Dataset Information

Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis.

ABSTRACT: Background: Organ-specific response patterns reported in previous studies indicate different response toward immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) patients with different metastatic sites. This study aims to compare the efficacy of ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. Materials and Methods: MEDLINE, Embase, and CENTRAL were searched for studies comparing ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) among included studies was analyzed using the random effects model. Results: Eight studies consisting of 988 NSCLC patients were included, 259 with brain metastases and 729 with liver metastases. No available study with bone metastases information was identified. For patients with brain metastases, ICIs significantly improved their OS (HR, 0.57; P = 0.007). For patients with liver metastases, both OS (HR, 0.72; P = 0.006), and PFS (HR, 0.72; P = 0.004) improvements were observed in the ICI treatment arm. Subgroup analysis was conducted based on target of ICIs and treatment regimen. PD-1 inhibitors could benefit patients with liver or brain metastases on OS and PFS (brain metastases: OS, HR, 0.43; P < 0.001; liver metastases: PFS, HR, 0.52; P = 0.003; OS, HR, 0.66; P = 0.001), while PD-L1 inhibitors could not. Patients with brain metastases could only gain OS improvement from ICIs combined with chemotherapy (HR, 0.41; P = 0.001), but for patients with liver metastases, the benefit was detected using ICIs single agent (HR, 0.68; P = 0.012) or ICIs combined with chemotherapy plus anti-VEGF therapy (HR, 0.52; P = 0.005). Conclusion: ICIs could significantly improve OS in NSCLC patients with brain or liver metastases compared with conventional therapy. Patients with brain metastases could only gain OS benefit from ICIs combined with chemotherapy, while those with liver metastases obtained superior OS from ICIs single agent or ICIs combined with chemotherapy plus anti-VEGF therapy.

SUBMITTER: Yang K

PROVIDER: S-EPMC7363957 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis.

Yang Kaili K Li Jiarui J Bai Chunmei C Sun Zhao Z Zhao Lin L

Frontiers in oncology 20200709

<b>Background:</b> Organ-specific response patterns reported in previous studies indicate different response toward immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) patients with different metastatic sites. This study aims to compare the efficacy of ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. <b>Materials and Methods:</b> MEDLINE, Embase, and CENTRAL were searched for studies comparing ICIs with conventional therapy in NSCLC pat ...[more]

PMID: 32733805

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Project description:BackgroundIt remains uncertain whether smoking status can effect efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC). We performed a meta-analysis to address this issue.Patients and methodsPubMed, Embase, Cochrane Library, Web of Science, and international meetings were searched until April 1, 2021, for phase 2 and 3 randomized controlled trials (RCTs) which compared ICIs with chemotherapy (CT) and reported overall survival (OS) and/or progression-free survival (PFS) data according to smoking status. This meta-analysis was registered in INPLASY platform (#INPLASY202140025). The random-effect model was used for statistical analysis.FindingsTwenty-eight articles from 24 RCTs including 13918 patients were eligible. ICIs significantly prolonged OS than CT in smokers (hazard ratio [HR] = 0.75, 95% confidence interval [CI]: 0.69-0.81), but not in never-smokers (HR = 0.87, 95% CI: 0.74-1.04); while there was no significant treatment-smoking interaction (Pinteraction = 0.11). Significant heterogeneity was observed for both smokers (OS: I2 = 60%, P = 0.0002; PFS: I2 = 74%, P < 0.0001) and never smokers (PFS: I2 = 69%, P < 0.0001). Subgroup analyses revealed that ICIs monotherapy significantly improved OS in smokers (HR = 0.76, 95% CI: 0.69-0.85) but not in never-smokers (HR = 0.93, 95% CI: 0.77-1.12, Pinteraction = 0.07), and treatment-smoking interaction was significant in patients with PD-L1 ≥50% (HR, 0.61 vs 1.18; Pinteraction = 0.005). ICIs plus CT achieved better OS either in smokers or never-smokers (HR, 0.76 vs 0.61; Pinteraction = 0.39), while dual ICIs combination prolonged OS only in smokers but never-smokers (HR, 0.68 vs 1.02; Pinteraction = 0.02).InterpretationEither ICIs monotherapy or combination therapy was superior to CT in smokers. While ICIs monotherapy and dual ICIs combination were less effective in never-smokers, and ICIs plus CT might be the optimal selection. Nevertheless, given the limitation of the high heterogeneity of studies included, the findings need to be confirmed by future RCTs focusing on this subject.FundingNone.

Project description:ImportanceNovel intermediate end points may be useful to detect signals of early activity and prioritize new therapies to treat patients with advanced malignant neoplasms, including metastatic non-small cell lung cancer (mNSCLC).ObjectiveTo explore milestone rate, a proposed intermediate end point for immunotherapy trials.Data sourcesTrials submitted to the US Food and Drug Administration with more than 150 patients and in which the intention-to-treat population was assessed were identified.Study selectionAn initial meta-analysis identified 14 randomized clinical trials for treatment of mNSCLC with active controls submitted to the US Food and Drug Administration from January 1, 2003, through December 31, 2013. An additional 11 randomized clinical trials submitted from January 1, 2014, through December 31, 2016 were included.Data extraction and synthesisTwo investigators abstracted data and pooled data to compare trial-level milestone ratios with conventional end points.Main outcomes and measuresTrial-level milestone ratios for milestone rates were calculated for overall response rate (ORR) within 6 months, 9-month progression-free survival (PFS), 9-month overall survival (OS), and 12-month OS. A weighted linear regression model evaluated associations between milestone ratios and hazard ratios (HRs). Experimental and control arms of trials testing immunotherapy, targeted therapy, and other trials were pooled to compare Kaplan-Meier survival estimates in the 3 therapeutic classes.ResultsA total of 20 013 unique patients (65.4% male and 34.6% female; mean age, 60 [range, 18-92] years) with advanced lung cancer were identified in 25 unique trials. A moderate association was observed between 12-month OS milestone ratio and OS HR (R2 = 0.80; 95% CI, 0.63-0.91) and 9-month OS milestone ratio and OS HR (R2 = 0.67; 95% CI, 0.49-0.82). No associations were observed between 9-month PFS milestone ratio and OS HR (R2 = 0.19; 95% CI, 0.03-0.49) or 6-month ORR and OS HR (R2 = 0.05; 95% CI, 0.0001-0.31). The aggregated Kaplan-Meier analysis of immunotherapy trials vs chemotherapy revealed an OS HR of 0.69 (95% CI, 0.63-0.75) and PFS HR of 0.82 (95% CI, 0.76-0.89). Targeted therapy trials vs chemotherapy had an OS HR of 0.98 (95% CI, 0.80-1.19) and PFS HR of 0.48 (95% CI, 0.42-0.56).Conclusions and relevanceThis analysis of milestone rates suggests a moderate association between OS milestones at 12 or 9 months and OS HR but not 9-month PFS or 6-month ORR milestones and OS HR. Although OS at 12 months had the strongest association with OS HR, it may not be the optimal time for future trials, which will increasingly have immunotherapy as the control, deploy new biomarker-enrichment strategies, and likely enroll patients with longer survival. Milestone rates may be useful as a complementary tool to summarize or interpret trial results or as a secondary end point in exploratory studies.

Dataset Information

Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis.

Publications

Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis.

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