提示: 手机请竖屏浏览!

纳武利尤单抗一线治疗Ⅳ期或复发性非小细胞肺癌
First-Line Nivolumab in Stage IV or Recurrent Non–Small-Cell Lung Cancer


David P. Carbone ... 肿瘤 呼吸系统疾病 • 2017.06.22
相关阅读
• 可切除肺癌的纳武利尤单抗新辅助治疗 • 纳武利尤单抗治疗转移性高微卫星不稳定性(MSI)或DNA错配修复缺陷性(dMMR)结直肠癌 • 纳武利尤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 • 纳武利尤单抗治疗晚期肝细胞癌 • 帕博利珠单抗与化疗治疗PD-L1阳性非小细胞肺癌的比较研究 • Pembrolizumab治疗非小细胞肺癌的研究 • 抗PD-1抗体在癌症治疗中的安全性、有效性和免疫的相关性

晚期非小细胞肺癌的一线治疗:从双剑合璧到三剑客

 

刘天舒

复旦大学附属中山医院肿瘤内科

 

晚期非小细胞肺癌(NSCLC)一线方案的更新一直处于肿瘤治疗进展的最前沿。在过去的20年间,以铂类为基础的联合化疗是晚期NSCLC的一线标准治疗。随着分子靶向治疗时代的到来,有关肺癌驱动基因、精准治疗的研究不断刷新着晚期肺癌的一线治疗策略。经过近十几年的发展,针对不同驱动基因甚至耐药靶点的药物如雨后春笋般不断涌现,如一代/二代/三代EGFR-TKI1,2、ALK抑制剂3等,并陆续成为某些分子亚型晚期肺癌的一线治疗方案。这些疗法不仅改善了生存期,而且用药方式简便,极大地提高了患者的生活质量。然而,对于没有EGFRALK等基因变异的患者,除了化疗,是否还有其他更好的一线方案?

查看更多

摘要


背景

在之前接受过治疗的非小细胞肺癌(NSCLC)患者中,与多西他赛相比,纳武利尤单抗(nivolumab)治疗与更长的总生存期相关。在一项开放标签3期临床试验中,我们在程序性死亡蛋白配体-1(PD-L1)阳性的NSCLC患者中对纳武利尤单抗与化疗作为一线治疗进行了比较。

 

方法

我们按照1︰1的比例将患有未经治疗的Ⅳ期或复发性NSCLC,且PD-L1肿瘤表达水平≥1%的患者随机分配接受纳武利尤单抗治疗(每2周1次静脉给药,剂量为3 mg/kg)或铂类化疗(每3周1次给药,最多6个周期)。接受化疗的患者可以在疾病进展时跨线至纳武利尤单抗治疗。主要终点是在PD-L1表达水平≥5%的患者中,通过盲法独立集中审查评估的无进展生存期。

 

结果

在423例PD-L1表达水平≥5%的患者中,纳武利尤单抗组的中位无进展生存期为4.2个月,而化疗组为5.9个月(疾病进展或死亡的风险比,1.15;95%置信区间[CI],0.91~1.45;P=0.25),中位总生存期分别为14.4个月和13.2个月(死亡风险比,1.02;95% CI,0.80~1.30)。化疗组212例患者中共计128例(60%)接受纳武利尤单抗作为后续治疗。有71%接受纳武利尤单抗治疗和92%接受化疗的患者发生任一级别与治疗相关的不良事件。有18%接受纳武利尤单抗治疗和51%接受化疗的患者发生3级或4级与治疗相关的不良事件。

 

结论

在患有之前未经治疗,PD-L1表达水平≥5%的Ⅳ期或复发性NSCLC的患者中,纳武利尤单抗治疗组的无进展生存期未显著超过化疗组。两组的总生存期相近。与化疗相比,纳武利尤单抗治疗具有良好的安全性,没有新的或非预期的安全信号(由百时美施贵宝公司等资助;CheckMate 026在ClinicalTrials.gov注册号为NCT02041533)。





