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期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2400634

摘要内容如下：

背景

错配修复缺陷（DMMR）肿瘤可在10%至15%的非转移性结肠癌患者中发现。在这些患者中，化疗的疗效有限。新辅助免疫疗法的使用已经显示出有希望的结果，但这种方法的研究数据有限。

方法

我们进行了一项2期研究，在该研究中，非转移性、局部晚期、既往未经治疗的DMMR结肠癌患者接受了新辅助治疗nivolumab联合ipilimumab。两个主要终点是安全性，定义为及时手术（即由于治疗相关毒性事件导致计划手术延迟≤2周）和3年无病生存率。次要终点包括病理反应和基因组分析结果。

结果

在115名入选患者中，113名（98%；97.5%可信区间[CI]，93-100）及时手术；2例患者手术延迟2周以上。5名患者（4%）发生了3级或4级免疫相关不良事件，没有患者因不良事件而停止治疗。在纳入疗效分析的111例患者中，观察到109例（98%；95%CI，94-100），包括105例（95%）主要病理缓解（定义为≤10%肿瘤残留）和75例（68%）病理完全缓解（0%肿瘤残留）。中位随访时间为26个月（范围为9至65个月），无患者复发。

结论

在局部晚期DMMR结肠癌患者中，新辅助治疗nivolumab联合ipilimumab具有可接受的安全性，并在高比例的患者中导致病理反应。（由Bristol Myers Squibb资助；NICHE-2 ClinicalTrials.gov编号，NCT03026140。）

英文原文如下：

Abstracts

BACKGROUND  Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited.

METHODS  We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., ≤2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses.

RESULTS  Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94 to 100), including 105 (95%) with a major pathological response (defined as ≤10% residual viable tumor) and 75 (68%) with a pathological complete response (0% residual viable tumor). With a median follow-up of 26 months (range, 9 to 65), no patients have had recurrence of disease.

CONCLUSIONS  In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.).

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