Clinical Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer Patients with Liver Metastases: A Network Meta-Analysis of Nine Randomized Controlled Trials

Yin, Qian; Dai, Longguo; Sun, Ruizhu; Peng, Ke; Liu, Liya; Jiang, Bo

doi:10.4143/crt.2021.764

Cited by 6 publications

(8 citation statements)

References 69 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Until now, there has been insufficient evidence to determine which PD-1 or PD-L1 inhibitors are more appropriate for lung cancer patients with liver metastases. In a recent network meta-analysis of nine RCTs ( 56 ), pembrolizumab plus chemotherapy and atezolizumab plus bevacizumab plus chemotherapy provided the most benefit in the treatment of NSCLC patients with liver metastases, in terms of both OS and PFS. Based on these results, large head-to-head trials should be conducted to find the optimal regimen for this type of patient.…”

Section: Discussionmentioning

confidence: 99%

Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis

Xia

Zhang²,

Zhang³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundLiver metastasis is the most common type of lung cancer metastasis, and is a significant prognostic factor in lung cancer. However, the effect of liver metastases on the efficacy of immune checkpoint inhibitors (ICIs) remains inconsistent and controversial. The aim of this study was to explore the relationship between liver metastases and ICI efficacy in patients with advanced lung cancer based on data from randomized controlled trials (RCTs) and observational studies.MethodsPubMed, EMBASE, Cochrane Library databases, conference proceedings, as well as grey literature websites were searched for eligible studies without language restrict ion. Study quality was assessed using Cochrane tools and the Newcastle–Ottawa Quality Assessment Scale (NOS). Outcomes of interest were overall survival (OS) and progression-free survival (PFS). The difference in efficacy between patients with and without liver metastases was calculated by pooling ratios of hazard ratios (HR), as calculated using the deft approach.ResultsA total of 16 RCTs and 14 observational trials were included. Analyses of RCTs revealed a survival benefit for ICI treatment (i.e., ICI monotherapy, ICI + Chemotherapy, dual ICI therapy and dual ICI + Chemotherapy) versus standard therapies among non-small cell lung cancer (NSCLC) patients with liver metastases (PFS HR, 0.77; 95%CI, 0.61–0.97; OS HR, 0.78; 95%CI, 0.68–0.90). NSCLC patients with liver metastases achieved less PFS benefit and comparable OS benefit from ICI treatment compared with those without liver metastases (ratios of PFS–HRs, 1.19; 95%CI, 1.02–1.39; P=0.029; Ratios of OS–HRs, 1.10; 95%CI, 0.94–1.29; P=0.24). For patients with small cell lung cancer (SCLC), ICI treatment achieved a marginal effect on patients with liver metastases as compared with standard therapies (OS HR, 0.94; 95%CI, 0.73–1.23). SCLC patients with liver metastases benefited less from ICI treatment than patients without liver metastases (ratio of OS–HRs, 1.22; 95%CI, 1.01–1.46; P=0.036). In real-world data analysis, liver metastasis could be used as an independent prognostic risk factor, increasing the risk of death by 21% in lung cancer patients receiving ICI treatment compared with those without liver metastases (OS HR, 1.21; 95%CI, 1.17–1.27; P<0.0001). Subgroup analysis confirmed that this association was not modified by race (Asian vs. Western) or number of treatment lines.ConclusionsThe presence of liver metastases does not significantly influence the OS benefit of ICIs in patients with NSCLC. However, a small amount of data shows that liver metastasis restrains the magnitude of OS benefit in patients with SCLC. Liver metastasis has potential as an independent prognostic risk factor for lung cancer patients receiving ICI treatment in clinical practice.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022306449).

show abstract

Section: Discussionmentioning

confidence: 99%

Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis

Xia

Zhang²,

Zhang³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…In another meta-analysis, the authors compared the efficacy of different immunotherapy agents in advanced NSCLC patients with liver metastasis, and found that the efficacy of ICIs depends on the combination strategy. 40 Pembrolizumab plus chemotherapy, and atezolizumab plus bevacizumab plus chemotherapy were superior to other regimens for liver metastasis patients. 40 These are consistent with our findings, again suggesting that treatment combination options are one of the factors affecting the efficacy of immunotherapy.…”

