Dataset Information

Comparison of atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with extensive-stage small cell lung cancer: A systematic review and network meta-analysis.

ABSTRACT:

Background

In recent years, immune checkpoint inhibitors (ICIs) including atezolizumab, durvalumab, pembrolizumab, and nivolumab have reported their efficacy and safety profile in patients with extensive-stage small cell lung cancer (ES-SCLC). However, given the diverse efficacy and inconsistent safety among the ICIs, with the absence of head-to-head researches designed to evaluate the efficacy among them, it might bring with confusion on selection in clinical practice.

Objectives

The present systematic review and network meta-analysis was performed to conduct indirect comparisons on efficacy and safety profile among ICIs, including atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with ES-SCLC.

Design

Several databases were retrieved with established criteria until June 20, 2020, with the main MeSH Terms and their similarities. Hazard ratios of overall survival (OS) and progression-free survival (PFS), odds ratios (ORs) of disease control rate (DCR), objective response rate (ORR), and adverse events (AEs) were compared indirectly with network meta-analysis.

Data sources

Medline, Cochrane library, and Embase.

Eligibility criteria

Prospective, randomized, controlled clinical studies, which reported PFS, OS, and AEs.

Data extraction and synthesis

Clinical characteristics were extracted by the 2 authors independently. Comparisons of HRs were calculated for PFS and OS by random effect model. ORR, DCR, and AEs were presented with ORs. Based on surface under the cumulative ranking curve, and forest plots, efficacy and safety of the treatments were ranked, with predicted histogram described.

Results

In total, there were 4 studies including 1547 patients who met the eligibility criteria and enrolled. For indirect comparisons, no significant difference on PFS was observed between atezolizumab and durvalumab (HR 0.96, 95% CI, 0.72-1.29), or between atezolizumab and pembrolizumab (HR 1.05, 95% CI, 0.78-1.43), or between atezolizumab and nivolumab (HR 1.18, 95% CI, 0.79-1.79), or between durvalumab and pembrolizumab (HR 1.10, 95% CI, 0.84-1.43). or between durvalumab and nivolumab (HR 1.23, 95% CI, 0.83-1.82), or between pembrolizumab and nivolumab (HR 1.12, 95% CI, 0.76-1.66), nor significant difference on OS observed between atezolizumab and durvalumab (HR 0.93, 95% CI, 0.67-1.30), or between atezolizumab and pembrolizumab (HR 0.88, 95% CI, 0.62-1.24), or between atezolizumab and nivolumab (HR 1.04, 95% CI, 0.66-1.66), or between durvalumab and pembrolizumab (HR 0.94, 95% CI, 0.70-1.25), or between durvalumab and nivolumab (HR 1.12, 95% CI, 0.73-1.71), or between pembrolizumab and nivolumab (HR 1.19, 95% CI, 0.77-1.84). However, durvalumab was shown statistical superiority on ORR when compared with atezolizumab (HR 0.79, 95% CI, 0.64-0.98), also with significantly higher risk on immune-related AEs when compared with atezolizumab (OR 0.22, 95% CI, 0.10-0.50), and pembrolizumab (OR 3.12, 95% CI, 1.27-7.64).

Conclusions

Results of the study revealed that there was no statistical difference on PFS or OS among agents of atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with ES-SCLC. However, durvalumab was shown superiority on ORR when compared with atezolizumab, also with significantly higher risk on immune-related AEs.

SUBMITTER: Chen J

PROVIDER: S-EPMC8051984 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: This study evaluated the cost-effectiveness of atezolizumab + chemotherapy vs. chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (SCLC) in the United States (US). Methods: The three health states partitioned survival (PS) model was used over the lifetime. Effectiveness and safety data were derived from the IMpower133 trial. The parametric survival model and mixture cure model were used for the atezolizumab + chemotherapy group to explore the long-term uncertainty of the effect of immunotherapy, and the parametric survival model was used for the chemotherapy group. Costs were derived from the pricing files of Medicare and Medicaid Services, and utility values were derived from previous studies. Sensitivity analyses were performed to observe model stability. Results: If the mixture cure model was considered for the intervention group, compared with chemotherapy alone, atezolizumab + chemotherapy yielded an additional 0.11 quality-adjusted life-years (QALYs), with an incremental cost of US$84,257. The incremental cost-utility ratio (ICUR) was US$785,848/QALY. If the parametric survival model was considered for the intervention group, atezolizumab + chemotherapy yielded an additional 0.10 QALYs, with an incremental cost of US$84,257; the ICUR was US$827,610/QALY. In the one-way sensitivity analysis, progression-free (PF) and postprogression (PP) utilities were the main drivers. In the scenario analysis (PF utility = 0.673, PP utility = 0.473), the results showed that the ICUR was US$910,557/QALY and US$965,607/QALY when the mixture cure model and parametric survival model was considered for the intervention group, respectively. In the PSA, the probabilities that atezolizumab + chemotherapy would not be cost-effective were 100% if the willingness-to-pay threshold was US$100,000/QALY. Conclusions: The findings of the present analysis suggest that atezolizumab + chemotherapy is not cost-effective in patients receiving first-line treatment for extensive-stage SCLC in the US.

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Project description:BackgroundThe latest published CASPIAN trial demonstrated that adding durvalumab to etoposide and platinum (EP) improved survival dramatically for patients with extensive-stage small cell lung cancer (ES-SCLC). Considering the high cost of durvalumab, this study evaluated the cost-effectiveness of durvalumab plus EP (DEP) in the first-line setting for treatment-naïve patients with ES-SCLC from the U.S. payer perspective.Materials and methodsWe developed a three-state Markov model to simulate the disease course and source consumption of ES-SCLC over a lifetime horizon. Pseudo-individual patient-level data were generated from digitized Kaplan-Meier curves. Direct medical costs, including drug and administration costs, disease management and adverse events treatment fees, best supportive care and terminal care costs were obtained from sources including the Centers for Medicare and Medicaid Services, Healthcare Cost and Utilization Project, and relevant literature. Health state utility values were derived from published literature. Main outcomes considered were total costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). All costs were adjusted for inflation to reflect 2019 U.S. dollars. The willingness-to-pay threshold was set as $150,000/QALY. One-way and probabilistic sensitivity analyses were used to explore the uncertainty of model assumptions.ResultsCompared with EP, DEP was projected to increase life expectancy by 0.86 LYs (1.73 vs. 0.87) and 0.44 QALYs (0.93 vs. 0.49). The incremental treatment cost was $95,907, and the corresponding ICER was $216,953/QALY. The result was most sensitive to the variation of durvalumab acquisition cost. Probabilistic sensitivity analysis revealed that the probability of DEP over EP regimen to be cost-effective was 9.4% at a willingness-to-pay threshold of $150,000/QALY. In the case of reducing the price of durvalumab by 30.7%, DEP was more cost-effective than EP.ConclusionFrom the perspective of the U.S. payer, adding durvalumab to EP is estimated to be not cost-effective compared with EP alone for patients with untreated ES-SCLC.Implications for practiceThe information provided by this analysis serves as a reference for decision makers. Lowering the price of durvalumab would be a potential measure to improve the economics of durvalumab plus etoposide and platinum (DEP), and the inclusion of durvalumab in the Medicare pharmacopeia could make DEP more economically available. These results may also guide physicians and patients to choose the most economically feasible treatment.