Current status of real world study for advanced non-small cell lung cancer

doi:10.12114/j.issn.1007-9572.2020.00.350

Abstract

Abstract: Lung cancer is the malignant tumor with the highest morbidity and mortality，of which non-small cell lung cancer accounts for 80%-85%.Current clinical research on drugs for non-small cell lung cancer is in full swing.Drugs whose effectiveness has been evaluated by randomized controlled trials，the gold standard，still have limitations in clinical use，and their effectiveness can not reach the most "ideal" level in clinical practice generally.In recent years，evidence from real world practice has gradually been adopted by medical products administrative agencies.The purpose of this paper was to explore the differences between the real world study and randomized controlled trials regarding the treatment of advanced non-small cell lung cancer，and put forward relevant suggestions for real world study，so as to provide a reference for clinical evidence-based study of lung cancer.

Key words: Carcinoma, non-small-cell lung；Real world study；Randomized controlled trial；Comparative analysis

摘要： 肺癌是发病率及死亡率最高的恶性肿瘤，其中非小细胞肺癌占80%~85%，所以针对非小细胞肺癌治疗药物的临床研究开展得如火如荼。随机对照试验被认为是评价药物有效性的金标准，但也存在一定的局限性，其应用于实际临床时，常无法达到最“理想”的效果。近年来，基于真实诊疗环境下的真实世界证据逐渐被药品监管机构采纳。本文旨在探究晚期非小细胞肺癌真实世界研究与临床随机对照试验研究的差异，并对晚期非小细胞肺癌真实世界研究提出相关建议，以期为肺癌临床循证研究提供参考依据。

关键词: 癌, 非小细胞肺；真实世界研究；随机对照试验；对比分析

ZHANG Yushuang,LI Jing. Current status of real world study for advanced non-small cell lung cancer[J]. Chinese General Practice, 2020, 23(21): 2607-2614. DOI: 10.12114/j.issn.1007-9572.2020.00.350.
张玉双,李晶. 晚期非小细胞肺癌真实世界研究现状[J]. 中国全科医学, 2020, 23(21): 2607-2614. DOI: 10.12114/j.issn.1007-9572.2020.00.350.

