Original Research Pembrolizumab plus chemotherapy-induced pneumonitis in chemo-nai•ve 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-na & iuml;ve 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 & ordf; 2021 Elsevier Ltd. All rights reserved.

Automated summary

This retrospective cohort study examined the incidence and characteristics of pneumonitis caused by the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors in patients with chemo-naive advanced non-squamous non-small cell lung cancer. The study found that treatment-related pneumonitis occurred at a higher rate in the real-world population and led to worse survival outcomes, emphasizing the need for further attention and research to improve the safety of this combination therapy.