Novel Therapeutics for Recurrent Cervical Cancer: Moving Towards Personalized Therapy
Novel Therapeutics for Recurrent Cervical Cancer: Moving Towards Personalized Therapy
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DOI：
10.1007/s40265-019-01249-z
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发表时间：
2020-02-01
期刊：
影响因子：
11.5
通讯作者：
Leath, Charles A., III
中科院分区：
文献类型：
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作者：
Cohen, Alexander C.;Roane, Brandon M.;Leath, Charles A., III
虽然筛查计划和HPV疫苗接种降低了宫颈癌的发病率，但美国每年仍有超过13，000例病例发生。早期宫颈癌具有良好的长期预后，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降低，并且两者都与较高的复发风险相关。对于持续性、复发性或转移性宫颈癌，几乎没有有效的治疗选择。2014年，基于III期GOG-240研究的结果，抗VEGF抗体贝伐珠单抗被批准与化疗联合使用。由于大多数宫颈癌都有病毒病因，这会损害免疫系统，因此使用检查点抑制剂和其他药物的免疫治疗似乎是一种有前途的方法。2018年6月，美国FDA批准抗PD 1抗体pembrolizumab用于在一线或多线化疗后进展的PD-L1表达的复发性或转移性宫颈癌。另一种抗PD 1抗体cemiplimab在这种情况下也显示出潜力，无论是作为单药治疗还是与放疗联合治疗，目前正在III期试验中进行评估。其他检查点抑制剂，包括nivolumab、durvalumab、atezolizumab和camrelizumab，正处于该疾病的不同临床开发阶段。最后，根据早期的研究结果，正在寻求的另一种靶向方法涉及PARP抑制剂（rucaparib和olaparib均处于II期）。
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.