Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, 1700 6th Avenue South, Room 10250, Birmingham, AL, 35249-7333, USA.
Drugs. 2020 Feb;80(3):217-227. doi: 10.1007/s40265-019-01249-z.
While screening programs and HPV vaccination have decreased the incidence of cervical cancer, still over 13,000 cases occur in the USA annually. Early-stage cervical cancer has an excellent long-term prognosis, with 5-year survival for localized disease being > 90%. Survival decreases markedly for both locally advanced and metastatic disease, and both are associated with a higher risk of recurrence. Few effective treatment options exist for persistent, recurrent, or metastatic cervical cancer. In 2014, the anti-VEGF antibody bevacizumab was approved in combination with chemotherapy based on the results of the Phase III GOG-240 study. As the majority of cervical cancers have a viral etiology, which impairs the immune system, immunotherapy using checkpoint inhibitors and other agents, appears to be a promising approach. In June 2018, the US FDA approved the anti-PD1 antibody pembrolizumab for recurrent or metastatic cervical cancer with PD-L1 expression that progressed after one or more lines of chemotherapy. Another anti-PD1 antibody, cemiplimab also shows potential in this setting, either as monotherapy or combined with radiotherapy, and it is currently being evaluated in a Phase III trial. Additional checkpoint inhibitors including nivolumab, durvalumab, atezolizumab, and camrelizumab are in different stages of clinical development for the disease. Finally, an additional targeted approach being pursued involves PARP inhibitors (rucaparib and olaparib are both in Phase II) based on earlier study results.
虽然筛查计划和 HPV 疫苗接种已经降低了宫颈癌的发病率，但在美国每年仍有超过 13000 例病例发生。早期宫颈癌具有极好的长期预后，局部疾病的 5 年生存率>90%。局部晚期和转移性疾病的生存率显著下降，两者都与更高的复发风险相关。对于持续性、复发性或转移性宫颈癌，有效的治疗选择很少。2014 年，基于 III 期 GOG-240 研究的结果，抗 VEGF 抗体贝伐珠单抗联合化疗获得批准用于治疗宫颈癌。由于大多数宫颈癌具有病毒病因，会损害免疫系统，因此使用免疫检查点抑制剂和其他药物的免疫疗法似乎是一种很有前途的方法。2018 年 6 月，美国 FDA 批准抗 PD-1 抗体派姆单抗用于 PD-L1 表达阳性的复发性或转移性宫颈癌，这些患者在接受一线或多线化疗后进展。另一种抗 PD-1 抗体西米普利单抗在这种情况下也有潜力，无论是单药治疗还是联合放疗，目前正在进行 III 期临床试验。其他检查点抑制剂，包括纳武单抗、度伐单抗、阿替利珠单抗和卡瑞利珠单抗，都处于针对该疾病的不同临床开发阶段。最后，一种正在探索的额外靶向方法是基于早期研究结果的 PARP 抑制剂（鲁卡帕尼和奥拉帕尼均处于 II 期）。
