Lemaire C, Boileve A, Manceau G, Coutzac C, Muller M, Girot P, Lellouche L, Saltel-Fulero A, Lagorce-Pages C, Gallois C, Gandini A, Karoui M, Taieb J, Palle J
Université Paris Cité, Department of Digestive Oncology, CARPEM Comprehensive Cancer Center, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Department of Medical Oncology, Gustave Roussy, INSERM U1279, Villejuif, France; Université Paris Saclay, Orsay, France.
ESMO Open. 2025 Jul 31;10(8):105516. doi: 10.1016/j.esmoop.2025.105516.
Several studies showed that in mismatch repair-deficient (dMMR)/microsatellite instability (MSI) nonmetastatic colon cancer (CC), neoadjuvant immune checkpoint inhibitors (ICIs) were associated with exceptional rates of pathological major response (pMR) and complete response (pCR). Patients included in these trials, however, were highly selected, and real-life data are now needed to better evaluate the efficacy and tolerability of neoadjuvant ICIs in routine clinical practice.
This retrospective observational study aimed to describe the clinical practices regarding ICIs in the neoadjuvant setting for patients with dMMR/MSI nonmetastatic CC, and to evaluate their efficacy and safety in real-world conditions. Patients receiving ICIs as part of a therapeutic trial were excluded.
Between 2019 and 2024, 32 patients were included across six French centers [median age 70 years (range 51-76 years), Lynch syndrome 31%]. Twenty-four patients had right-sided CC (85%), including three (9%) with two primary tumor locations. Ten patients (31%) received ipilimumab + nivolumab (NICHE regimen), while 22 (69%) were treated with pembrolizumab monotherapy. Grade ≥3 toxicities were observed in six patients (19%), including one toxic death and three toxicities (9%) leading to treatment discontinuation (one rheumatoid polyarthritis-like syndrome and two tumor fistulizations). Three patients developed bowel obstruction while receiving ICIs, two of whom underwent surgery showing pCR and pMR. Thirty patients were resected and 33 tumors were analyzed histologically with pMR in 21 cases (64%) including pCR in 14 cases (42%). The presence of an independent-cells contingent was statistically associated with poor pathological response.
This retrospective real-world study confirms the excellent results of neoadjuvant ICIs in dMMR/MSI nonmetastatic CC patients. pMR and pCR rates were, however, lower than those published in previous studies (64% and 42%, respectively), with higher rates of grade ≥3 toxicity, including one potential toxic death and three treatment discontinuations.
多项研究表明，在错配修复缺陷（dMMR）/微卫星高度不稳定（MSI）的非转移性结肠癌（CC）中，新辅助免疫检查点抑制剂（ICI）与极高的病理主要缓解（pMR）率和完全缓解（pCR）率相关。然而，纳入这些试验的患者经过了高度筛选，现在需要真实世界的数据来更好地评估新辅助ICI在常规临床实践中的疗效和耐受性。
这项回顾性观察性研究旨在描述dMMR/MSI非转移性CC患者新辅助治疗中ICI的临床应用情况，并评估其在现实世界中的疗效和安全性。接受ICI作为治疗试验一部分的患者被排除。
2019年至2024年期间，法国6个中心共纳入32例患者[中位年龄70岁（范围51 - 76岁），林奇综合征占31%]。24例患者为右侧CC（85%），其中3例（9%）有两个原发肿瘤部位。10例患者（31%）接受了伊匹木单抗 + 纳武单抗（NICHE方案），而22例（69%）接受了帕博利珠单抗单药治疗。6例患者（19%）出现≥3级毒性反应，包括1例毒性死亡和3例导致治疗中断的毒性反应（1例类风湿性关节炎样综合征和2例肿瘤瘘管形成）。3例患者在接受ICI治疗时出现肠梗阻，其中2例接受手术，显示为pCR和pMR。30例患者接受了手术切除，对33个肿瘤进行了组织学分析，21例（64%）出现pMR，其中14例（42%）为pCR。独立细胞群的存在与病理反应不佳在统计学上相关。
这项回顾性真实世界研究证实了新辅助ICI在dMMR/MSI非转移性CC患者中的优异结果。然而，pMR和pCR率低于先前研究报道的水平（分别为64%和42%），≥3级毒性反应发生率更高，包括1例潜在的毒性死亡和3例治疗中断。
