纳武利尤单抗辅助治疗食管或胃食管结合部癌。

Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.

机构信息

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.).

出版信息

N Engl J Med. 2021 Apr 1;384(13):1191-1203. doi: 10.1056/NEJMoa2032125.

DOI:10.1056/NEJMoa2032125

PMID:33789008

Abstract

BACKGROUND

No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer.

METHODS

We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival.

RESULTS

The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group.

CONCLUSIONS

Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).

摘要

背景

对于接受新辅助放化疗和手术治疗后仍存在高复发风险的食管或胃食管交界处癌患者，目前尚无辅助治疗方法。

方法

我们开展了 CheckMate 577 全球、随机、双盲、安慰剂对照 3 期临床试验，以评估一种检查点抑制剂作为食管或胃食管交界处癌患者的辅助治疗药物。接受过新辅助放化疗且残留病理疾病的 R0 期 II 或 III 期食管或胃食管交界处癌患者，按 2:1 的比例随机分配接受纳武利尤单抗（每 2 周 240mg，16 周后纳武利尤单抗剂量为 480mg，每 4 周 1 次）或匹配安慰剂治疗。试验干预的最长持续时间为 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。在接受纳武利尤单抗治疗的 532 例患者中，中位无病生存期为 22.4 个月（95%置信区间 [CI]，16.6 至 34.0），而接受安慰剂治疗的 262 例患者中为 11.0 个月（95%CI，8.3 至 14.3）（疾病复发或死亡的风险比，0.69；96.4%CI，0.56 至 0.86；P<0.001）。在多个预设亚组中，无病生存期均有利于纳武利尤单抗。研究者认为与活性药物或安慰剂相关的 3 级或 4 级不良事件在纳武利尤单抗组的 532 例患者中发生 71 例（13%），在安慰剂组的 260 例患者中发生 15 例（6%）。由于与活性药物或安慰剂相关的不良事件，纳武利尤单抗组有 9%的患者和安慰剂组有 3%的患者停止了试验方案。