纳武利尤单抗治疗食管癌或胃食管结合部癌

NEJM Quick Take以动画形式，在2分钟内介绍一篇最新NEJM论著。《NEJM医学前沿》每周同步更新当期NEJM论著的视频总结并配以中文字幕，让读者迅速掌握文章精髓。点击“阅读原文”，阅读对应NEJM论著。

纳武利尤单抗治疗食管癌或胃食管结合部癌

Nivolumab in Esophageal or Gastroesophageal Junction Cancer

2021年4月1日

朗读者：Dr. Stephen Morrissey, NEJM常务执行主编

食管癌每年造成50多万人死亡。对于可切除的局部晚期食管癌或胃食管结合部癌患者，新辅助放化疗联合之后的手术是广泛采用的标准治疗，但复发风险仍然较高，此外术后标准治疗是监测。短视频中总结了新的研究发现。                                    

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

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。

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.

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价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。

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.

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。

Result

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.

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。）

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.)

Ronan J. Kelly, Jaffer A. Ajani, Jaroslaw Kuzdzal, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. DOI: 10.1056/NEJMoa2032125