新辅助纳武利尤单抗联合伊匹单抗和辅助纳武利尤单抗治疗局部缺陷错配修复/微卫星不稳定高型胃或胃食管结合部腺癌：GERCOR NEONIPIGA Ⅱ期研究。

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.

机构信息

Sorbonne University, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, INSERM 938, SIRIC CURAMUS, Paris, France.

Department of Hepatology and Gastroenterology, Poitiers University Hospital, Poitiers, France.

出版信息

J Clin Oncol. 2023 Jan 10;41(2):255-265. doi: 10.1200/JCO.22.00686. Epub 2022 Aug 15.

DOI:10.1200/JCO.22.00686

PMID:35969830

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9839243/

Abstract

PURPOSE

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).

PATIENTS AND METHODS

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.

RESULTS

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 = 9), cT2-T3N1 (n = 22), and cT3N1M1 (n = 1, wrongly included). With a median follow-up of 14.9 months (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 an R0 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.

CONCLUSION

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.

摘要

目的

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类为基础的化疗是标准治疗。围手术期化疗对于错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H）的胃/GEJ 腺癌仍存在争议。

患者和方法

NEONIPIGA（ClinicalTrials.gov 标识符：NCT04006262）是一项 II 期研究，评估了新辅助纳武利尤单抗 240 mg，每两周一次×6 次和伊匹单抗 1 mg/kg，每六周一次×2 次，随后进行手术和辅助纳武利尤单抗 480 mg，每四周一次（九次注射），用于局部晚期可切除 dMMR/MSI-H、临床（c）肿瘤（T）2-T4 淋巴结（N）x 转移（M）0 胃/GEJ 腺癌患者。主要终点是病理完全缓解（pCR）率。

结果

2019 年 10 月至 2021 年 6 月，共纳入 32 例 dMMR/MSI-H 胃/GEJ 腺癌患者。中位年龄为 65.5 岁（范围：40-80 岁）。临床分期为 cT2-T3N0（n=9）、cT2-T3N1（n=22）和 cT3N1M1（n=1，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 例完成了所有周期）。6 例（19%）发生新辅助治疗相关的 3/4 级不良事件。29 例患者接受了手术；3 例未手术，内镜下完全缓解，活检未见肿瘤，计算机断层扫描正常（2 例拒绝手术，1 例入组时转移）。手术发病率（Clavien-Dindo 分级）为 55%（1 例术后死亡）。所有 29 例患者均行 R0 切除术，17 例（58.6%；90%CI：41.8-74.1）达到 pCR（病理 T0N0）。17 例患者的 Becker 肿瘤消退分级为 1a、1b、2 和 3，3 例（包括 2 例病理 T0N1）、2 例和 7 例患者分别为 2、2 和 7。在 29 例接受手术的患者中，23 例接受了辅助纳武利尤单抗治疗。在数据锁定时，没有患者复发，1 例患者死亡但无复发。