Nivolumab (Nivo) demonstrated the promising efficacy for patients (pts) with non-small cell lung cancer (NSCLC) as second or later line treatment. And, abscopal effect of the immune checkpoint inhibitor after the radiotherapy (RT) attracts attention. However, it has not clarified the correlation of radiation pneumonitis history (RPH) before Nivo and onset risk of interstitial lung disease (ILD) or progression free survival (PFS) of Nivo. So we retrospectively analyzed the correlation of RPH before Nivo and onset risk of ILD or PFS of Nivo treatments in patients with NSCLC.
201 pts treated with Nivo from December 2015 to July 2016 were retrospectively reviewed. This study was multicenter study conducted by the three respiratory medical centers in Japan. We collected clinical data including age, sex, smoking history, histological types, performance status (PS), RPH, and history of RT to chest field, at the time of starting Nivo. And we evaluate the ILD and efficacy. We investigated relationship between RPH and ILD or PFS. The data cut off was on the end of November 2016.
Median age was 68 years old, 135 pts were male, 157 pts had smoking history, 153 pts were PS 0 or 1, 34 pts experienced radiation pneumonitis before Nivo, and 50 pts received the RT to chest field (31 pts were curative RT). For all participants, median PFS was 2.8 months (M), overall ILD rate was 12.4%. In the incidence of ILD, no RPH vs RPH; 9.6% vs 26.5% (relative risk ratio (RRR): 2.76, 95% confidence interval (CI): 1.33-5.73), non-RT to chest field vs RT to chest field; 8.6% vs 22.0% (RRR: 2.37, 95% CI: 1.15-4.88). Furthermore, median PFS was no RPH vs RPH; 2.3 M vs 3.6 M, non-RT to chest field vs RT to chest field; 2.2 M vs 3.3 M, and in univariate analysis, RPH had a trend with PFS (hazard ratio (HR): 0.71, 95% CI: 0.44-1.10), however RT to chest field did not correlate with PFS (HR: 1.02, 95% CI: 0.69-1.47). In multivariate analysis, RPH significantly correlated with PFS (HR: 0.58, 95% CI: 0.35-0.93).
The RPH before Nivo not only gives onset risk of ILD but also contributes to the prolongation of PFS of Nivo.
Clinical trial identification
Protoco; number: UMIN000025908 release date: 31th January, 2017
Legal entity responsible for the study
Ono pharmaceutical Co., Ltd and Bristol-Myers Squibb Co., Ltd.
A. Tamiya: Grants from Ono Pharmaceutical, Bristol-Myers Squibb, and received the personal fees from Eli Lilly, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb. M. Tamiya: Grants from Ono Pharmaceutical and Bristol-Myers Squibb, and personal fees from Boehringer Ingelheim, Chugai Pharmaceutical, Pfizer, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Asahi Kasei Pharmaceutical, Daichi Sankyo CO. LTD. Area Medical. K. Nakahama: Grants from Ono Pharmaceutical and Bristol-Myers Squibb. Y. Taniguchi: Grants from Ono Pharmaceutical, grants from Bristol-Myers Squibb, and personal fees from Chugai Pharmaceutical. T. Shiroyama: Grants and personal fees from Ono Pharmaceutical, personal fees from Taiho Pharmaceutical, Boehringer Ingelheim, AstraZeneca. T. Inoue: Grants and personal fees from Ono Pharmaceutical, Bristol-Myers Squibb, personal fees from Chugai Pharmaceutical. K. Nishino: Personal fees from Chyugai, Boehringer Ingelheim, Eli Lilly, AstraZeneca. T. Kumagai: Personal fees from Ono Pharmaceutical, Astra Zeneca, Boehringer Ingelheim. H. Suzuki: Grants from Ono Pharmacetical, personal fees from Taiho Pharmacetical, Boehringer Ingelheim, Pfizer, Eli-Lilly. T. Hirashima: Grants and personal fees from Ono Pharma, Bristol-Myers Squibb, MSD, AstraZeneca, Chugai, Lilly Japan, Boehringer Ingelheim, and grants from Eisai, Daiichi Sankyo, Merck Serono, Taiho, Kyowa Hakko Kirin, Takeda, and personal fees from Bayer. F. Imamura: Grants and personal fees from Ono Pharmaceutical; personal fees from Pfizer, AstraZeneca, Novartis Pharma, Kyowa Hakko Kirin, Boehinger Ingelheim, Taiho Pharmaceutical, Eli Lilly Japan, Chugai Pharceutical, Bristol-Myers Squibb. S. Atagi: Personal fees from Bristol-Myers Squibb, Ono Pharmac, Taiho, Chugai, AstraZeneca, Eli Lilly, Boehringer Ingelheim, and grants from Ono Pharmac, Pfizer, Chugai, AstraZeneca, MSD, Taiho, Yakult Pharmaceutical Industry, Eli Lilly, Boehringer Ingelheim. All other authors have declared no conflicts of interest.