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纳武单抗和多西他赛治疗晚期鳞状细胞非小细胞肺癌的比较研究
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer


Julie Brahmer ... 肿瘤 呼吸系统疾病 • 2015.07.09
相关阅读
• 晚期非小细胞肺癌的精确诊断和治疗 • 纳武单抗一线治疗Ⅳ期或复发性非小细胞肺癌

摘要


背景

在一线化疗期间或之后出现疾病进展,晚期鳞状细胞非小细胞肺癌(NSCLC)患者可选择的治疗方案有限。纳武单抗是一个全人源化IgG4、程序性死亡1(PD-1)免疫检查点抑制剂抗体。此项研究是一项随机、开放、国际性的三期临床试验,在上述患者群体中,以多西他赛为对照,评估了纳武单抗的疗效与安全性。


方法

我们将272例患者随机分配至纳武单抗与多西他赛组;纳武单抗的给药剂量为3 mg/kg体重,每2周给药1次;多西他赛的给药剂量为75 mg/m2体表面积,每3周给药1次。主要终点为总生存期。


结果

纳武单抗组的中位总生存期为9.2个月(95% 可信区间[CI], 7.3~13.3),多西他赛组为6.0个月(95% CI, 5.1~7.3)。纳武单抗组的死亡风险比多西他赛低41%(风险比0.59;95% CI,0.44~0.79;P < 0.001)。纳武单抗组的一年总生存率为42%(95% CI,34~50),多西他赛组为24%(95% CI,17~31)。纳武单抗组的有效率为20%,多西他赛组为9%(P = 0.008)。纳武单抗组的中位无进展生存期为3.5个月,多西他赛组为2.8个月(死亡或疾病进展的风险比,0.62;95% CI,0.47~0.81;P < 0.001)。PD-1配体(PD-L1)的表达水平既没有预后价值,也没有预测价值。纳武单抗组有7%的患者报告出现3级或4级治疗相关的不良事件;而多西他赛组是55%。


结论

和多西他赛相比,对曾接受过治疗的晚期鳞状细胞NSCLC患者,无论PD-L1的表达水平如何,接受纳武单抗治疗有更好的总生存期、有效率以及无进展生存期(由百时美施贵宝公司[Bristol-Myers Squibb]资助;CheckMate 017在ClinicalTrials.gov注册号为NCT01642004)。





作者信息

Julie Brahmer, M.D., Karen L. Reckamp, M.D., Paul Baas, M.D., Lucio Crinò, M.D., Wilfried E.E. Eberhardt, M.D., Elena Poddubskaya, M.D., Scott Antonia, M.D., Ph.D., Adam Pluzanski, M.D., Ph.D., Everett E. Vokes, M.D., Esther Holgado, M.D., Ph.D., David Waterhouse, M.D., Neal Ready, M.D., Justin Gainor, M.D., Osvaldo Arén Frontera, M.D., Libor Havel, M.D., Martin Steins, M.D., Marina C. Garassino, M.D., Joachim G. Aerts, M.D., Manuel Domine, M.D., Luis Paz-Ares, M.D., Martin Reck, M.D., Christine Baudelet, Ph.D., Christopher T. Harbison, Ph.D., Brian Lestini, M.D., Ph.D., and David R. Spigel, M.D.
The authors’ affiliations are listed in the Appendix. Address reprint requests to Dr. Brahmer at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Bldg., 1650 Orleans St., Rm. G94, Baltimore, MD 21287, or at brahmju@jhmi.edu.

 

参考文献

1. Travis WD. Pathology of lung cancer. Clin Chest Med 2011;32:669-692

2. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens: the TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000;18:2354-2362

3. Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000;18:2095-2103

4. Taxotere (docetaxel) U.S. prescribing information. Bridgewater, NJ: Sanofi-Aventis, May 2010. (http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020449s059lbl.pdf).

5. National Comprehensive Cancer Network (NCCN). Non-small cell lung cancer guidelines, v4. 2015 (http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#nscl).

6. Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008;372:1809-1818

7. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004;22:1589-1597

8. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-264

9. Chen YB, Mu CY, Huang JA. Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Tumori 2012;98:751-755

10. Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest 2014;94:107-116

11. Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28:3167-3175

12. Wang C, Thudium KB, Han M, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res 2014;2:846-856

13. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443-2454

14. Gettinger SN, Horn L, Gandhi L, et al. Overall survival and long-term safety of nivolumab (anti-PD-1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol2015April20 (Epub ahead of print)

15. Rizvi NA, Mazières J, Planchard D, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial Lancet Oncol 2015;16:257-265

16. 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

17. Penrod JR, Korytowsky B, Petrilla A, et al. Survival of U.S. Medicare patients with advanced non small cell lung cancer by line of therapy. J Clin Oncol 2014;32:15 Suppl. abstract

18. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 2014;384:665-673

19. Cyramza (ramucirumab) U.S. prescribing information. Indianapolis: Eli Lilly, December 2014 (http://pi.lilly.com/us/cyramza-pi.pdf).

20. FDA expands approved use of Opdivo to treat lung cancer. Press release of the Food and Drug Administration, Bethesda, MD, March 4, 2015 (http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm436534.htm).

21. Garon EB, Gandhi L, Rizvi N, et al. Antitumor activity of pembrolizumab (Pembro; MK-3475) and correlation with programmed death ligand 1 (PD-L1) expression in a pooled analysis of patients (pts) with advanced non-small cell lung carcinoma (NSCLC). Ann Oncol 2014;25:Suppl 5. abstract

22. Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014;515:563-567

23. Soria JC, Cruz C, Bahleda R, et al. Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1). Eur J Cancer 2013;49:Suppl 2. abstract

24. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124-128

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