawa: Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Shionogi & Co., Ltd.; Honoraria (self): Nihon Medi-Physics Co., Ltd.; Honoraria (self): AstraZeneca K.K.; Honoraria (self): Boehringer Ingelheim Japan, Inc.; Honoraria (self): Bayer; Honoraria (self): GE Healthcare Japan; Research grant / Funding (institution): Tsuchiya Foundation ; Research grant / Funding (institution): KAKENHI; Honoraria (self): Canon Medical Systems; Honoraria (self): FujiFilm Medical Systems. H. Kenmotsu: Honoraria (self): Ono Pharmaceutical Co., Ltd; Honoraria (self): Bristol-Myers Squibb K.K.; Honoraria (self), Research grant / Funding (institution): AstraZeneca K.K.; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Chugai Pharmacsutical Co, Ltd.; Honoraria (self): Eli Lilly K.K.; Honoraria (self): Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): MSD K.K.; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Taiho Pharmaceutical Co, Ltd. M. Kusumoto: Advisory / Consultancy, Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd.; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca K.K.; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD K.K.; Research grant / Funding (institution): Canon Medical Systems Corporation. T. Baba: Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Bristol-Myers Squibb K.K.; Honoraria (self): AstraZeneca K.K.; Honoraria (self): Boston Scientific Japan Co., Ltd.; Honoraria (self): Nippon Boehringer Ingelheim Co., Ltd.; Honoraria (self): Daiichi Sankyo Co., Ltd.; Honoraria (self): Toray Industries, INC.; Honoraria (self): Shionogi & Co., Ltd.; Honoraria (self): Astellas Pharma Inc.; Honoraria (self): AMCO Inc; Honoraria (self): Asahi Kasei Pharma Corporation; Travel / Accommodation / Expenses: Kyorin Pharmaceutical Co., Ltd.; Honoraria (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self): MSD K.K. M. Endo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Ono Pharmaceutical. Y. Fujiwara: Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: Sysmex; Speaker Bureau / Expert testimony: Taiho. H. Sugiura: Advisory / Consultancy: Ono Pharmaceutical Co., Ltd.; Advisory / Consultancy: MSD K.K. N. Yanagawa: Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Miss Piggy Products; Advisory / Consultancy, Research grant / Funding (institution): Croak, Inc.; Research grant / Funding (institution), Non-remunerated activity/ies: Sunlight Stop. Inc. Y. Ito: Full / Part-time employment, Employee of the sponsor company: Ono Pharmaceutical Co., LTD. T. Sakamoto: Full / Part-time employment, Employee of the sponsor company: Ono Pharmaceutical Co., LTD. Y. Ohe: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ono; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Advisory / Consultancy: Celltrion; Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Dainippon-Sumitomo; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Kissei; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Janssen. K. Kuwano: Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self), Research grant / Funding (institution): Boehringer; Honoraria (self), Research grant / Funding (institution): Glaxo; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self): AstraZenec