复发转移性宫颈癌药物治疗的新进展

New Progress in Drug Treatment of Recurrent and Metastatic Cervical Cancer

摘要: 血管内皮生长因子(VEGF)已经成为包括宫颈癌在内的多种恶性肿瘤的治疗靶点。化疗联合完全人源化单克隆抗体——贝伐珠单抗，现已成为复发转移性宫颈癌患者的治疗选择。III期随机试验GOG 240结果显示化疗联合贝伐单抗，可以明显提高总生存期及无进展生存期(PFS17.0 vs. 13.3个月)，不增加不良反应。GOG 240研究结果显示贝伐单抗的治疗效果与患者不良预后因素及循环肿瘤细胞有关，存在高中危预后不良因素者对贝伐单抗治疗反应良好。循环肿瘤细胞量与贝伐单抗治疗效果相关，可以作为贝伐单抗治疗效果评估的生物标记物。不可否认阴道瘘是与贝伐单抗使用相关的不良事件。复发性转移性宫颈癌药物治疗的另一个飞跃是免疫治疗，以免疫检查点为靶点，免疫检查点抑制剂通过PD-1/PD-L1通路来打破免疫耐受，对部分晚期宫颈癌有效，但仍需要大量临床数据对其治疗选择、适应症、禁忌症进行评价。抗血管生成及免疫检查点抑制剂为复发转移性宫颈癌患者带来一缕曙光，但其并发症值得关注。广泛临床应用还需要积累更多的临床数据。

Abstract: Vascular endothelial growth factor (VEGF) has become a therapeutic target for several malignancies, including cervical cancer. Chemotherapy combined with a fully humanized monoclonal anti-body—bevacizumab, has become the treatment of choice for patients with recurrent and metastatic cervical cancer. The regulatory approval for this indication was based on the Phase III randomized trial GOG 240, which showed statistically and clinically significant improvement in overall survival after the addition of bevacizumab to chemotherapy: 17.0 vs. 13.3 months. The addition of bevacizumab significantly improved progression-free survival without affecting quality of life. GOG 240 confirmed that the treatment effect of bevacizumab was related to poor prognostic factors, and those with medium to high risk prognosis responded well to bevacizumab treatment. Circulating tumor cells can be used as biomarkers to evaluate the efficacy of bevacizumab therapy. Vaginal fistula is an adverse event associated with bevacizumab. Immunotherapy has entered clinical trials to address the clinical need for effective and tolerated second-line treatment in this patient population. Targeted by immune checkpoints, immune checkpoint inhibitors break immune tolerance through the PD-1/PD-L1 pathway, and are effective against some advanced cervical cancer, but a large number of clinical data are needed to evaluate treatment options, indications, and contraindications. Anti-angiogenesis and immune checkpoint inhibitors bring dawn to patients with recurrent or metastatic cervical cancer, but their complications deserve attention. Extensive clinical applications need more clinical data.