1202 - Radiographic characteristics and poor prognostic factors of interstitial lung disease (ILD) in nivolumab-treated patients with non-small cell lung cancer (NSCLC)

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.

Clinical trial identification

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): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Shionogi; Honoraria (self): Eisai; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self): MSD; Honoraria (self): Taiho; Honoraria (self), Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): Kyorin; Honoraria (self): Tsumura. All other authors have declared no conflicts of interest.