编者按：2024年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI 2024）将于当地时间2024年1月18日—20日在美国旧金山举行。已于本月17日公布了除LBA摘要外的全部内容。小编将持续为您呈现本次大会研究进展，延续精彩！本文介绍食管胃癌领域的快速口头报告专场，分享最新的学术进展。紧跟学术进展脉搏，共同探索医学领域的前沿资讯！

A randomized controlled phase III trial comparing thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer: JCOG1409 (MONET trial)

一项比较胸腔镜食管切除术和开放食管切除术治疗胸段食管癌的随机对照III期试验：JCOG1409（MONET试验）

背景

方法

结果

结论

胸腔镜食管切除术（TE）可作为临床I-III期胸段食管癌患者的标准治疗方法。

临床试验信息

UMIN000017628

First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced esophageal cancer: 5-year outcomes from the phase 3 KEYNOTE-590 study

帕博利珠单抗（pembro）联合化疗（chemo）一线治疗晚期食管癌：3期KEYNOTE-590研究的5年结果

摘要号：250

背景

方法

结果

结论

经过5年的观察期，与pbo+化疗组相比，使用pembro+化疗组显示出持久的疗效，并在未经治疗的晚期食管癌患者中没有新的安全性问题。长期结果持续支持将一线pembro+化疗组应用于晚期食管癌患者。

Nivolumab (NIVO) plus (+) chemotherapy (chemo) or ipilimumab (IPI) vs chemo as 1L treatment for advanced esophageal squamous cell carcinoma (ESCC): First comprehensive biomarker analyses from CheckMate 648

纳武利尤单抗（NIVO）加（+）化疗（chemo）或伊匹木单抗（IPI）对比化疗作为晚期食管鳞状细胞癌（ESCC）的一线（1L）治疗：CheckMate 648的首次全面生物标志物分析

摘要号：251

背景

方法

结果

结论

这些结果进一步支持了在一线（1L）食管鳞状细胞癌（ESCC）中使用NIVO+化疗组和NIVO+IPI组的临床疗效，并表明多个生物标志物亚组的OS获益增强。这些生物标志物的临床实用性应在未来的试验中得到验证。

摘要原文

（一）

A randomized controlled phase III trial comparing thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer: JCOG1409 (MONET trial).

Abstract：249

Background: 

Thoracoscopic esophagectomy (TE) as minimally invasive esophagectomy for thoracic esophageal cancer has become widely prevalent around the world over the past decade. However, results from a large-scale, multicenter randomized controlled trial that compared long-term survival as the primary endpoint between TE and conventional open transthoracic esophagectomy (OE) have not yet been demonstrated. We conducted a multicenter randomized phase III study (JCOG1409) to confirm the non-inferiority of TE to OE in terms of overall survival (OS) for thoracic esophageal cancer (UMIN000017628). 

Methods: 

Eligible patients with clinical stage I-III, excluding T4, thoracic esophageal squamous cell carcinoma were randomized to undergo either OE or TE. The primary endpoint was OS, with secondary endpoints including relapse-free survival (RFS), the proportion of patients achieving R0 resection, the proportion of patients needing conversion from TE to OE, adverse events, the proportion of patients requiring re-operation, changes in postoperative respiratory dysfunction, and postoperative quality-of-life score. Non-inferiority would be confirmed if the upper limit of the confidence interval (CI) for the hazard ratio (HR) does not exceed 1.44, the predefined non-inferiority margin. 

Results: 

We randomized 300 patients, assigning 150 to the TE group and 150 to the OE group between May 2015 and June 2022. The second planned interim analysis with 64 OS events was conducted in June 2023. Median follow-up (interquartile range) was 2.6 (1.4-4.9) years. Three-year OS was 82.0% (95% CI, 73.8%-87.8%) in the TE group, and 70.9% (61.6%-78.4%) in the OE group. The Data and Safety Monitoring Committee recommended terminating the trial and publishing the results because the non-inferiority of TE to OE in terms of OS was demonstrated after adjusting for multiplicity (HR 0.64; 98.8% CI, 0.34-1.21 [,1.44], one-sided p-value for non-inferiority = 0.000726 , 0.00616). Three-year RFS in the TE group was markedly better than that in the OE group (72.9% vs. 61.9%) with HR of 0.68 (95% CI, 0.46-1.01). R0 resection proportions were 95.3% in the TE group and 90.0% in the OE group. One patient in the TE group needed conversion from TE to OE intraoperatively. The postoperative overall morbidity was similar between the two groups, but the proportion of reoperation was 2.0% in the TE group and 4.1% in the OE group. Respiratory dysfunction proportion at 3 months after surgery were significantly lower in the TE group than in the OE group. 

Conclusions: 

TE was shown to be a standard treatment for patients with clinical stage I-III thoracic esophageal cancer. Clinical trial information: UMIN000017628. 

