A Meta-analysis Of The Efficacy And Safety Of Immune Checkpoint Inhibitors In The Treatment Of Small Cell Lung Cancer

Objective: Immune checkpoint inhibitors(ICIs),as a kind of new therapy of malignancies,greatly improve survival benifits of patients.However,for patients with small-cell-lung cancer(SCLC),the efficacy and safety of ICIs need to be further evaluated.Methods:A systematic search of two major English databases,including the Pub Med and the Cochrane Library was conducted.Furthermore,abstracts listing from major oncology conference proceedings,including the American Society of Clinical Oncology,the European Society of Medical Oncology and the World Conference on Lung Cancer meetings were browsed from 2018 to2020.The clinical trials that meet included criteria were included.We extracted and analysed the main outcomes of the literature such as: hazard ratio with 95% confidence interval(CI)for overall survival(OS)and progression-free survival(PFS),objective response rate(ORR),and the incidence of adverse events(AEs).We used STATA 15.0 to complete the analysis of data.Results: We included a total of 16 studies comprising 4,476 patients.We found the magnitude of efficacy for ICIs as first-line therapy had statistically significant benefits in OS(0.82,95% CI:0.76-0.89,P<0.001)and PFS(0.80,95%CI: 0.74-0.86,P<0.001)compared to chemotherapy alone.But for ORR,the results were not statistically significant.As for second-line treatment,the effect of ICIs monotherapy was not better than chemotherapy for OS,PFS or ORR.When ICIs were used for maintenance therapy,we found that ICIs were only effective for PFS(0.69,95% CI: 0.61-0.79,P<0.001).At the same time,we performed a subgroup analysis for OS based on the baseline characteristics of the patien ts.The results found that for patients with brain metastasis and those who do not smoke,ICIs did not significantly improve OS.With regard to safety,ICIs did not bring the increased incidence of AEs to patients.For grades 3-4 AEs,the pooled odds ratio(OR)was 1.35(95% CI: 0.58-3.15;P=0.484),and for all grades of AEs,the OR was 1.36(95% CI: 0.50-3.70;P=0.543).AEs were mostly digestive system and blood system toxicities,and serious AEs are relatively rare.Conclusions:For the first-line treatment of SCLC,the effect of ICIs combined with chemotherapy had survival benifits,but the benifits of ICIs was not obvious for maintenance and second-line treatment.In terms of safety,ICIs did not increase the incidence of AEs.However,our research also has limitations,and clinical studies are still needed to continue exploring this field.