背景:具有BRAFV600E突变的结直肠癌(CRC)表现出有限的化疗反应和不良预后。VIC(Vemurafenib/伊立替康/西妥昔单抗)方案在一线环境中对BRAFV600E突变的CRC患者的安全性和有效性仍未确定。
方法:在前瞻性队列研究中,未经处理的,BRAFV600E突变,纳入不可切除或转移性CRC患者.在一线设置中比较VIC方案和贝伐单抗加化疗。客观反应率(ORR),疾病控制率(DCR),转换切除率,无进展生存期(PFS),评估总生存期(OS)。
结果:在意向治疗分析中,38例患者接受VIC方案,40例接受贝伐单抗联合化疗。VIC组的ORR和DCR明显高于贝伐单抗治疗组(ORR:63.2%vs.37.5%,P=.025;DCR:94.7%vs.75.0%,P=.019)。在两个PFS中,VIC方案均显着优于贝伐单抗加化疗(11.9vs.7.7个月;风险比[HR]=0.51,95%CI,0.30-0.87;P=.010)和OS(25.3vs.14.6个月;HR=0.43,95%CI,0.22-0.82;P=.011)。在VIC集团,肝转移的转化切除率为34.8%(23例患者中有8例),不可切除的局部CRC为54.5%(11例患者中有6例).VIC方案和贝伐单抗联合化疗的3~4级不良事件发生率分别为34.2%和32.5%。
结论:在BRAFV600E突变CRC的亚洲患者中,与贝伐单抗联合化疗相比,VIC方案在肿瘤反应和肿瘤生存方面显示出良好的结局,在一线设置中具有可耐受和可控制的毒性特征。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.