First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced esophageal cancer: 5-year outcomes from the phase 3 KEYNOTE-590 study.

Abstract：250

Background: 

First-line (1L) pembro + chemo significantly improved survival versus placebo (pbo) + chemo in patients (pts) with advanced esophageal cancer after a median follow-up of 22.6 mo in the randomized phase 3 KEYNOTE-590 study (NCT03189719). We report 5-yr follow-up data. 

Methods: 

Eligible pts had locally advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus (ESCC), or Siewert type I gastroesophageal junction adenocarcinoma; measurable disease per RECIST v1.1; and ECOG PS 0 or 1. Pts were randomized 1:1 to receive pembro 200 mg or pbo IV every 3 weeks for ≤35 cycles both with chemo (5-fluorouracil [≤35 cycles] and cisplatin [≤6 cycles]). Primary end points were OS in pts with ESCC and PD-L1 CPS≥10 and OS and PFS per RECIST v1.1 by investigator in all pts, pts with ESCC regardless of PD-L1, and pts in the ITT population with CPS≥10. Secondary end points included ORR and DOR per RECIST v1.1 by investigator and safety. Pt-reported outcomes will also be presented. Data cutoff was July 10, 2023. 

Results: 

Overall, 749 pts were randomized to receive pembro + chemo (n = 373) or pbo + chemo (n = 376). Median time from randomization to data cutoff was 58.8 mo (range, 49.2-70.6). A total of 701/740 pts (94.7%) discontinued treatment; most commonly due to progressive disease (n = 449; 60.7%). ORR and DOR by pt population are provided (Table). In the ITT population, median OS was 12.3 mo for pembro + chemo and 9.8 mo for pbo + chemo (HR 0.72 [95% CI 0.62-0.84]); 5-yr OS rates were 10.6% and 3.0%, respectively. Median PFS was 6.3 mo for pembro + chemo and 5.8 mo for pbo + chemo (HR 0.64 [95% CI 0.54-0.75]); 5-yr PFS rates were 5.5% and 0%, respectively. Grade 3-5 treatmentrelated AEs occurred in 266 (71.9%) pts in the pembro + chemo arm and 250 (67.6%) pts in the pbo + chemo arm. Treatment-related AEs led to death in 9 (2.4%) and 5 (1.4%) pts in the pembro + chemo and pbo + chemo arms, respectively. 

Conclusions: 

After 5 yrs, use of pembro + chemo showed durable efficacy versus pbo + chemo, with no new safety concerns in pts with untreated advanced esophageal cancer. Long-term results continue to support 1L pembro + chemo for advanced esophageal cancer. Clinical trial information: NCT03189719. 

（三）

Nivolumab (NIVO) plus (+) chemotherapy (chemo) or ipilimumab (IPI) vs chemo as 1L treatment for advanced esophageal squamous cell carcinoma (ESCC): First comprehensive biomarker analyses from CheckMate 648

Abstract：252

Background: 

NIVO + chemo and NIVO + IPI demonstrated superior overall survival (OS) vs chemo in previously untreated patients with advanced ESCC in CheckMate 648 (NCT03143153), resulting in approvals in many countries. We present first comprehensive exploratory biomarker analysis results from this trial. 

Methods: 

Whole exome sequencing (WES) of baseline tumor tissue and matching blood was performed to assess tumor mutational burden (TMB) and select gene alterations. TMB-high tumors were defined as ≥199 mutations/exome. RNA sequencing of baseline tumor tissue was used to assess gene expression signatures (GES). GES subgroups were defined by signature score tertiles. 

Results: 

In total, 60% (191/321) of patients receiving NIVO + chemo were both WES- and GES-evaluable; 62% (200/325) and 58% (188/325) of patients receiving NIVO + IPI and 59% (190/324) and 59% (192/324) receiving chemo were WES- and GES-evaluable, respectively. In the NIVO + chemo arm, patients with TMB-high tumors had numerically longer median OS (mOS) compared with TMB-low tumors, whereas mOS was similar between TMB subgroups treated with NIVO + IPI, although the number of patients with TMB-high tumors was small (Table). Higher inflammation and lower b-catenin GES scores were associated with improved OS benefit of NIVO + chemo or IPI vs chemo (Table). Lower fibroblast GES scores were associated with improved OS benefit of NIVO + IPI vs chemo (Table). Additional biomarker analyses, including select gene alterations and GES in tumor cell PD-L1 subgroups, will be presented. 

Conclusions:

These results further support the clinical efficacy of NIVO + chemo and NIVO + IPI in 1L ESCC and suggest enhanced OS benefit in multiple biomarker subgroups. The clinical utility of these biomarkers should be validated in future trials. Clinical trial information: NCT03143153.