Section: Discussionmentioning

confidence: 94%

“… 40 Pembrolizumab plus chemotherapy, and atezolizumab plus bevacizumab plus chemotherapy were superior to other regimens for liver metastasis patients. 40 These are consistent with our findings, again suggesting that treatment combination options are one of the factors affecting the efficacy of immunotherapy. Additional studies 41 , 42 also assessed the relationship between liver metastasis and efficacy of immunotherapy.…”

Section: Discussionmentioning

confidence: 94%

Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis

Ming

Zhao

et al. 2023

Integr Cancer Ther

View full text Add to dashboard Cite

Objective: It is not well determined whether liver metastasis is a prognostic factor for survival of metastatic non-small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitors (ICIs). We compared the efficacy of ICIs in patients with NSCLC with or without liver metastases, aiming to evaluate the impact of liver metastasis on survival of NSCLC. Methods: We systematically searched Pubmed, Embase, and the Cochrane library databases for randomized controlled trials (RCTs) on the efficacy of ICIs in the treatment of NSCLC patients with or without liver metastases. The duration of this search was from January 1, 2000 to June 1, 2022. The reviewers screened the literature, extracted data and conducted quality assessment, and used RevMan 5.4 software and Stata 14 to perform analyses. Results: A total of 17 RCTs were included, published from 2019 to 2022. For NSCLC patients with liver metastases, the risk of disease progression decreased by 36% (HR = 0.64; 95% CI: 0.55-0.75; P < .01) when treated with ICIs, and the death risk (HR = 0.82; 95% CI: 0.72-0.94; P < .01) was also reduced after ICIs treatment. For those without liver metastases, they had significantly improved PFS (HR = 0.56; 95% CI: 0.52-0.60; P < .01) and OS (HR = 0.73; 95% CI: 0.67-0.80; P < .01), compared to those of the control group. Subgroup analysis of OS in liver metastases patients suggested that OS benefit was associated with treatment strategy (for anti-PD-L1 plus chemotherapy versus chemotherapy, HR=1.04; 95% CI: 0.81-1.34; P =.75). Conclusion: For NSCLC patients with or without liver metastases, ICIs administration could improve both PFS and OS, especially for those without liver metastases. More RCTs are essential to verify these findings.

show abstract

“…[86] Moreover, a network meta-analysis of 1141 patients with NSCLC and LMs showed that atezolizumab combined with bevacizumab plus chemotherapy, and pembrolizumab combined with chemotherapy resulted in superior PFS compared with other immunotherapy, chemotherapy, or anti-angiogenic treatments. [87] In the KEYNOTE-189 study (NCT02578680), patients with advanced nonsquamous NSCLC and LMs received combined chemoimmunotherapy (n = 66, active arm) or standard chemotherapy (n = 49, control arm). [88] Firstline pembrolizumab combined with pemetrexed exhibited a signi cant increase in PFS (9.0 months vs. 4.9 months, HR: 0.48, 95% CI: 0.40-0.58) and OS (22.0 months vs. 10.7 months, HR: 0.56, 95% CI: 0.45-0.70) in metastatic nonsquamous NSCLC, regardless of the LM status, with manageable safety and tolerability.…”

Section: Immunotherapy In Combination With Chemotherapymentioning

confidence: 99%

Section: Prospective Preclinical and Clinical Strategies For Targetin...mentioning

confidence: 99%

Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer

Zhu,

Yu,

Tang

et al. 2024

Chinese Medical Journal

View full text Add to dashboard Cite

Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we review the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.

show abstract

Clinical Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer Patients with Liver Metastases: A Network Meta-Analysis of Nine Randomized Controlled Trials

Cited by 6 publications

References 69 publications

Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis

Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis

Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis

Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer

Contact Info

Product

Resources

About