References

［1］CHEN W Q，ZHENG R S，BAADE P D，et al．Cancer statistics in China，2015［J］．CA：A Cancer J Clin，2016，66（2）：115-132．DOI：10.3322/caac.21338. ［2］SIEGEL R L，MILLER K D，JEMAL A.Cancer statistics，2018［J］．CA Cancer J Clin，2018，68（1）：7-30．DOI：10.3322/caac.21442. ［3］VIJAYVERGIA N，MEHRA R.Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer［J］．Cancer Chemother Pharmacol，2014，74（3）：437-446．DOI：10.1007/s00280-014-2517-6. ［4］YOUNT K W，TURRENTINE F E，LAU C L，et al．Putting the value framework to work in surgery［J］．J Am Coll Surg，2015，220（4）：596-604．DOI：10.1016/j.jamcollsurg.2014.12.037. ［5］关于印发原发性肺癌等18个肿瘤诊疗规范（2018年版）的通知［EB/OL］．（2018-12-13）［2020-01-22］．http：//www.nhc.gov.cn/xxgk/pages/viewdocument.jsp?dispatchDate=&staticUrl=/yzygj/s7659/201812/b21802b199814ab7b1219b87de0cae51.shtml&wenhao=%E5%9B%BD%E5%8D%AB%E5%8A%9E%E5%8C%BB%E5%87%BD%E3%80%942018%E3%80%951125%E5%8F%B7&utitle=%E5%85%B3%E4%BA%8E%E5%8D%B0%E5%8F%91%E5%8E%9F%E5%8F%91%E6%80%A7%E8%82%BA%E7%99%8C%E7%AD%8918%E4%B8%AA%E8%82%BF%E7%98%A4%E8%AF%8A%E7%96%97%E8%A7%84%E8%8C%83%EF%BC%882018%E5%B9%B4%E7%89%88%EF%BC%89%E7%9A%84%E9%80%9A%E7%9F%A5&topictype=&topic=&publishedOrg=%E5%8C%BB%E6%94%BF%E5%8C%BB%E7%AE%A1%E5%B1%80&indexNum=000013610/2018-00328&manuscriptId=b21802b199814ab7b1219b87de0cae51. ［6］SCHILLER J H，HARRINGTON D，BELANI C P，et al．Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer［J］．N Engl J Med，2002，346（2）：92-98．DOI：10.1056/NEJMoa011954. ［7］KERBEL R S.Tumor angiogenesis［J］．N Engl J Med，2008，358（19）：2039-2049．DOI：10.1056/NEJMra0706596. ［8］YANG C H，SIMMS L，PARK K，et al．Efficacy and safety of cisplatin/pemetrexed versus cisplatin/gemcitabine as first-line treatment in East Asian patients with advanced non-small cell lung cancer：results of an exploratory subgroup analysis of a phase Ⅲ trial［J］．J Thorac Oncol，2010，5（5）：688-695．DOI：10.1097/JTO.0b013e3181d1273d. ［9］SANDLER A，GRAY R，PERRY M C，et al．Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer［J］．N Engl J Med，2006，355（24）：2542-2550．DOI：10.1056/nejmoa061884. ［10］ZHOU C C，WU Y L，CHEN G Y，et al．BEYOND：a randomized，double-blind，placebo-controlled，multicenter，phase Ⅲ study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer［J］．J Clin Oncol，2015，33（19）：2197-2204．DOI：10.1200/JCO.2014.59.4424. ［11］颜彬桔.培美曲塞一线治疗晚期非鳞非小细胞肺癌有效性及安全性的真实世界研究［D］．衡阳：南华大学，2018. YAN B J.A real-world study of pemetrexed in first-line treatment of advanced non-squamous non-small cell lung cancer on the efficacy and safety［D］．Hengyang：University of South China，2018. ［12］XING P Y，MU Y X，WANG Y，et al．Real world study of regimen containing bevacizumab as first-line therapy in Chinese patients with advanced non-small cell lung cancer［J］．Thorac Cancer，2018，9（7）：805-813．DOI：10.1111/1759-7714.12650. ［13］ZIMMERMANN S，DZIADZIUSZKO R，PETERS S.Indications and limitations of chemotherapy and targeted agents in non-small cell lung cancer brain metastases［J］．Cancer Treat Rev，2014，40（6）：716-722．DOI：10.1016/j.ctrv.2014.03.005. ［14］WILHELM I，MOLNáR J，FAZAKAS C，et al．Role of the blood-brain barrier in the formation of brain metastases［J］．Int J Mol Sci，2013，14（1）：1383-1411．DOI：10.3390/ijms14011383. ［15］PAZ-ARES L G，DE MARINIS F，DEDIU M，et al．PARAMOUNT：final overall survival results of the phase Ⅲ study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer［J］．J Clin Oncol，2013，31（23）：2895-2902．DOI：10.1200/JCO.2012.47.1102. ［16］RITTMEYER A，GORBUNOVA V，VIKSTR?M A，et al．Health-related quality of life in patients with advanced nonsquamous non-small-cell lung cancer receiving bevacizumab or bevacizumab-plus-pemetrexed maintenance therapy in AVAPERL（MO22089）［J］．J Thorac Oncol，2013，8（11）：1409-1416．DOI：10.1097/JTO.0b013e3182a46bcf. ［17］SETO T，AZUMA K，YAMANAKA T，et al．Randomized phase Ⅲ study of continuation maintenance bevacizumab with or without pemetrexed in advanced nonsquamous non-small-cell lung cancer：COMPASS（WJOG5610L）［J］．J Clin Oncol，2020，38（8）：793-803．DOI：10.1200/JCO.19.01494. ［18］QIN Y，JIANG L，LI Y，et al．PD-L1 expression affect the efficacy of pemetrexed maintenance therapy in real-world patients with advanced non-squamous NSCLC［J］．