Pembrolizumab plus chemotherapy-induced pneumonitis in chemo-naïve patients with non-squamous non-small cell lung cancer: A multicentre, retrospective cohort study.
INTRODUCTION
Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings.


METHODS
We conducted a 36-centre, retrospective cohort study in patients with chemo-naïve advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019.


RESULTS
The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9-16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6-6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4-10.5) and 9 patients (3.0%, 95% CI 1.4-5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0-6.8) and 7.5 (95% CI 6.5-8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07-3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12-8.20, P = 0.03).


CONCLUSIONS
Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy.


TRIAL REGISTRATION NUMBER
UMIN000038084.
['Fujimoto|Daichi|D|', 'Miura|Satoru|S|', 'Yoshimura|Kenichi|K|', 'Wakuda|Kazushige|K|', 'Oya|Yuko|Y|', 'Yokoyama|Toshihide|T|', 'Yokoi|Takashi|T|', 'Asao|Tetsuhiko|T|', 'Tamiya|Motohiro|M|', 'Nakamura|Atsushi|A|', 'Yoshioka|Hiroshige|H|', 'Haratani|Koji|K|', 'Teraoka|Shunsuke|S|', 'Tokito|Takaaki|T|', 'Murakami|Shuji|S|', 'Tamiya|Akihiro|A|', 'Itoh|Shoichi|S|', 'Yokouchi|Hiroshi|H|', 'Watanabe|Satoshi|S|', 'Yamaguchi|Ou|O|', 'Tomii|Keisuke|K|', 'Yamamoto|Nobuyuki|N|']
D000368:Aged D061067:Antibodies, Monoclonal, Humanized D000971:Antineoplastic Combined Chemotherapy Protocols D002289:Carcinoma, Non-Small-Cell Lung D005260:Female D006801:Humans D000082082:Immune Checkpoint Inhibitors D015994:Incidence D007564:Japan D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D011014:Pneumonia D000077982:Progression-Free Survival D012189:Retrospective Studies D018570:Risk Assessment D012307:Risk Factors D013997:Time Factors D016896:Treatment Outcome
Pneumonitis Non-small cell lung cancer Immune checkpoint inhibitor PD-1 PD-L1 Pneumonia