Efficacy and safety of different immunotherapies combined with chemotherapy as first-line therapy in patients with small cell lung cancer: a network meta-analysis

Abstract

Background: The efficacy and safety of different immunosuppressants combined with chemotherapy in treating patients with small-cell lung cancer (extensive-disease small-cell lung cancer, limited-disease small-cell lung cancer and relapsed small-cell lung cancer) are still unknown, and there are no reports directly comparing the efficacy and safety of other immunotherapies.

Objective: This study aimed to compare the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with small-cell lung cancer.

Method: We searched Pubmed, Embase, Cochrane Library, CNKI, and Wanfang databases for relevant articles published from inception to November 11, 2020. The risk of bias of the included studies was conducted using the Cochrane risk-of-bias (RoB) tool. Multiple Bayesian network meta-analyses were performed. They conducted data analysis using R Studio and STATA version 15.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), stability of response (SOR), duration of response (DOR) and adverse events of grade 3 or higher (AE grade≥3). A 95% confidence interval (CI) was provided for each estimate.

Results: This meta-analysis included 16 RCT studies with 5898 patients. For OS, relative to chemotherapy (MD=-4.49; 95%CI [-7.97, -1.03]), durvalumab plus tremelimumab (MD=-4.62; 95%CI [-9.08, -0.11]), ipilimumab (MD=-4.26; 95%CI [-8.01, -0.3]) and nivolumab(MD=-5.66; 95%CI [-10.44, -1.11]) and nivolumab plus ipilimumab (MD=-4.56; 95%CI [-8.7, -0.1]), serplulimab can significantly increase the OS of SCLC patients. There was no significant difference between PFS, SOR and DOR. Analysis of AE showed that different immunotherapy combined chemotherapy regimens were similar to single chemotherapy regarding the overall incidence of AE grade≥3. However, after the cumulative ranking of the common symptoms of different adverse reactions, it was found that nivolumab ranked first in the occurrence probability of anemia (99.08%), fatigue (84.78%), and decreased appetite (89.66%). durvalumab was the most likely in nausea (75.4%). Pembrolizumab (76.24%) was most likely to cause pruritus. Chemotherapy combined with immunotherapy caused less diarrhea than chemotherapy alone (80.16%).

Conclusions: According to our analysis, serplulimab combined with chemotherapy is more likely to show better efficacy with a manageable safety profile for small-cell lung cancer. However, the evidence for this comparison shows some limitations due to the number of literature.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023486053.

Keywords: chemotherapy; immunotherapies; network meta-analysis; serplulimab; small-cell lung cancer.

Figure 1

Flow diagram of studies identified, included and excluded.

Figure 2

Network diagrams of comparisons on various treatments with SCLC. (A) OS; (B) PFS; (C) DOR; (D) SOR; (E) AE grade ≥ 3. Che, chemotherapy; Ate, Atezolizumab; Dur, Durvalumab; DurplusTre, Durvalumab + Tremelimumab; Ipi, Ipilimumab; Pem, Pembrolizumab; Ser, Serplulimab; Niv, Nivolumab; NivplusIpi, Nivolumab + Ipilimumab; Ade, Adebrelimab. PFS, progression-free survival; OS, overall survival; DOR, duration of response; SOR, stable of response; AE grade ≥ 3, adverse events of grade ≥ 3.

Figure 3

Efficacy and safety profiles of the Bayesian network meta-analysis in patients with SCLC. (A) OS; (B) PFS; (C) DOR; (D) SOR; (E) AE grade ≥ 3. Che, chemotherapy; Ate, Atezolizumab; Dur, Durvalumab; DurplusTre, Durvalumab + Tremelimumab; Ipi, Ipilimumab; Pem, Pembrolizumab; Ser, Serplulimab; Niv, Nivolumab; NivplusIpi, Nivolumab + Ipilimumab; PFS, progression-free survival; Ade, Adebrelimab. OS, overall survival; DOR, duration of response; SOR, stable of response; AE grade ≥ 3, adverse events of grade ≥ 3.

Figure 4

Efficacy and safety profiles of the Bayesian network meta-analysis on overall survival in patients with SCLC. (A) HRs and 95% CI for without brain metastases patients. (B) HRs and 95% CI for with brain metastases patients. Che, chemotherapy; Ate, Atezolizumab; Dur, Durvalumab; DurplusTre, Durvalumab + Tremelimumab; Ipi, Ipilimumab; Pem, Pembrolizumab; Ser, Serplulimab; Niv, Nivolumab; NivplusIpi, Nivolumab + Ipilimumab; Ade, Adebrelimab.

Figure 5

Bayesian ranking profiles for immunotherapy combinations on efficacy and safety for patients with SCLC. (A) OS; (B) PFS; (C) DOR; (D) SOR; (E) AE grade ≥ 3. Che, chemotherapy; Ate, Atezolizumab; Dur, Durvalumab; DurplusTre, Durvalumab + Tremelimumab; Ipi, Ipilimumab; Pem, Pembrolizumab; Ser, Serplulimab; Niv, Nivolumab; NivplusIpi, Nivolumab + Ipilimumab; Ade, Adebrelimab. PFS, progression-free survival; OS, overall survival; DOR, duration of response; SOR, stable of response; AE grade ≥ 3, adverse events of grade ≥ 3.

Figure 6

Cluster analysis plots for OS (y-axis) and PFS (x-axis). Atezolizumab; Dur, Durvalumab; DurplusTre, Durvalumab + Tremelimumab; Ipi, Ipilimumab; Pem, Pembrolizumab; Ser, Serplulimab; Niv, Nivolumab; NivplusIpi, Nivolumab + Ipilimumab; Ade, Adebrelimab. PFS, progression-free survival; OS, overall survival.