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. 2022 Feb 25:12:732814.
doi: 10.3389/fonc.2022.732814. eCollection 2022.

Adjuvant Therapy With PD1/PDL1 Inhibitors for Human Cancers: A Systematic Review and Meta-Analysis

Affiliations

Adjuvant Therapy With PD1/PDL1 Inhibitors for Human Cancers: A Systematic Review and Meta-Analysis

Yao Jin et al. Front Oncol. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) have made a breakthrough in the systemic treatment of patients with advanced tumors. However, little is known about their efficacy and safety in adjuvant settings after the resection of solid tumors.

Methods: We performed a meta-analysis on the efficacy and safety of programmed death 1 (PD1)/PD-1 ligand (PDL1) inhibitors in adjuvant therapy after tumor resection using Review Manager 5.3, based on published clinical studies. The outcomes included recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), and adverse events (AEs).

Results: Eight randomized controlled trials (RCTs) were included in the analysis. The use of PD1/PDL1 inhibitors in adjuvant therapy significantly improved RFS (hazard ratio [HR] = 0.72; 95% confidence interval [CI] 0.67-0.78, p < 0.00001). However, there was no statistically significant difference in OS between PD1/PDL1 inhibitors and placebo (HR = 0.86; 95% CI 0.74-1.00, p = 0.05). Gender, age, and PDL1 status were independent predictors of RFS with PD1/PDL1 inhibitors. As for the safety analysis results, PD1/PDL1 inhibitors had a higher incidence of fatigue (risk ratio [RR] = 1.22; 95% CI 1.01-1.49, p = 0.04), nausea (RR = 1.47; 95% CI 1.11-1.94, p = 0.007), and pruritus (RR = 1.96; 95% CI 1.57-2.44, p < 0.00001). In addition, the incidence of any grade adverse events increased in the PD1/PDL1 inhibitor group (RR = 1.03; 95% CI 1.02-1.05, p < 0.0001).

Conclusions: This is the first meta-analysis on the efficacy and safety of PD1/PDL1 inhibitors in adjuvant therapy. The use of PD1/PDL1 inhibitors in adjuvant therapy could significantly reduce the recurrence rate after solid tumor resection. However, the incidence of fatigue, nausea, pruritus, and any grade AEs also increased, which should be monitored with vigilance.

Keywords: PD1; PDL1; adjuvant therapy; human cancers; immune checkpoint inhibitor; meta-analysis.

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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
PRISMA flow diagram the search strategy and results.
Figure 2
Figure 2
Risk of bias assessment at the study level. (A) Risk of bias graph: review authors’ judgment about each risk of bias item presented as percentages across all included full reported studies. (B) Risk of bias summary: review authors’ judgment about each risk of bias item for each included study.
Figure 3
Figure 3
(A) Forest plots of the fixed-effects meta-analysis for the effects of PD1/PDL1 inhibitors on RFS. (B) Forest plots of the fixed-effects meta-analysis for the effects of PD1/PDL1 inhibitors on PFS in gender. (C) Forest plots of the fixed-effects meta-analysis for the effects of PD1/PDL1 inhibitors on RFS in different age group. (D) Forest plots of the fixed-effects meta-analysis for the effects of PD1/PDL1 inhibitors on RFS in different PDL1 status.
Figure 4
Figure 4
Forest plots of the fixed-effects meta-analysis for the effects of PD1/PDL1 inhibitors on OS.
Figure 5
Figure 5
The risk of any grade AEs in the PD1/PDL1 inhibitors groups and placebo groups.
Figure 6
Figure 6
The incidence of different adverse events in the PD1/PDL1 inhibitors groups and placebo groups.
Figure 7
Figure 7
(A) Funnel plot analysis of potential publication bias for RFS. (B) Funnel plot analysis of potential publication bias for OS. (C) Funnel plot analysis of potential publication bias for any advent events.

References

    1. Thomas D, Bello DM. Adjuvant Immunotherapy for Melanoma. J Surg Oncol (2021) 123(3):789–97. doi: 10.1002/jso.26329 - DOI - PubMed
    1. Watanabe SI, Nakagawa K, Suzuki K, Takamochi K, Ito H, Okami J, et al. . Neoadjuvant and Adjuvant Therapy for Stage III non-Small Cell Lung Cancer. Jpn J Clin Oncol (2017) 47(12):1112–8. doi: 10.1093/jjco/hyx147 - DOI - PubMed
    1. Agha A, Tarhini AA. Adjuvant Therapy for Melanoma. Curr Oncol Rep (2017) 19(5):36. doi: 10.1007/s11912-017-0594-5 - DOI - PubMed
    1. Testori AAE, Ribero S, Indini A, Mandalà M. Adjuvant Treatment of Melanoma: Recent Developments and Future Perspectives. Am J Clin Dermatol (2019) 20(6):817–27. doi: 10.1007/s40257-019-00456-4 - DOI - PubMed
    1. Cockrell C, Teague J, Axelrod DE. Prevention of Colon Cancer Recurrence From Minimal Residual Disease: Computer Optimized Dose Schedules of Intermittent Apoptotic Adjuvant Therapy. JCO Clin Cancer Inform (2020) 4:514–20. doi: 10.1200/CCI.20.00016 - DOI - PMC - PubMed

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