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Review
. 2024 Sep 9:14:1397960.
doi: 10.3389/fonc.2024.1397960. eCollection 2024.

Efficacy and safety evaluation of first-line systemic treatments for unresectable esophageal squamous cell carcinoma: a network meta-analysis

Huiling Shi  1   2 , Yong Tan  3 , Chao Ma  1   2 , Yushan Wei  1   2 , Fengling Shi  1   2 , Juan Wang  1   2 , Caihua Xu  4 , Rongrui Liang  1   2   4
Affiliations
Review

Efficacy and safety evaluation of first-line systemic treatments for unresectable esophageal squamous cell carcinoma: a network meta-analysis

Huiling Shi et al. Front Oncol. .

Abstract

Objective: To evaluate the efficacy and safety of various first-line initial treatment systemic regimens for patients with unresectable esophageal squamous carcinoma(ESCC), utilizing a network meta-analysis approach.

Methods: A comprehensive search for randomized controlled trials focusing on the primary treatment of esophageal cancer ESCC was conducted across multiple databases including PubMed, Embase, Cochrane Library, and Web of Science, up until November 17, 2023. The quality of the included studies was rigorously assessed using Review Manager software. Subsequently, data analysis was meticulously carried out employing R software. The first-line treatment regimens examined were: CD (Cisplatin + Docetaxel), CET-CF (Cetuximab + Cisplatin + Fluorouracil), CF (Cisplatin + Fluorouracil), N-CF (Nivolumab + Cisplatin + Fluorouracil), NI (Nivolumab + Ipilimumab), Nim-CF (Nimotuzumab + Cisplatin + Fluorouracil), P-CF (Pembrolizumab + Cisplatin + Fluorouracil), and Ser-CF (Serplulimab + Cisplatin + Fluorouracil). The Primary endpoints included the overall survival(OS),progression-free survival (PFS),objective response rate (ORR) and disease control rate (DCR).The secondary endpoint was adverse effects(AEs).

Results: The analysis encompassed eight studies, incorporating a total of 3,051 patients with untreated esophageal cancer. There are 45 people in the CD regimen,32 in the CET-CF regimen,1,212 in the CF regimen,447 in the N-CF regimen,456 in the NI regimen,53 in the Nim-CF regimen,447 in the P-CF regimen and 368 in the Ser-CF regimen. The network meta-analysis revealed that, in comparison to the CF regimen, the other regimens (CD, CET-CF, N-CF, NI, Nim-CF, P-CF, and Ser-CF) did not demonstrate a statistically significant impact on overall survival (OS) or progression-free survival (PFS). However, Ser-CF potentially offers superior outcomes in terms of OS and PFS when juxtaposed with other regimens. Notably, N-CF was associated with a substantial increase in the objective response rate (ORR), and CET-CF markedly improved the disease control rate (DCR). In terms of adverse effects, N-CF was more likely to cause anorexia, whereas CET-CF was significantly associated with nausea, vomiting, neutropenia, and skin disorders.

Conclusion: The current evidence suggests that N-CF may provide the most favorable outcomes in terms of ORR, while CET-CF could be the optimal choice for enhancing DCR in patients with untreated esophageal cancer.

