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索凡替尼联合 PD-1 抑制剂信迪利单抗治疗微卫星稳定型难治性结直肠癌患者的长期生存:一例病例报告及文献复习。

Long-term survival of a patient with microsatellite-stable refractory colorectal cancer with regorafenib and PD-1 inhibitor sintilimab: a case report and review of literature.

机构信息

Department of Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, No 127, Dongming Road, Jinshui District, Zhengzhou City, 450003, Henan Province, China.

出版信息

BMC Gastroenterol. 2021 Oct 23;21(1):399. doi: 10.1186/s12876-021-01950-y.

Abstract

BACKGROUND

Colorectal cancer (CRC) is the third most prevalent cancer worldwide and poses a serious challenge for clinicians. Previous studies have shown promising results in patients with Microsatellite Stable microsatellite-stable CRC refractory to chemotherapy upon treating with (Programmed Cell Death Protein 1) PD-1 inhibitor combined with regorafenib. Herein, we report a unique case of a patient for whom the conventional chemotherapy and radiotherapy were ineffective, but showed a prolonged stable disease with third-line treatment with regorafenib and PD-1 inhibitor, sintilimab.

CASE PRESENTATION

A 64-year-old East Asian female patient was admitted to a regional cancer hospital presenting with abdominal unease due to increased stool frequency and bloody stool. Digital anal examination revealed adenocarcinoma, while genetic profiling of the tumor resections detected wild-type KRAS mutations in codon 12 and 13. Microsatellite instability (MSI) analysis for detecting germline mutations of (Mismatch-repair) MMR genes showed stable phenotype. In December 2016, Miles' resection for intestinal adhesion release and iliac vessel exploration in the rectum was performed (Tumor, Node, Metastasis [TNM]: T3N0M0; stage IIA). The adjuvant chemotherapeutic regimen consisted of a combination of capecitabine at 1.5 g (twice daily) and oxaliplatin therapy at 200 mg for three cycles from February 2016; followed by administering capecitabine tablets orally (1.5 g bid) for five cycles as post-operative palliative care. The patient tested positive for hepatic C virus, which was managed by oral antiviral agents. Following recurrence of rectal adenocarcinoma after 4 years and disease progression with a previous chemotherapeutic regimen, regorafenib was administered at 120 mg once daily combined with sintilimab 200 mg, and the patient's progress was monitored. A follow-up computerized tomography imaging in March 2020 showed disease progression, additionally presented nodule formation (TNM: T3NxM1b; stage IVB). According to Response Evaluation Criteria in Solid Tumors criteria (RECIST), the patient showed a complete response (CR) after treatment with regorafenib and sintilimab immunotherapy.

CONCLUSION

Data from this clinical case report support future exploration of combination treatment of the oral multi-kinase inhibitor regorafenib with PD-1 targeted monoclonal antibodies in patients with metastatic microsatellite-stable CRC.

摘要

背景

结直肠癌(CRC)是全球第三大常见癌症,对临床医生构成严重挑战。先前的研究表明,对于微卫星稳定(Microsatellite Stable,MSS)的 CRC 患者,在接受化疗后出现耐药,使用程序性死亡蛋白 1(PD-1)抑制剂联合regorafenib 治疗有较好的效果。在此,我们报告一例患者,其常规化疗和放疗均无效,但三线治疗使用regorafenib 和 PD-1 抑制剂 sintilimab 后疾病得到了长时间的稳定控制。

病例介绍

一名 64 岁东亚女性患者因大便频数和便血而到一家地区癌症医院就诊。肛门指诊发现腺癌,肿瘤切除标本的基因谱分析显示 KRAS 密码子 12 和 13 存在野生型突变。微卫星不稳定性(Microsatellite Instability,MSI)分析用于检测错配修复(Mismatch-repair,MMR)基因的种系突变,结果显示为稳定表型。2016 年 12 月,行 Miles 直肠粘连松解及髂血管探查术(肿瘤、淋巴结、转移 [Tumor, Node, Metastasis,TNM]:T3N0M0;IIA 期)。辅助化疗方案为卡培他滨 1.5 g(每日 2 次)联合奥沙利铂治疗,共 3 个周期,于 2016 年 2 月开始;随后行卡培他滨片(1.5 g,每日 2 次)5 个周期的术后姑息治疗。患者丙型肝炎病毒检测阳性,采用口服抗病毒药物治疗。4 年后直肠腺癌复发,且先前的化疗方案出现疾病进展,随后给予regorafenib 120 mg 每日 1 次联合 sintilimab 200 mg 治疗,并对患者的病情进行监测。2020 年 3 月的计算机断层扫描影像学检查显示疾病进展,同时出现结节形成(TNM:T3NxM1b;IVB 期)。根据实体瘤疗效评价标准(Response Evaluation Criteria in Solid Tumors,RECIST),该患者在接受 regorafenib 和 sintilimab 免疫治疗后达到完全缓解(Complete Response,CR)。

结论

本病例报告的数据支持进一步探索口服多激酶抑制剂 regorafenib 联合 PD-1 靶向单克隆抗体治疗转移性 MSS CRC 患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6173/8542310/b9fbc4e31927/12876_2021_1950_Fig1_HTML.jpg

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