新辅助Nivolumab + Ipilimumab和Nivolumab辅助治疗局部错配修复缺陷/微卫星不稳定性胃或食管胃交界腺癌

SCI

3 September 2022

Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study

(J Clin Oncol; IF:50.717)

Correspondence to: Thierry Andr´ e, MD, Saint-Antoine Hospital, 184 rue du Faubourg Saint Antoine, 75012 Paris, France; 

André T, Tougeron D, Piessen G et al. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study. J Clin Oncol 2022; Jco2200686. 

PURPOSE 目的

In patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, surgery plus perioperative platinum-based chemotherapy is the standard of care. Perioperative chemotherapy remains debatable for gastric/GEJ adenocarcinoma with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H).

对于可切除的胃/胃食管交界处(GEJ)腺癌患者，手术联合围手术期铂基化疗是标准的方案。缺乏错配修复(dMMR)/微卫星不稳定性(MSI-H)胃/GEJ腺癌的围手术期化疗仍有争议。

PATIENTS AND METHODS  患者和方法

NEONIPIGA (ClinicalTrials.gov identifier: NCT04006262) phase II study evaluated neoadjuvant nivolumab 240 mg once every two weeks *6 and ipilimumab 1 mg/kg once every six weeks *2, followed by surgery and adjuvant nivolumab 480 mg once every four weeks (nine injections) in patients with locally advanced resectable dMMR/MSI-H, clinical (c) tumor (T)2-T4 node (N)x metastasis (M)0 gastric/GEJ adenocarcinoma. The primary end point was a pathological complete response (pCR) rate.

NEONIPIGA (ClinicalTrials.gov:NCT04006262) II期研究评估了局部晚期可切除dMMR/MSI-H，临床(c)肿瘤T2-T4淋巴结(N)x转移(M)0胃/GEJ腺癌患者的新辅助nivolumab 240 mg/ 2周6次和ipilimumab 1 mg/kg / 6周2次，随后手术和辅助nivolumab 480 mg/ 4周(9次)。主要终点是病理完全缓解(pCR)率。

RESULTS 结果

Between October 2019 and June 2021, 32 patients with dMMR/MSI-H gastric/GEJ adenocarcinoma were enrolled. The median age was 65.5 years (range, 40-80). Clinical stages were cT2-T3N0 (n=59), cT2-T3N1 (n=522), and cT3N1M1 (n=51, wrongly included).With amedian follow-up of 14.9months (95%CI, 10.6 to 17.6), 32 patients received neoadjuvant immunotherapy (27 patients completed all cycles). Neoadjuvant therapy-related grade 3/4 adverse events occurred in six patients (19%). Twenty-nine patients underwent surgery; three did not have surgery and had complete endoscopic response with tumor-free biopsies and a normal computed tomography scan (two refused surgery and one had metastasis at inclusion). The rate of surgical morbidity (Clavien-Dindo classification) was 55% (one postoperative death occurred). All 29 patients had anR0 resection, and 17 (58.6%; 90%CI, 41.8 to 74.1) had pCR (pathological T0N0). Becker tumor regression grades 1a, 1b, 2, and 3 were observed in 17 patients, three (including two pathological T0N1), two, and seven patients, respectively. Of the 29 patients with surgery, 23 received adjuvant nivolumab. At database lock, no patient had relapse and one died without relapse.

2019年10月至2021年6月，32例dMMR/MSI-H胃/GEJ腺癌患者入组。中位年龄为65.5岁(范围40-80岁)。临床分期为cT2-T3N0 (n=59)、cT2-T3N1 (n=522)、cT3N1M1 (n=51，错误纳入)。中位随访14.9个月(95%CI, 10.6 - 17.6)， 32例患者接受了新辅助免疫治疗(27例患者完成了所有周期)。6例患者(19%)发生新辅助治疗相关的3/4级不良事件。29名患者接受了手术;3名患者未接受手术，经无肿瘤活检和计算机断层扫描，内镜下完全缓解(2名患者拒绝手术，1名患者有转移)。手术发病率(Clavien-Dindo分类)为55%(1例术后死亡)。29例患者均R0切除，其中17例(58.6%;90%CI, 41.8 ~ 74.1)为pCR(病理T0N0)。Becker tumor regression分级为1a、1b、2、3的，分别为17例，3例(包括2例病理T0N1)、2例和7例。29例手术患者中，23例接受了nivolumab辅助治疗。数据库锁定时，无患者复发，1例无复发死亡。

CONCLUSION 结论

Nivolumab and ipilimumab-based neoadjuvant therapy is feasible and associated with no unexpected toxicity and a high pCR rate in patients with dMMR/MSI-H resectable gastric/GEJ adenocarcinoma

基于Nivolumab和ipilimumab的新辅助治疗在dMMR/MSI-H可切除的胃/GEJ腺癌患者中是可行的，具有高的pCR率并且没有意外的毒性。