Racial/ethnic differences in survival and treatment response with PD-1/PD-L1 inhibitors in resectable non-small cell lung cancer: a meta-analysis of randomized controlled trials.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY European Journal of Clinical Pharmacology Pub Date : 2024-11-14 DOI:10.1007/s00228-024-03777-4

Francisco Cezar Aquino de Moraes, Eric Pasqualotto, Anna Luíza Soares de Oliveira Rodrigues, Rommel Mario Rodríguez Burbano

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Abstract

Background: The optimal treatment for resectable Non-Small Cell Lung Cancer (NSCLC) remains under investigation, particularly about its effectiveness across different ethnicities. This meta-analysis aims to investigate the potential benefits of adding PD1/PD-L1 inhibitors for treatment, stratified by ethnicity.

Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) that investigated the use of PD1/PD-L1 inhibitors to treat patients with resectable NSCLC. The outcomes evaluated were disease-free survival/event-free survival (DFS/EFS), major pathological response (MPR), and pathological complete response (pCR). Hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs) were computed for all endpoints using DerSimonian and Laird random-effects models. Statistical analyses were performed with R Software, version 4.2.3.

Results: A total of six RCTs comprising 3,827 patients with NSCLC were included. In populations of Asian descent, PD1/PD-L1 significantly improved DFS/EFS (HR 0.59; 95% CI 0.44-0.78), MPR (RR 5.76; 95% CI 3.58-9.28), and pCR (RR 25.00; 95% CI 6.17-101.36). Similarly, patients of European ancestry experienced significantly improved DFS/EFS (HR 0.77; 95% CI 0.65-0.90), MPR (RR 2.75; 95% CI 2.00-3.77), and pCR (RR 4.53; 95% CI 2.69-7.6) with PD1/PD-L1 therapy. Notably, patients with mixed ethnicity also demonstrated significant improvement in MPR (RR 4.05; 95% CI 2.60-6.33) and pCR (RR 8.44; 95% CI 3.75-19.00) when receiving PD1/PD-L1 inhibitors.

Conclusion: This comprehensive meta-analysis suggests that incorporating PD1/PD-L1 inhibitors into treatments offers a promising benefit for patients with resectable NSCLC, regardless of ethnicity. Future studies with in-depth molecular characterization of patients can further refine these findings and potentially guide the development of personalized treatment strategies based on individual ethnic backgrounds.

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PD-1/PD-L1抑制剂治疗可切除非小细胞肺癌的生存率和治疗反应的种族/人种差异：随机对照试验荟萃分析。

背景：可切除非小细胞肺癌（NSCLC）的最佳治疗方法仍在研究中，尤其是不同种族的治疗效果。本荟萃分析旨在研究在治疗中添加 PD1/PD-L1 抑制剂的潜在益处，并按种族进行分层：我们在 PubMed、Embase 和 Cochrane 数据库中检索了研究使用 PD1/PD-L1 抑制剂治疗可切除 NSCLC 患者的随机对照试验 (RCT)。评估的结果包括无病生存期/无事件生存期（DFS/EFS）、主要病理反应（MPR）和病理完全反应（pCR）。采用DerSimonian和Laird随机效应模型计算所有终点的危险比（HRs）或风险比（RRs）及95%置信区间（CIs）。统计分析使用 4.2.3 版 R 软件进行：共纳入了6项RCT研究，包括3827名NSCLC患者。在亚裔人群中，PD1/PD-L1能显著改善DFS/EFS（HR 0.59；95% CI 0.44-0.78）、MPR（RR 5.76；95% CI 3.58-9.28）和pCR（RR 25.00；95% CI 6.17-101.36）。同样，欧洲血统患者在接受PD1/PD-L1治疗后，DFS/EFS（HR 0.77；95% CI 0.65-0.90）、MPR（RR 2.75；95% CI 2.00-3.77）和pCR（RR 4.53；95% CI 2.69-7.6）均有明显改善。值得注意的是，混合种族患者在接受PD1/PD-L1抑制剂治疗后，MPR（RR 4.05；95% CI 2.60-6.33）和pCR（RR 8.44；95% CI 3.75-19.00）也有显著改善：这项综合荟萃分析表明，将PD1/PD-L1抑制剂纳入治疗可为可切除的NSCLC患者带来希望，无论患者属于哪个种族。未来对患者进行深入分子特征描述的研究可进一步完善这些发现，并有可能指导基于个体种族背景的个性化治疗策略的开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.