Keywords: advanced esophageal squamous carcinoma; efficacy; first-line systemic treatments for esophageal cancer first-line treatment; network meta-analysis; safety.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Literature search flowchart.
Figure 2
Figure 2
Risk of bias graph.
Figure 3
Figure 3
Risk of bias summary.
Figure 4
Figure 4
Meta-Analysis of Overall Survival (OS). (A) Network Plot(Each circle represents a different intervention, with the size of the circle proportional to the number of people in that intervention, and the line between the circles represents the existence of a direct comparison between the two interventions, with the thickness of the line representing the proportional number of studies), (B) Area under the Cumulative Probability Curve(Surface Under the Cumulative Ranking Curve of different intervention, CD, Cisplatin + Docetaxel; CF, Cisplatin + Fluorouracil; NI, Nivolumab + Ipilimumab,P-CF, Pembrolizumab + Cisplatin + Fluorouracil,CET-CF, Cetuximab + Cisplatin + Fluorouracil,N-CF, Nivolumab + Cisplatin + Fluorouracil,Nim-CF, Nimotuzumab + Cisplatin + Fluorouracil,Ser-CF, Serplulimab + Cisplatin + Fluorouracil); (C) Forest Plot.
Figure 5
Figure 5
Meta-Analysis of Progression-Free Survival (PFS). (A) Network Plot(Each circle represents a different intervention, with the size of the circle proportional to the number of people in that intervention, and the line between the circles represents the existence of a direct comparison between the two interventions, with the thickness of the line representing the proportional number of studies), (B) Area under the Cumulative Probability Curve (Surface Under the Cumulative Ranking Curve of different intervention, CD, Cisplatin + Docetaxel; CF, Cisplatin + Fluorouracil; NI, Nivolumab + Ipilimumab,P-CF, Pembrolizumab + Cisplatin + Fluorouracil,CET-CF, Cetuximab + Cisplatin + Fluorouracil,N-CF, Nivolumab + Cisplatin + Fluorouracil,Ser-CF, Serplulimab + Cisplatin + Fluorouracil), (C) Forest Plot.
Figure 6
Figure 6
Meta-Analysis of Objective Response Rate (ORR). (A) Network Plot(Each circle represents a different intervention, with the size of the circle proportional to the number of people in that intervention, and the line between the circles represents the existence of a direct comparison between the two interventions, with the thickness of the line representing the proportional number of studies), (B) Area under the Cumulative Probability Curve (Surface Under the Cumulative Ranking Curve of different intervention, CD, Cisplatin + Docetaxel; CF, Cisplatin + Fluorouracil; NI, Nivolumab + Ipilimumab,P-CF, Pembrolizumab + Cisplatin + Fluorouracil,CET-CF, Cetuximab + Cisplatin + Fluorouracil,N-CF, Nivolumab + Cisplatin + Fluorouracil,Ser-CF, Serplulimab + Cisplatin + Fluorouracil), (C) Forest Plot.
Figure 7
Figure 7
Meta-Analysis of Disease Control Rate (DCR). (A) Network Plot(Each circle represents a different intervention, with the size of the circle proportional to the number of people in that intervention, and the line between the circles represents the existence of a direct comparison between the two interventions, with the thickness of the line representing the proportional number of studies), (B) Area under the Cumulative Probability Curve(Surface Under the Cumulative Ranking Curve of different intervention, CD, Cisplatin + Docetaxel; CF, Cisplatin + Fluorouracil; NI, Nivolumab + Ipilimumab; CET-CF, Cetuximab + Cisplatin + Fluorouracil,N-CF, Nivolumab + Cisplatin + Fluorouracil,Ser-CF, Serplulimab + Cisplatin + Fluorouracil), (C) Forest Plot.
Figure 8
Figure 8
Meta-Analysis of Neutropenia. (A) Network Plot(Each circle represents a different intervention, with the size of the circle proportional to the number of people in that intervention, and the line between the circles represents the existence of a direct comparison between the two interventions, with the thickness of the line representing the proportional number of studies), (B) Area under the Cumulative Probability Curve (Surface Under the Cumulative Ranking Curve of different intervention, CF, Cisplatin + Fluorouracil; NI, Nivolumab + Ipilimumab,P-CF, Pembrolizumab + Cisplatin + Fluorouracil,CET-CF, Cetuximab + Cisplatin + Fluorouracil,N-CF, Nivolumab + Cisplatin + Fluorouracil,Nim-CF, Nimotuzumab + Cisplatin + Fluorouracil,Ser-CF, Serplulimab + Cisplatin + Fluorouracil), (C) Forest Plot.
Figure 9
Figure 9
Meta-Analysis of Nausea. (A) Network Plot(Each circle represents a different intervention, with the size of the circle proportional to the number of people in that intervention, and the line between the circles represents the existence of a direct comparison between the two interventions, with the thickness of the line representing the proportional number of studies), (B) Area under the Cumulative Probability Curve(Surface Under the Cumulative Ranking Curve of different intervention, CF, Cisplatin + Fluorouracil; NI, Nivolumab + Ipilimumab,P-CF, Pembrolizumab + Cisplatin + Fluorouracil,CET-CF, Cetuximab + Cisplatin + Fluorouracil,N-CF, Nivolumab + Cisplatin + Fluorouracil,Nim-CF, Nimotuzumab + Cisplatin + Fluorouracil,Ser-CF, Serplulimab + Cisplatin + Fluorouracil), (C) Forest Plot.
Figure 10
Figure 10
Meta-Analysis of SKIN. (A) Network Plot(Each circle represents a different intervention, with the size of the circle proportional to the number of people in that intervention, and the line between the circles represents the existence of a direct comparison between the two interventions, with the thickness of the line representing the proportional number of studies), (B) Area under the Cumulative Probability Curve(Surface Under the Cumulative Ranking Curve of different intervention, CF, Cisplatin + Fluorouracil; NI, Nivolumab + Ipilimumab,P-CF, Pembrolizumab + Cisplatin + Fluorouracil,CET-CF, Cetuximab + Cisplatin + Fluorouracil,N-CF, Nivolumab + Cisplatin + Fluorouracil,Nim-CF, Nimotuzumab + Cisplatin + Fluorouracil,Ser-CF, Serplulimab + Cisplatin + Fluorouracil), (C) Forest Plot.
Figure 11
Figure 11
Meta-Analysis of Anorexia. (A) Network Plot(Each circle represents a different intervention, with the size of the circle proportional to the number of people in that intervention, and the line between the circles represents the existence of a direct comparison between the two interventions, with the thickness of the line representing the proportional number of studies), (B) Area under the Cumulative Probability Curve(Surface Under the Cumulative Ranking Curve of different intervention, CF, Cisplatin + Fluorouracil; NI, Nivolumab + Ipilimumab,P-CF, Pembrolizumab + Cisplatin + Fluorouracil,N-CF, Nivolumab + Cisplatin + Fluorouracil,Nim-CF, Nimotuzumab + Cisplatin + Fluorouracil,Ser-CF, Serplulimab + Cisplatin + Fluorouracil), (C) Forest Plot.
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References

