结直肠癌 (CRC) 是全球第三大流行癌症，对临床医生构成了严峻挑战。先前的研究表明，在接受（程序性细胞死亡蛋白 1）PD-1 抑制剂联合瑞戈非尼治疗后，微卫星稳定的微卫星稳定 CRC 患者对化疗无效。在此，我们报告了一个独特的病例，该患者常规化疗和放疗无效，但通过瑞戈非尼和 PD-1 抑制剂信迪利单抗的三线治疗显示病情长期稳定。一名 64 岁的东亚女性患者因大便频率增加和大便带血而出现腹部不适而入院。肛门指检发现腺癌，而肿瘤切除的遗传分析检测到密码子 12 和 13 中的野生型 KRAS 突变。用于检测（错配修复）MMR 基因种系突变的微卫星不稳定性（MSI）分析显示稳定的表型。2016 年 12 月，进行了 Miles 切除肠粘连松解术和直肠髂血管探查术（肿瘤、淋巴结、转移 [TNM]：T3N0M0；IIA 期）。辅助化疗方案包括 1.5 g 卡培他滨（每天两次）和 200 mg 奥沙利铂治疗的组合，从 2016 年 2 月开始，共三个周期；随后口服卡培他滨片（1.5 g 两次），连续五个周期作为术后姑息治疗。该患者的肝 C 病毒检测呈阳性，该病毒通过口服抗病毒药物治疗。在 4 年后直肠腺癌复发并在先前的化疗方案中出现疾病进展后，每天一次给予瑞戈非尼 120 mg 联合信迪利单抗 200 mg，并监测患者的进展。2020 年 3 月的后续计算机断层扫描成像显示疾病进展，另外出现结节形成（TNM：T3NxM1b；IVB 期）。根据实体瘤反应评估标准（RECIST），患者在接受瑞戈非尼和信迪利单抗免疫治疗后显示完全反应（CR）。该临床病例报告的数据支持未来探索口服多激酶抑制剂瑞戈非尼与 PD-1 靶向单克隆抗体联合治疗转移性微卫星稳定 CRC 患者。
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. 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. 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.
