提示: 手机请竖屏浏览!

食管癌或胃食管结合部癌切除术后的纳武利尤单抗辅助治疗
Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer


Ronan J. Kelly ... 肿瘤 • 2021.04.01
相关阅读
• 晚期食管癌二线治疗中应用帕博利珠单抗与应用化疗的比较 • 帕博利珠单抗治疗难治性胃癌或胃食管结合部癌

摘要


背景

对于新辅助放化疗和手术后复发风险仍然高的食管癌或胃食管结合部癌患者,目前尚未确立辅助治疗。

 

方法

我们开展了全球性、随机、双盲、安慰剂对照3期试验CheckMate 577,该试验在食管癌或胃食管结合部癌患者中评估了检查点抑制剂辅助治疗。我们以2∶1的比例将接受过新辅助放化疗,并且仍有残留病变的切除术后(R0)Ⅱ期或Ⅲ期食管癌或胃食管结合部癌成人患者随机分组,两组分别接受纳武利尤单抗(以每2周240 mg的剂量给药16周,之后以每4周480 mg的剂量给药)或匹配安慰剂治疗。试验干预期的最长持续时间为1年。主要终点是无病生存期。

 

结果

中位随访时间为24.4个月。接受纳武利尤单抗的532例患者的中位无病生存期为22.4个月(95%置信区间[CI],16.6~34.0),而接受安慰剂的262例患者的中位无病生存期为11.0个月(95% CI,8.3~14.3)(疾病复发或死亡的风险比,0.69;96.4% CI,0.56~0.86;P<0.001)。在多个预设亚组中,纳武利尤单抗组的无病生存期均优于安慰剂组。纳武利尤单抗组532例患者中的71例(13%)和安慰剂组260例患者中的15例(6%)发生了研究者认为与活性药物或安慰剂相关的3级或4级不良事件。纳武利尤单抗组9%的患者和安慰剂组3%的患者因与活性药物或安慰剂相关的不良事件停用试验治疗方案。

 

结论

在接受过新辅助放化疗的食管癌或胃食管结合部癌切除术后患者中,接受纳武利尤单抗辅助治疗的患者的无病生存期显著超过接受安慰剂的患者(由百时美施贵宝和小野制药[Ono Pharmaceutical]资助;CheckMate 577在ClinicalTrials.gov注册号为NCT02743494)。





作者信息

Ronan J. Kelly, M.B., B.Ch., M.B.A., Jaffer A. Ajani, M.D., Jaroslaw Kuzdzal, M.D., Ph.D., Thomas Zander, M.D., Eric Van Cutsem, M.D., Ph.D., Guillaume Piessen, M.D., Ph.D., Guillermo Mendez, M.D., Josephine Feliciano, M.D., Satoru Motoyama, M.D., Ph.D., Astrid Lièvre, M.D., Ph.D., Hope Uronis, M.D., Elena Elimova, M.D., Cecile Grootscholten, M.D., Ph.D., Karen Geboes, M.D., Ph.D., Syed Zafar, M.D., Stephanie Snow, M.D., Andrew H. Ko, M.D., Kynan Feeney, M.D., Michael Schenker, M.D., Ph.D., Piotr Kocon, M.D., Ph.D., Jenny Zhang, M.D., Ph.D., Lili Zhu, Ph.D., Ming Lei, Ph.D., Prianka Singh, Pharm.D., M.P.H., Kaoru Kondo, M.Sc., James M. Cleary, M.D., Ph.D., and Markus Moehler, M.D., Ph.D. for the CheckMate 577 Investigators*
From the Charles A. Sammons Cancer Center at Baylor University Medical Center, Dallas (R.J.K.), and the University of Texas M.D. Anderson Cancer Center, Houston (J.A.A.); Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland (J.K., P.K.); the University Hospital Cologne, Department of Internal Medicine, Center for Integrated Oncology Aachen–Bonn–Cologne–Duesseldorf, Gastrointestinal Cancer Group Cologne, Cologne (T.Z.), and University Medical Center of Johannes Gutenberg–University Mainz (M.M.) — both in Germany; University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven (E.V.C.), and Ghent University Hospital, Ghent (K.G.) — both in Belgium; University Lille, Claude Huriez University Hospital, Lille (G.P.), and Pontchaillou University Hospital, Department of Gastroenterology, University of Rennes 1, INSERM Unité 1242, Rennes (A.L.) — both in France; Fundación Favaloro, Buenos Aires (G.M.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore (J.F.); Akita University Hospital, Akita, Japan (S.M.); Duke Cancer Institute, Durham, NC (H.U.); Princess Margaret Cancer Centre, Toronto (E.E.), and Queen Elizabeth II Health Sciences Centre, Halifax, NS (S.S.) — both in Canada; the Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (C.G.); Florida Cancer Specialists and Research Institute, Fort Myers (S.Z.); University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (A.H.K.); St. John of God Murdoch Hospital, Murdoch, WA, Australia (K.F.); Sfantul Nectarie Oncology Center, Craiova, Romania (M.S.); Bristol Myers Squibb, Princeton, NJ (J.Z., L.Z., M.L., P.S., K.K.); and Dana–Farber Cancer Institute, Boston (J.M.C.). Address reprint requests to Dr. Kelly at the Charles A. Sammons Cancer Center at Baylor University Medical Center, 3410 Worth St., Suite 550, Dallas, TX 75246, or at ronan.kelly@bswhealth.org. *A complete list of the CheckMate 577 sites and investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.