作者信息

David P. Carbone, M.D., Ph.D., Martin Reck, M.D., Ph.D., Luis Paz-Ares, M.D., Benjamin Creelan, M.D., Leora Horn, M.D., Martin Steins, M.D., Ph.D., Enriqueta Felip, M.D., Michel M. van den Heuvel, M.D., Tudor-Eliade Ciuleanu, M.D., Firas Badin, M.D., Neal Ready, M.D., T. Jeroen N. Hiltermann, M.D., Suresh Nair, M.D., Rosalyn Juergens, M.D., Ph.D., Solange Peters, M.D., Ph.D., Elisa Minenza, M.D., John M. Wrangle, M.D., Delvys Rodriguez-Abreu, M.D., Hossein Borghaei, D.O., George R. Blumenschein, Jr., M.D., Liza C. Villaruz, M.D., Libor Havel, M.D., Jana Krejci, M.D., Jesus Corral Jaime, M.D., Han Chang, Ph.D., William J. Geese, Ph.D., Prabhu Bhagavatheeswaran, Ph.D., Allen C. Chen, M.D., and Mark A. Socinski, M.D., for the CheckMate 026 Investigators*
From the Ohio State University Comprehensive Cancer Center, Columbus (D.P.C.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf (M.R.), and Thoraxklinik, Heidelberg University Hospital, Heidelberg (M.S.) — both in Germany; Hospital Universitario Doce de Octubre, Centro Nacional de Investigaciones Oncológicas and Universidad Complutense, Madrid (L.P.-A., J.C.J.), Vall d’Hebron University Hospital, Barcelona (E.F.), and Hospital Universitario Insular de Gran Canaria, Las Palmas (D.R.-A.) — all in Spain; H. Lee Moffitt Cancer Center, Tampa, FL (B.C.); Vanderbilt University Medical Center, Nashville (L. Horn); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (M.M.H.), and University of Groningen, Universitair Medisch Centrum Groningen, Groningen (T.J.N.H.) — both in the Netherlands; Prof. Dr. Ion Chiricuta Institute of Oncology and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Baptist Health Lexington, Lexington, KY (F.B.); Duke University, Durham, NC (N.R.); Lehigh Valley Health Network, Allentown (S.N.), Fox Chase Cancer Center, Philadelphia (H.B.), and University of Pittsburgh Medical Center Cancer Center, Pittsburgh (L.C.V., M.A.S.) — all in Pennsylvania; Juravinski Cancer Centre, Hamilton, ON, Canada (R.J.); Oncology Department, Lausanne University Hospital, Lausanne, Switzerland (S.P.); Santa Maria Hospital, Terni, Italy (E.M.); Hollings Cancer Center, Charleston, SC (J.M.W.); Department of Thoracic–Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.R.B.); Klinika Pneumologie a Hrudní Chirurgie, Nemocnice Na Bulovce, Prague, Czech Republic (L. Havel, J.K.); and Bristol-Myers Squibb, Princeton, NJ (H.C., W.J.G., P.B., A.C.C.).Address reprint requests to Dr. Carbone at 488 Biomedical Research Tower, 460 W. 12th Ave., Columbus, OH 43210, or at david.carbone@osumc.edu. *A complete list of the CheckMate 026 investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Ettinger DS, Wood DE, Akerley W, et al. NCCN guidelines insights: non-small cell lung cancer, version 4.2016. J Natl Compr Canc Netw 2016;14:255-264

2. Masters GA, Temin S, Azzoli CG, et al. Systemic therapy for stage IV non–small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2015;33:3488-3515

3. 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

4. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 2012;30:2055-2062

5. Patel JD, Socinski MA, Garon EB, et al. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol 2013;31:4349-4357

6. Paz-Ares L, Mezger J, Ciuleanu TE, et al. Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study. Lancet Oncol 2015;16:328-337

7. Thatcher N, Hirsch FR, Luft AV, et al. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol 2015;16:763-774

8. Zinner RG, Obasaju CK, Spigel DR, et al. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients with advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol 2015;10:134-142

9. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N Engl J Med 2015;373:123-135

10. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med 2015;373:1627-1639

11. Barlesi F, Steins M, Horn L, et al. Long-term outcomes with nivolumab (Nivo) vs docetaxel (Doc) in patients (Pts) with advanced (Adv) NSCLC: CheckMate 017 and CheckMate 057 2-y update. Ann Oncol 2016;27:Suppl 6:215PD-215PD. abstract.

12. Gettinger S, Rizvi NA, Chow LQ, et al. Nivolumab monotherapy for first-line treatment of advanced non–small-cell lung cancer. J Clin Oncol 2016;34:2980-2987

13. Gettinger S, Shepherd FA, Antonia SJ, et al. First-line nivolumab (anti-PD-1; BMS-936558, ONO-4538) monotherapy in advanced NSCLC: safety, efficacy, and correlation of outcomes with PD-L1 status. Presented at the American Society of Clinical Oncology Annual Meeting, Chicago, June 3–7, 2014 (poster).

14. 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

15. 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

16. Wakelee HA, Wang W, Schiller JH, et al. Survival differences by sex for patients with advanced non-small cell lung cancer on Eastern Cooperative Oncology Group trial 1594. J Thorac Oncol 2006;1:441-446

17. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med 2016;375:1823-1833

18. Remon J, Besse B, Soria JC. Successes and failures: what did we learn from recent first-line treatment immunotherapy trials in non-small cell lung cancer? BMC Med 2017;15:55-55

19. Hellmann M. Mutation burden, neoantigens, and response to T cell checkpoint blockade. Presented at the 14th International Congress on Targeted Anticancer Therapies, Washington, DC, March 21–23, 2016.

20. Kowanetz M, Zou W, Shames D, et al. Tumor mutation burden (TMB) is associated with improved efficacy of atezolizumab in 1L and 2L+ NSCLC patients. J Thorac Oncol 2017;12:Suppl:S321-S321. abstract.

服务条款 | 隐私政策 | 联系我们