Comparison of the checkpoint inhibitor pneumonitis incidence between immunotherapy alone or in combination with chemotherapy for lung cancer: An observational, retrospective pharmacovigilance study.

2655 Background: Clinical trials lack direct cross-comparison in safety between immune checkpoint inhibitor (ICI) as monotherapy and in combination with chemotherapy. The adverse event of checkpoint inhibitor pneumonitis (CIP) is an important factor influencing the treatment decision making. We performed a real-world pharmacovigilance study in the US Food and Drug Administration Adverse Event Reporting System (FAERS) to determine if ICI combination therapy is superior to monotherapy for lung cancer patients in terms of CIP incidence. Methods: The database of lung cancer patients receiving ICI between 2015 and 2020 was extracted for this study. The strategy-specific durations of the pneumonitis event were compared using the Kaplan-Meier method. Reporting odds ratio (ROR), a surrogate measure in disproportionality analysis, was used to assess the signal of CIP between ICI treatment strategies. Results: A total of 27,882 lung cancer patients with reported adverse events were involved. Among them, 1763 (6.3%) CIP after ICIs therapy were identified. In general, ICI usage was associated with over-reporting frequencies of CIP, but this association was no longer significant after adjustment (ROR: 1.14, 95%CI 0.86-1.49). The median times to CIP occurred early after therapy onset, either in ICI monotherapy or in combination with chemotherapy (41 days and 37 days, log-rank p>0.05). Different reporting frequencies emerged when we further compared different ICI strategies. Combination therapy with anti-PD-1 and chemotherapy was associated with a higher CIP incidence compared with anti-PD-1 monotherapy (ROR: 1.86, 95%CI 1.37-2.51), whereas anti-PD-L1/ CTLA-4 medications had lower risks in combination with chemotherapy (ROR: 0.31, 95%CI 0.16-0.56 and ROR: 0.41, 95%CI 0.09-1.22). Subgroup analyses on those with recorded therapy duration also indicated that reports of CIP were significantly lower with combination therapy of PD-L1 and CTLA-4 (ROR: 0.52, 95%CI 0.36-0.74 and ROR: 0.22, 95%CI 0.09-0.51 respectively). Conclusions: Compared with ICI monotherapy, the combination with chemotherapy might have an acceptable risk of CIP. Anti-PD-1 medications with additional chemotherapy could increase the risk of pneumonitis, whereas the risk was lower in the combination strategy with anti-PD-L1/CTLA-4. The combination might be a better therapeutic strategy than ICI monotherapy in treating lung cancer, regarding the CIP incidence. [Table: see text]