Efficacy and safety of immunotherapy combined with chemotherapy in patients with ES-SCLC: A systematic review and network meta-analysis of RCTs and RWSs

Abstract

Objectives: To evaluate the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors in the treatment of extensive-stage small-cell lung cancer (ES-SCLC), we conducted a systematic review and meta-analysis that included randomized controlled trials (RCTs) and real-world studies (RWS).

Methods: By scanning PubMed, Web of science, Embase, and other relevant clinical information public databases, nine RCTs and eight RWSs involving 5205 patients were included in the study. We directly compared the differences between chemotherapy and PD-1/PD-L1 inhibitors plus chemotherapy, and determined the optimal treatment strategy through network meta-analysis (NMA).

Results: Compared to chemotherapy, the addition of PD-1/PD-L1 inhibitors significantly improves the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in SCLC patients. Regarding safety, both RCTs and RWSs indicated no significant difference in grade 3-4 adverse events between chemotherapy and chemoimmunotherapy. NMA showed serplulimab plus chemotherapy (Serp_Chemo) appears to provide the best OS, PFS, and ORR benefit, while nivolumab plus chemotherapy shows higher toxicity than other regimens. In subgroup analysis, for elderly patients (age ≥65) and non-elderly (age <65) patients, the most promising quality regimens for achieving better OS extension are atezolizumab plus chemotherapy (Atez_Chemo) and Serp_Chemo, respectively. For patients with PD-L1 ≥ 1% and lactate dehydrogenase (LDH) > upper limit of normal (ULN), there is no apparent OS benefit from immune therapy.

Conclusions: In ES-SCLC treatment, adding PD-1/PD-L1 inhibitors to standard chemotherapy improves OS, PFS, and ORR, with Serp_Chemo shows the most promise. Atez_Chemo and Serp_Chemo provided better survival for elderly and non-elderly patients, respectively.

Keywords: elderly; extensive stage small cell lung cancer; immune checkpoint inhibitors; meta‐analysis.

FIGURE 1

Study selection.

FIGURE 2

Forest plot of overall survival (OS) and progression‐free survival (PFS) for the total population. (a) Forest plot of OS in randomized controlled trials (RCTs) and real‐world studies (RWSs) between PD‐1/PD‐L1 combined with chemo and chemo alone. (b) Forest plot of PFS in RCTs and RWSs between ICIs combined with chemo and chemo alone. Chemo, chemotherapy; ICIs, immune checkpoint inhibitors; PD‐1, programmed death‐1 inhibitors; PD‐L1, programmed death‐ligand 1 inhibitors.

FIGURE 3

Efficacy and safety profiles of the Bayesian network meta‐analysis in all patients with ES‐SCLC. (a) Hazard ratios and 95% CIs for overall survival (upper triangle in blue) and progression‐free survival (lower triangle in yellow). (b) ORs and 95% CIs for objective response rate (upper triangle in blue) and grade 3–4 AEs (lower triangle in yellow). Adeb_chemo, adebrelimab plus chemotherapy; AEs, adverse events; Atez_chemo, atezolizumab plus chemotherapy; Chemo, chemotherapy; CIs, confidence intervals; Durv_chemo, durvalumab plus chemotherapy; ES‐SCLC, extensive‐stage small cell lung cancer; Nivo_chemo, nivolumab plus chemotherapy; ORs, odds ratios; Pemb_chemo, pembrolizumab plus chemotherapy; Serp_chemo, serplulimab plus chemotherapy; Tisl_chemo, tislezumab plus chemotherapy; Tori_chemo, toripalimab plus chemotherapy.

FIGURE 4

Bayesian ranking profiles for immunotherapy combinations on efficacy and safety for all patients with ES‐SCLC. Ranking plots show OS, PFS, ORR, and grade 3–4 AEs ranked from first to last, respectively, with the vertical axis representing probability (%) and the horizontal axis representing rank. AEs, adverse events; ES‐SCLC, extensive‐stage small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression‐free survival.

FIGURE 5

OS and PFS for Bayesian network meta‐analysis of age subgroups. (a) Hazard ratios and 95% CIs for overall survival in age ≥65 patients (upper triangle in blue) and age (lower triangle in yellow). (b) ORs and 95% CIs for objective response rate (upper triangle in blue) and grade 3–4 AEs (lower triangle in yellow). Adeb_chemo, adebrelimab plus chemotherapy; AEs, adverse events; Atez_chemo, atezolizumab plus chemotherapy; Chemo, chemotherapy; CIs, confidence intervals; Durv_chemo, durvalumab plus chemotherapy; Nivo_chemo, nivolumab plus chemotherapy; ORs, odds ratios; OS, overall survival; Pemb_chemo, pembrolizumab plus chemotherapy; PFS, progression‐free survival; Serp_chemo, serplulimab plus chemotherapy; Tisl_chemo, tislezumab plus chemotherapy.