Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Medical Oncology of Zhengzhou University Affiliated Cancer Hospital, Henan Cancer Hospital, Zhengzhou, Henan, China.
JAMA Netw Open. 2020 Jul 1;3(7):e2011036. doi: 10.1001/jamanetworkopen.2020.11036.
Fluorouracil-based chemotherapy combined with anti-epidermal growth factor receptor/vascular endothelial growth factor therapy is the standard first-line treatment for metastatic colorectal cancer followed by low-intensity maintenance therapy to balance the clinical efficacy and adverse effects (AEs). However, there have been concerns about the AEs of capecitabine plus cetuximab as a maintenance therapy in patients with RAS wild-type metastatic colorectal cancer.
To evaluate the biological activity and safety of capecitabine plus cetuximab as a novel maintenance therapy for RAS wild-type metastatic colorectal cancer.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2 prospective clinical trial was conducted from April 29, 2016, to April 29, 2019, at 5 centers in China. Patients diagnosed as having RAS wild-type metastatic colorectal cancer were recruited to receive fluorouracil-based cytotoxic agents combined with cetuximab followed by capecitabine plus cetuximab for maintenance therapy. Forty-seven patients with histologically confirmed metastatic colorectal cancer and genetic test results showing a wild-type RAS were enrolled in maintenance therapy.
Induction therapy for patients with RAS wild-type metastatic colorectal cancer was 8 to 12 cycles of fluorouracil-based chemotherapy combined with cetuximab. After stable disease status or better was achieved, reduced-dose capecitabine plus cetuximab was administered for maintenance therapy.
The primary end point was progression-free survival during maintenance therapy. The secondary end points were total progression-free survival, overall survival, quality of life, safety, and toxic effects of treatment.
Forty-seven patients were enrolled in maintenance therapy, with a median age of 52 years (range, 25-81 years) and 32 (68%) of them being men. The median maintenance progression-free survival was 7.2 (95% CI, 5.8-8.6) months. The median progression-free survival was 12.7 (95% CI, 11.8-15.4) months. The median overall survival was 27.4 (95% CI, 21.4-35.5) months. Grade 3 to 4 AEs during induction therapy included neutropenia (4 patients [9%]), diarrhea (4 patients [9%]), nausea or vomiting (3 patients [6%]), rash acneiform (10 patients [21%]), and hand-foot syndrome (8 patients [17%]). Grade 3 to 4 AEs during maintenance therapy included diarrhea (2 patients [4%]), rash acneiform (8 patients [17%]), and hand-foot syndrome (5 patients [11%]).
Reduced-dose capecitabine plus cetuximab after initial chemotherapy is a novel maintenance therapy for patients with RAS wild-type metastatic colorectal cancer that achieved good outcomes and tolerable nonserious AEs.
ClinicalTrials.gov Identifier: NCT02717923.
重要性：氟尿嘧啶为基础的化疗联合抗表皮生长因子受体/血管内皮生长因子治疗是转移性结直肠癌的标准一线治疗方法，随后进行低强度维持治疗以平衡临床疗效和不良反应（AE）。然而，卡培他滨联合西妥昔单抗作为 RAS 野生型转移性结直肠癌维持治疗的 AE 一直存在担忧。
目的：评估卡培他滨联合西妥昔单抗作为 RAS 野生型转移性结直肠癌新型维持治疗的生物学活性和安全性。
设计、地点和参与者：这是一项从 2016 年 4 月 29 日至 2019 年 4 月 29 日在中国 5 个中心进行的 2 期前瞻性临床试验。招募了诊断为 RAS 野生型转移性结直肠癌的患者，接受氟尿嘧啶为基础的细胞毒性药物联合西妥昔单抗治疗，然后接受卡培他滨联合西妥昔单抗维持治疗。47 例经组织学证实的转移性结直肠癌患者和基因检测结果显示 RAS 野生型的患者入组维持治疗。
干预措施：RAS 野生型转移性结直肠癌患者的诱导治疗为 8-12 周期的氟尿嘧啶为基础的化疗联合西妥昔单抗。在疾病稳定或更好的状态下，给予低剂量卡培他滨联合西妥昔单抗维持治疗。
主要终点和次要终点：主要终点是维持治疗期间的无进展生存期。次要终点包括总无进展生存期、总生存期、生活质量、安全性和治疗毒性。
结果：47 例患者入组维持治疗，中位年龄为 52 岁（范围 25-81 岁），32 例（68%）为男性。中位维持无进展生存期为 7.2 个月（95%CI，5.8-8.6）。中位无进展生存期为 12.7 个月（95%CI，11.8-15.4）。中位总生存期为 27.4 个月（95%CI，21.4-35.5）。诱导治疗期间发生的 3-4 级 AE 包括中性粒细胞减少症（4 例[9%]）、腹泻（4 例[9%]）、恶心或呕吐（3 例[6%]）、痤疮样皮疹（10 例[21%]）和手足综合征（8 例[17%]）。维持治疗期间发生的 3-4 级 AE 包括腹泻（2 例[4%]）、痤疮样皮疹（8 例[17%]）和手足综合征（5 例[11%]）。
结论：初始化疗后给予卡培他滨联合西妥昔单抗的低剂量治疗是 RAS 野生型转移性结直肠癌的一种新型维持治疗方法，可获得良好的疗效和可耐受的非严重 AE。
试验注册：ClinicalTrials.gov 标识符：NCT02717923。
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