2. Arnold M, Ferlay J, van Berge Henegouwen MI, Soerjomataram I. Global burden of oesophageal and gastric cancer by histology and subsite in 2018. Gut 2020;69:1564-1571.

3. Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends — an update. Cancer Epidemiol Biomarkers Prev 2016;25:16-27.

4. Lordick F, Mariette C, Haustermans K, Obermannová R, Arnold D. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016;27:Suppl 5:v50-v57.

5. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: esophageal and esophagogastric junction cancers, version 2. Plymouth Meeting, PA: 2020.

6. Shah MA, Kennedy EB, Catenacci DV, et al. Treatment of locally advanced esophageal carcinoma: ASCO guideline. J Clin Oncol 2020;38:2677-2694.

7. Blum Murphy M, Xiao L, Patel VR, et al. Pathological complete response in patients with esophageal cancer after the trimodality approach: the association with baseline variables and survival — the University of Texas MD Anderson Cancer Center experience. Cancer 2017;123:4106-4113.

8. Depypere LP, Vervloet G, Lerut T, et al. ypT0N+: the unusual patient with pathological complete tumor response but with residual lymph node disease after neoadjuvant chemoradiation for esophageal cancer, what’s up? J Thorac Dis 2018;10:2771-2778.

9. Klevebro F, Nilsson K, Lindblad M, et al. Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer: a national cohort study. Dis Esophagus 2020;33(5):doz078-doz078.

10. Rice TW, Lerut TEMR, Orringer MB, et al. Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data. Dis Esophagus 2016;29:715-723.

11. Sisic L, Blank S, Nienhüser H, et al. Prognostic differences in 8th edition TNM staging of esophagogastric adenocarcinoma after neoadjuvant treatment. Eur J Surg Oncol 2018;44:1646-1656.

12. Kang Y-K, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:2461-2471.

13. Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2019;20:1506-1517.

14. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-1474.

15. Oba K, Paoletti X, Alberts S, et al. Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis. J Natl Cancer Inst 2013;105:1600-1607.

16. Lei M, Siemers N, Pandya D, et al. Association of PD-L1 combined positive score and immune gene signatures with efficacy of nivolumab (NIVO) ± ipilimumab (IPI) in patients with metastatic gastroesophageal cancer (mGEC). Cancer Res 2019;79:Suppl 13:2673-2673. abstract.

17. Garg PK, Sharma J, Jakhetiya A, Goel A, Gaur MK. Preoperative therapy in locally advanced esophageal cancer. World J Gastroenterol 2016;22:8750-8759.

18. Smyth EC, Lagergren J, Fitzgerald RC, et al. Oesophageal cancer. Nat Rev Dis Primers 2017;3:17048-17048.

19. Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017;377:1824-1835.

20. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019;393:1948-1957.

21. Janjigian YY, Bendell J, Calvo E, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol 2018;36:2836-2844.

22. Kudo T, Hamamoto Y, Kato K, et al. Nivolumab treatment for oesophageal squamous-cell carcinoma: an open-label, multicentre, phase 2 trial. Lancet Oncol 2017;18:631-639.

服务条款 | 隐私政策 | 联系我们