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