Ann Oncol，2019，30（Suppl 2）：ii60．DOI：10.1093/annonc/mdz063.062. ［19］MOK T S，WU Y L，THONGPRASERT S，et al．Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma［J］．N Engl J Med，2009，361（10）：947-957．DOI：10.1056/nejmoa0810699. ［20］ROSELL R，CARCERENY E，GERVAIS R，et al．Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer（EURTAC）：a multicentre，open-label，randomised phase 3 trial［J］．Lancet Oncol，2012，13（3）：239-246．DOI：10.1016/S1470-2045（11）70393-X. ［21］WU Y L，ZHOU C C，HU C P，et al．Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations（LUX-Lung 6）：an open-label，randomised phase 3 trial［J］．Lancet Oncol，2014，15（2）：213-222．DOI：10.1016/S1470-2045（13）70604-1. ［22］SOLOMON B J，MOK T，KIM D W，et al．First-line crizotinib versus chemotherapy in ALK-positive lung cancer［J］．N Engl J Med，2014，371（23）：2167-2177．DOI：10.1056/NEJMoa1408440. ［23］OKAMOTO I，MORITA S，TASHIRO N，et al．Real world treatment and outcomes in EGFR mutation-positive non-small cell lung cancer：long-term follow-up of a large patient cohort［J］．Lung Cancer，2018，117：14-19．DOI：10.1016/j.lungcan.2018.01.005. ［24］DING Z Y，CHEN Y Y，HONG Y，et al．Obesity has an impact on the efficacy of EGFR-TKI in NSCLC patients harbouring EGFR mutation：a real-world study［J］．Ann Oncol，2019，30（Suppl 2）：ii49-50．DOI：10.1093/annonc/mdz063.025. ［25］LIN J J，ZHU V W，YODA S，et al．Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer［J］．J Clin Oncol，2018，36（12）：1199-1206．DOI：10.1200/JCO.2017.76.2294. ［26］WU Y L，LU S，LU Y，et al．Results of PROFILE 1029，a phase Ⅲ comparison of first-line crizotinib versus chemotherapy in east Asian patients with ALK-positive advanced non-small cell lung cancer［J］．J Thorac Oncol，2018，13（10）：1539-1548．DOI：10.1016/j.jtho.2018.06.012. ［27］ZHANG B，WANG S，XU J，et al．Clinical management of advanced lung adenocarcinoma with ALK rearrangement：real-world treatment outcomes and long-term survival［J］．Ann Oncol，2019，30（Suppl 2）：ii53-54．DOI：10.1093/annonc/mdz063.040. ［28］LYNCH T J，BONDARENKO I，LUFT A，et al．Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stageⅢB/Ⅳ non-small-cell lung cancer：results from a randomized，double-blind，multicenter phaseⅡ study［J］．J Clin Oncol，2012，30（17）：2046-2054．DOI：10.1200/JCO.2011.38.4032. ［29］GOVINDAN R，SZCZESNA A，AHN M J，et al．Phase Ⅲ trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer［J］．J Clin Oncol，2017，35（30）：3449-3457．DOI：10.1200/JCO.2016.71.7629. ［30］李慧婷，莫冉冉，宋鹏，等．非小细胞肺癌免疫检查点抑制剂治疗进展［J］．中华肺部疾病杂志：电子版，2019，12（3）：382-386. LI H T，MO R R，SONG P，et al.Progress of immunocheckpoint inhibitors for non-small cell lung cancer［J］．Chinese Journal of Lung Diseases：Electronic Edition，2019，12（3）：382-386. ［31］BRAHMER J，RECKAMP K L，BAAS P，et al．Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer［J］．N Engl J Med，2015，373（2）：123-135．DOI：10.1056/NEJMoa1504627. ［32］BORGHAEI H，PAZ-ARES L，HORN L，et al.Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer［J］．N Engl J Med，2015，373：1627-1639．DOI：10.1056/NEJMoa1507643. ［33］BRUSTUGUN O T，SPRAUTEN M，HELLAND ?.Real-world data on nivolumab treatment of non-small cell lung cancer［J］．Acta Oncol，2017，56（3）：438-440．DOI：10.1080/0284186X.2016.1253865. ［34］JUERGENS R A，MARIANO C，JOLIVET J，et al．Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort［J］．Curr Oncol，2018，25（6）：384-392．DOI：10.3747/co.25.4287. ［35］孙鑫，谭婧，王雯，等．真实世界证据助推药械评价与监管决策［J］．中国循证医学杂志，2019，19（5）：521-526. SUN X，TAN J，WANG W，et al．Using real-world evidence for drug and medical device evaluation and regulatory decisions［J］．Chinese Journal of Evidence-Based Medicine，2019，19（5）：521-526. ［36］国家药品监督管理局.国家药监局关于发布真实世界证据支持药物研发与审评的指导原则（试行）的通告（2020年第1号）［EB/OL］．（2020-01-07）［2020-02-07］．http：//www.nmpa.gov.cn/WS04/CL2138/373175.html. ［37］高培，王杨，罗剑锋，等．基于真实世界数据评价治疗结局研究的统计分析技术规范［J］．中国循证医学杂志，2019，19（7）：787-793. GAO P，WANG Y，LUO J F，et al．Technical guidance for statistical analysis to assess therapeutic outcomes using real-world data［J］．Chinese Journal of Evidence-Based Medicine，2019，19（7）：787-793. ［38］杨松，马龙腾，张菁菁.中国临床医学真实世界研究施行规范［J］．解放军医学杂志，2018，43（1）：1-6.

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