Abstract:

In the present study, we aimed to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) in treating malignant pleural mesothelioma (MPM). The PubMed, Embase, Web of science, and Cochrane Library databases were searched for prospective clinical trials evaluating the efficacy and safety of ICIs for the treatment of advanced MPM. The primary outcomes included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Eight single-arm studies and three randomized controlled trials were included, including 839 patients. Meta-analysis results showed that the pooled overall ORR of the studies receiving ICIs was 37% (95% confidence interval (CI), 23%–51%), the median OS was 14.02 months (95% CI, 11.40–17.64 months), and the median PFS was 4.72 months (95% CI, 3.62–6.16 months). Subgroup analysis was made according to the type of treatment methods: ICI single-agent immunotherapy or ICI combination therapy (combining ICIs or ICI with chemotherapy). It was suggested that the combination therapy of ICI was superior to the single-agent immunotherapy of ICI in ORR, OS, and PFS. The results were ORR 51% (95% CI, 39%–62%) vs. 19% (95% CI, 8%–29%), OS 18.30 months (95% CI, 16.42–20.40 months) vs. 11.03 months (95% CI, 9.46–12.86 months), and PFS 6.78 months (95% CI, 6.18–7.44 months) vs. 3.40 months (95% CI, 2.41–4.79 months). The incidence of grade 3–4 AEs in all studies was 30%. The most common AEs of ICI treatment were fatigue, diarrhea, and rash. The level 3–4 AEs of the combination group were higher than those of the single-agent group (37% vs. 22%). The combination therapy of ICI had clinical application value in MPM patients and supported large-scale clinical application in MPM patients. However, regarding safety, ICI combination therapy had a higher incidence of grade 3–4 AEs than first-line chemotherapy.

Key words: Malignant pleural mesothelioma, Immune checkpoint inhibitors, CTLA-4, PD-1/PD-L1, Systematic review