The association between the incidence risk of pneumonitis and PD-1/PD-L1 inhibitors in advanced NSCLC: A meta-analysis of randomized controlled trials

Objective: Immune checkpoint inhibitors (ICIs) have shown a significant efficacy for patients with non-small cell lung cancer (NSCLC). However, checkpoint inhibitor pneumonitis (CIP) is a rare but severe and life-threatening adverse event. Hence, we performed a systematic review and meta-analysis to evaluate the incidence and risk of CIP in patients with NSCLC. Methods: Pubmed, Embase, Cochrane Library and ClinicalTrials.gov (http://clinicaltrials.gov/) were searched up to December 15, 2020. Studies regarding all-grade and high-grade pneumonitis were included. The data was analyzed using meta-packages of R 3.6.0. Results: A total of sixteen randomized controlled trials including 9500 patients were identified for further evaluation. The overall incidence of all-grade and high-grade CIP was 4.17% and 2.02%, respectively. Compared with conventional chemotherapy, patients treated with ICIs significantly increased risk of all-grade (RR: 4.11, p < 0.0001) and high-grade (RR: 3.16, p < 0.0001) pneumonitis. Subgroup analysis showed the ICIs combined with chemotherapy was associated with a higher incidence of CIP than monotherapy alone (6.03% vs 3.32%, p = 0.01). And the rate of death owing to CIP was higher than chemotherapy-mediated pneumonitis. Conclusion: There were a higher incidence and risk of pneumonitis with the application of ICIs when compared with chemotherapy. Higher mortality rate of pneumonitis was more frequent in ICIs group. Thus, early detection, proper administration and optimal management are needed for physicians prevent potentially CIP deterioration.

Automated summary

A systematic review and meta-analysis on 16 randomized controlled trials revealed that the incidence and risk of CIP in NSCLC patients were higher with ICIs compared to chemotherapy. Combination therapy of ICIs with chemotherapy showed a higher incidence of CIP and higher mortality rate compared to monotherapy. Early detection, proper administration, and optimal management are crucial in preventing potential CIP deterioration.