First-Line Treatments for Extensive-Stage Small-Cell Lung Cancer With Immune Checkpoint Inhibitors Plus Chemotherapy: A Network Meta-Analysis and Cost-Effectiveness Analysis

Abstract

BackgroundImmune checkpoint inhibitors (ICIs) plus chemotherapy were unlikely to be considered cost-effective compared with chemotherapy as the first-line treatment of patients with extensive-stage small-cell lung cancer (ES-SCLC) in China due to its high costs. However, the cost-effectiveness of the comparison between the regimens of ICIs plus chemotherapy were remained unclear yet. The aim of this study was to evaluate the efficacy and cost-effectiveness of ICIs plus chemotherapy as the first-line treatment for ES-SCLC from the perspective of the Chinese healthcare system.MethodsA network meta-analysis (NMA) was conducted to indirect compare the clinical benefits between the ICIs plus chemotherapy regimens. A decision-analytic model was established to evaluate the cost-effectiveness from the Chinese healthcare system, the clinical efficacy and safety data were obtained from the clinical trials and the results of NMA. Cost and utility values were gathered from the local charges and previously studies. Key outputs of the NMA were overall survival (OS) and progression-free survival (PFS). Incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed to explore the robustness of the model outcomes.ResultsFive clinical trials (IMpower133, CASPIAN, KEYNOTE-604, CA184-156, and EA5161) of 1,255 patients received first-line ICIs plus chemotherapy strategies were analyzed in the NMA. NMA showed that nivolumab plus chemotherapy was ranked higher than other strategies. The cost-effectiveness analysis showed that atezolizumab plus chemotherapy achieved relatively higher health benefits and lower costs. One-way sensitivity analyses revealed that the cost of ICIs had the substantial impact on model outcomes. The probabilistic sensitivity analyses suggested that the probability of atezolizumab plus chemotherapy could be considered cost-effective was more than 50% at the willingness-to-pay (WTP) threshold of $31,313/QALY in China. In scenario analyses, when the price of nivolumab reduced 80%, the probability of nivolumab plus chemotherapy being cost-effective was more than 50%.ConclusionsThe NMA and cost-effectiveness revealed that atezolizumab plus chemotherapy is the most favorable first-line treatment for previously untreated ES-SCLC patients compared other ICIs plus chemotherapy regimens in China. The price reduction of nivolumab would make nivolumab plus chemotherapy be the most cost-effective option in future possible context.

Cost-effectiveness analysis of adebrelimab combined with chemotherapy for extensive-stage small cell lung cancer

“…It should be pointed out that apart from body weight, body surface area, and creatinine clearance, no other parameters can affect the cost of drugs. As the relevant data on the quality of life were not available in the CAPSTONE-1 trial ( Wang et al, 2022 ), the utility of PFS and PD was assessed from published literature in China ( Table 1 ) ( Kang et al, 2021 ). We considered the disutility of adverse reactions of grade 3 or higher with an incidence greater than 5% to reduce the impact of using the same utility values for both treatment groups in the model.…”

“…Immune checkpoint inhibitors (ICIs) reduce immunosuppression in the tumor microenvironment and reactivate the anti-tumor function of T cells by inhibiting cytotoxic T lymphocyte-associated protein 4 and programmed cell death-1 pathway/programmed cell death receptor ligand-1 (PD-L1) ( Kang et al, 2021 ). ICIs yield effective results in ES-SCLC treatment ( Horn et al, 2018 ; Paz-Ares et al, 2019 ; Rudin et al, 2020 ), bringing new hope for survival among patients with ES-SCLC.…”

Atezolizumab (Tecentriq)

“…The ITC by Kang et al ( 2021) 40 included 5 trials in the network, of which 4 were identical to those included in the sponsor's NMA. Risk of bias was assessed, and a key limitation identified was the absence of subgroup analyses.…”

“…Of the 9 published ITCs assessed in the CADTH review, 4(Ando et al [2021] 39 ;Kang et al [2021] 40 ;Gristina et al [2021] 41 ;Zhou et al [2020] 42 ) used Bayesian methods to conduct the NMA, 3(Chen et al [2021] 43 ;Chen HL et al [2020] 44 ;Wang et al [2020] 45 ) reported a frequentist approach, and the rest did not specify clearly the NMA methods used in the ITC. None of the studies reported the priors used in conducting the NMA.…”

“…None of the studies reported the priors used in conducting the NMA. Only 1 study(Kang et al [2021] 40 ) reported information on the assessment of model fit. Consistency assessments were reported for some studies, most of which used the I 2 statistics to assess heterogeneity between the trials included in the network.…”