Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Clin Colorectal Cancer. 2024 Dec;23(4):354-363.e4. doi: 10.1016/j.clcc.2024.05.006. Epub 2024 May 18.
Colorectal cancers (CRC) with BRAF V600E mutation exhibit limited chemotherapy response and a poor prognosis. Safety and efficacy of the VIC (Vemurafenib/Irinotecan/Cetuximab) regimen in the first-line setting for patients with BRAF V600E-mutated CRC remain undetermined.
In the prospective cohort study, the untreated, BRAF V600E-mutated, unresectable or metastatic CRC patients were enrolled. The VIC regimen and bevacizumab plus chemotherapy were compared in the first-line setting. The objective response rate (ORR), disease control rate (DCR), conversion resection rate, progression-free survival (PFS), and overall survival (OS) were evaluated.
In the intent-to-treat analysis, 38 patients received VIC regimen and 40 received bevacizumab plus chemotherapy. The ORR and DCR in the VIC group were significantly higher than in the bevacizumab-therapy group (ORR: 63.2% vs. 37.5%, P = .025; DCR: 94.7% vs. 75.0%, P = .019). The VIC regimen significantly outperformed bevacizumab plus chemotherapy in both PFS (11.9 vs. 7.7 months; hazard ratio [HR] = 0.51, 95% CI, 0.30-0.87; P = .010) and OS (25.3 vs. 14.6 months; HR = 0.43, 95% CI, 0.22-0.82; P = .011). In the VIC group, the conversion resection rate for liver metastases was 34.8% (8 of 23 patients), and for unresectable local CRC it was 54.5% (6 of 11 patients). The adverse events rates of Grade 3 to 4 were 34.2% and 32.5% for the VIC regimen and bevacizumab plus chemotherapy respectively.
Among Asian patients with BRAF V600E-mutated CRC, the VIC regimen showed favorable outcomes compared to bevacizumab plus chemotherapy in terms of tumor response and oncological survival, with a tolerable and manageable toxicity profile in the first-line setting.
携带 BRAF V600E 突变的结直肠癌（CRC）对化疗反应有限，预后不良。VIC（vemurafenib/irinotecan/cetuximab）方案在 BRAF V600E 突变 CRC 患者一线治疗中的安全性和疗效仍不确定。
在这项前瞻性队列研究中，入组了未经治疗、携带 BRAF V600E 突变、不可切除或转移性 CRC 患者。比较了 VIC 方案与贝伐珠单抗联合化疗在一线治疗中的疗效。评估了客观缓解率（ORR）、疾病控制率（DCR）、转化切除率、无进展生存期（PFS）和总生存期（OS）。
在意向治疗分析中，38 例患者接受了 VIC 方案治疗，40 例患者接受了贝伐珠单抗联合化疗。VIC 组的 ORR 和 DCR 明显高于贝伐珠单抗组（ORR：63.2%比 37.5%，P =.025；DCR：94.7%比 75.0%，P =.019）。VIC 方案在 PFS（11.9 比 7.7 个月；风险比 [HR] = 0.51，95%CI，0.30-0.87；P =.010）和 OS（25.3 比 14.6 个月；HR = 0.43，95%CI，0.22-0.82；P =.011）方面均显著优于贝伐珠单抗联合化疗。在 VIC 组中，肝转移转化切除率为 34.8%（23 例患者中的 8 例），不可切除局部 CRC 的转化率为 54.5%（11 例患者中的 6 例）。VIC 方案和贝伐珠单抗联合化疗的 3 级至 4 级不良事件发生率分别为 34.2%和 32.5%。
在亚洲 BRAF V600E 突变 CRC 患者中，与贝伐珠单抗联合化疗相比，VIC 方案在肿瘤反应和肿瘤生存方面具有更好的疗效，且在一线治疗中具有可耐受和可管理的毒性特征。
