The incidence of gastrointestinal adverse events in patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1 inhibitors: a meta-analysis

Background: We conducted a meta-analysis to evaluates the incidence of the gastrointestinal (GI) adverse events with the use of PD-1 inhibitors among patients with advanced non-small cell lung cancer (NSCLC). Methods: The PICOs (participants, intervention, comparison, and outcomes) elements were used for the selection of studies to meet the inclusion and exclusion criteria. Google Scholar, PubMed, Science Direct and proceedings of major oncology conferences were systematically searched from their inception to December 2020, to identify studies which reported the GI adverse events of PD-1 inhibitors among patients with NSCLC. Risks of bias were assessed by using a revised methodological index for nonrandomized studies (MINORS). Pooled incidences and weighted relative risk (RR) estimate for GI adverse events, the incidence of treatment discontinuation due to GI adverse events was also calculated. To perform the analysis of qualified studies, the model of random effects was used and the inconsistency of studies with the I2 index was investigated. OpenMeta 10.10, Stata 11.0 and RevMan 5.3 software were used for data analysis. Results: The research included 15 studies comprising of a total of 3,716 patients. The incidences of all grade GI symptoms were: diarrhea 8.6% (95% CI: 6.6-10.6%), nausea 9.2% (95% CI: 7.3-11.0%), vomiting 3.2% (95% CI: 1.9-4.5%), constipation 2.8% (95% CI: 1.8-3.9%), colitis 0.7% (95% CI: 0.4-1.1%), stomatitis (95% CI: 1.0-2.7%), and decreased appetite 10.0% (95% CI: 8.3-11.7%). Therapy using PD-1 inhibitors was discontinued in 2.5% (95% CI: 0.0-5.1%) of patients with nausea, in 3.0% (95% CI: 0.7- 5.3%) of those with diarrhea, and in 45.7% (95% CI: 20.6-70.7%) of patients with colitis. Compared with chemotherapy, the use of PD-1 inhibitors showed significant increase in the occurrence of grade 1-4 colitis (RR =3.90, 95% CI: 1.41-10.81, P=0.009) and grade 3-4 colitis (RR =3.76, 95% CI: 1.07-13.26, P=0.04). Discussion: This meta-analysis provides a reliable estimate of the incidences of GI adverse events among NSCLC patients. Especially when colitis does occur, it often results in therapy discontinuation. Use of PD-1 inhibitors led to a higher incidence of colitis as compared to the use of chemotherapy.