    1. Jiang Z, Wang J, Shen Z, Zhang Z, Wang S. Characterization of esophageal microbiota in patients with esophagitis and esophageal squamous cell carcinoma. Front Cell Infection Microbiol. (2021) 11. doi: 10.3389/fcimb.2021.774330 - DOI - PMC - PubMed
    1. Niu C, Liu Y, Wang J, Liu Y, Zhang S, Zhang Y, et al. . Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study. BMC Cancer. (2021) 21:1034. doi: 10.1186/s12885-021-08764-x - DOI - PMC - PubMed
    1. Uhlenhopp DJ, Then EO, Sunkara T, Gaduputi V. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. (2020) 13:1010–21. doi: 10.1007/s12328-020-01237-x - DOI - PubMed
    1. Hirano H, Kato K. Systemic treatment of advanced esophageal squamous cell carcinoma: chemotherapy, molecular-targeting therapy and immunotherapy. Jpn J Clin Oncol. (2019) 49:412–20. doi: 10.1093/jjco/hyz034 - DOI - PubMed
    1. Rogers JE, Yamashita K, Sewastjanow-Silva M, Rosa Vicentini E, Waters R, Ajani JA. Nivolumab combination therapy as first-line treatments for unresectable, advanced or metastatic esophageal squamous cell carcinoma. Expert Rev Anticancer Ther. (2023) 23:565–71. doi: 10.1080/14737140.2023.2207826 - DOI - PubMed

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