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克唑替尼一线治疗与化疗在ALK阳性肺癌中的疗效比较
First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer


Benjamin J. Solomon ... 肿瘤 呼吸系统疾病 • 2014.12.04
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• 晚期非小细胞肺癌的精确诊断和治疗 • 对阿来替尼和克唑替尼用于未经治疗的ALK阳性非小细胞肺癌的比较研究 • ASCO 2017报告——肺癌

摘要


背景

ALK阳性的晚期非小细胞肺癌(NSCLC)中,与标准化疗作为一线治疗相比,ALK小分子抑制剂克唑替尼一线治疗的疗效尚不明确。


方法

我们实施了项开放性、三期临床试验,比较克唑替尼与化疗对343例既往未接受过针对晚期肺癌的全身治疗ALK阳性的晚期非鳞状细胞的NSCLC患者的疗效。这些患者随机分为两组,分别接受克唑替尼治疗(250 mg口服,每天2次),或者接受静脉化疗(培美曲赛500 mg/m2+顺铂75 mg/m2,或卡铂,曲线下面积目标为5~6 mg/(ml·min),每3周一个疗程,共6个疗程)。对于化疗组的患者,在出现疾病进展后,我们允许他们转入到克唑替尼治疗组。本试验的主要终点是无进展生存期;我们采用影像学方法对无进展生存期进行独立的评估。


结果

克唑替尼组的无进展生存期较化疗组显著延长(中位值,10.9个月对7.0个月;克唑替尼组出现疾病进展或死亡的风险比为0.45,95%可信区间[CI]为0.35~0.60,P<0.001)。两组的客观缓解率分别为74%和45%(P<0.001)。两组的中位总生存期均未达到(克唑替尼组的死亡风险比为0.82,95% CI 0.54~1.26,P=0.36)。克唑替尼组的1年生存率为84%,化疗组为79%。克唑替尼组最常见的不良事件包括视觉障碍、腹泻、恶心以及水肿。化疗组最常见的不良事件为恶心、乏力、呕吐和食欲下降。与化疗相比,克唑替尼可以显著减轻肺癌的相关症状并大幅提高生活质量。


结论

对于ALK阳性并且此前未曾接受过治疗的晚期NSCLC,克唑替尼的疗效优于标准的一线培美曲塞+铂类联合化疗的疗效(由辉瑞公司[Pfizer]资助,PROFILE 1014在ClinicalTrials.gov注册号为NCT01154140)。





作者信息

Benjamin J. Solomon, M.B., B.S., Ph.D., Tony Mok, M.D., Dong-Wan Kim, M.D., Ph.D., Yi-Long Wu, M.D., Kazuhiko Nakagawa, M.D., Ph.D., Tarek Mekhail, M.D., Enriqueta Felip, M.D., Ph.D., Federico Cappuzzo, M.D., Jolanda Paolini, B.Sc., Tiziana Usari, B.Sc., Shrividya Iyer, Ph.D., Arlene Reisman, M.P.H., Keith D. Wilner, Ph.D., Jennifer Tursi, M.Sc., and Fiona Blackhall, M.D., Ph.D., for the PROFILE 1014 Investigators*
From Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.J.S.); State Key Laboratory of South China, Hong Kong Cancer Institute, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin (T. Mok), and Guangdong Lung Cancer Institute, Guangzhou (Y.-L.W.) — both in China; Seoul National University Hospital, Seoul, South Korea (D.-W.K.); Kinki University, Osaka, Japan (K.N.); Florida Hospital Cancer Institute, Orlando (T. Mekhail); Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona (E.F.); Istituto Toscano Tumori, Livorno (F.C.), and Pfizer Oncology, Milan (J.P., T.U., J.T.) — both in Italy; Pfizer Oncology (S.I.) and Pfizer Global Innovative Pharma Business (A.R.) — both in New York; Pfizer Oncology, La Jolla, CA (K.D.W.); and the Christie Hospital and Institute of Cancer Sciences, Manchester University, Manchester, United Kingdom (F.B.).

 

参考文献

1. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-566

2. Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007;131:1190-1203

3. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009;27:4247-4253

4. Camidge DR, Doebele RC. Treating ALK-positive lung cancer — early successes and future challenges. Nat Rev Clin Oncol 2012;9:268-277

5. Blackhall FH, Peters S, Bubendorf L, et al. Prevalence and clinical outcomes for patients with ALK-positive resected stage I-III adenocarcinoma: results from the European Thoracic Oncology Platform Lungscape Project. J Clin Oncol 2014;32:2780-2787

6. Christensen JG, Zou HY, Arango ME, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther 2007;6:3314-3322

7. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non–small-cell lung cancer. N Engl J Med 2010;363:1693-1703

8. Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol 2012;13:1011-1019

9. Kim D-W, Ahn M-J, Shi Y, et al. Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC). J Clin Oncol 2012;30:Suppl. abstract

10. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368:2385-2394

11. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non–small-cell lung cancer. N Engl J Med 2002;346:92-98

12. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26:3543-3551

13. Abbott Molecular. Vysis ALK Break Apart FISH Probe Kit package insert, 2011 (http://www.abbottmolecular.com/static/cms_workspace/pdfs/US/Vysis_ALK_FISH_Probe_Kit_PI.pdf).

14. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247

15. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-655

16. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-376

17. Fayers P, Bottomley A. Quality of life research within the EORTC-the EORTC QLQ-C30.Eur J Cancer 2002;38:Suppl 4:S125-S133

18. Bergman B, Aaronson NK, Ahmedzai S, Kaasa S, Sullivan M. The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. Eur J Cancer 1994;30A:635-642

19. EuroQol Group. EuroQol — a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208

20. Robins JM, Tsiatis A. Correcting for non-compliance in randomized trials using rank-preserving structural failure time models. Commun Stat Theory Methods 1991;20:2609-2631

21. Robins JM, Blevins D, Ritter G, Wulfsohn M. G-estimation of the effect of prophylaxis therapy for Pneumocystis carinii pneumonia on the survival of AIDS patients. Epidemiology 1992;3:319-336

22. White IR, Babiker AG, Walker S, Darbyshire JH. Randomization-based methods for correcting for treatment changes: examples from the Concorde trial. Stat Med 1999;18:2617-2634

23. Temple R. Hy’s law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf 2006;15:241-243

24. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-957

25. 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. Lancet Oncol 2012;13:239-246

26. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31:3327-3334

27. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non–small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-2388

28. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010;11:121-128

29. Camidge DR, Kono SA, Lu X, et al. Anaplastic lymphoma kinase gene rearrangements in non-small cell lung cancer are associated with prolonged progression-free survival on pemetrexed. J Thorac Oncol 2011;6:774-780

30. Shaw AT, Varghese AM, Solomon BJ, et al. Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer. Ann Oncol 2013;24:59-66

31. Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 2012;13:247-255

32. Mok T, Yang JJ, Lam KC. Treating patients with EGFR-sensitizing mutations: first line or second line — is there a difference? J Clin Oncol 2013;31:1081-1088

33. Shaw AT, Solomon BJ, Mok T, et al. Effect of treatment duration on incidence of adverse events (AEs) in a phase III study of crizotinib versus chemotherapy in advanced ALK-positive non-small cell lung cancer (NSCLC). Presented at the 15th World Conference on Lung Cancer, Sydney, October 27–30, 2013. abstract.

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