国际大咖说丨平衡毒性与疗效:ADC与其他疗法联合如何影响NSCLC的治疗前景?

健康   2024-11-06 18:23   北京  


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晚期非小细胞肺癌(NSCLC)的治疗策略包括铂类双药化疗、免疫疗法和靶向疗法,具体治疗手段取决于分子生物标志物的检测情况。晚期NSCLC患者目前尚未满足的医疗需求包括:接受免疫联合治疗失败后缺乏新的治疗选择,对靶向治疗产生耐药以及缺少改善疗效的策略[1-3]


本文作者:


Dr. Augusto Valdivia

西班牙巴塞罗那Vall d’Hebron大学医院

Vall d’Hebron肿瘤研究所


Dr. Patricia Iranzo

西班牙巴塞罗那Vall d’Hebron大学医院

Vall d’Hebron肿瘤研究所


Dr. Nuria Pardo

西班牙巴塞罗那Vall d’Hebron大学医院

Vall d’Hebron肿瘤研究所


Dr. Enriqueta Felip

西班牙巴塞罗那Vall d’Hebron大学医院

Vall d’Hebron肿瘤研究所


ADC是一种新兴药物,其治疗策略是向癌细胞递送强效的载荷,同时保护正常组织细胞,减少治疗相关不良事件(AE)并改善生活质量[4,5]目前,许多最近研发的ADC正在NSCLC中进行探索,其安全性各不相同(表1)[6-10]
优化ADC安全性的可能策略包括设置剂量上限(dose-capping)、分次给药(fractionated administration)和设置治疗持续时间上限(capping of treatment duration)[11]

表1. NSCLC ADC试验中报告的最常见的任何级别AE和≥3级AE

限制用药周期数

“限制用药周期数”是历史上研究化疗的一种策略,因为需要权衡疗效与毒性。多项试验已证实,在施用更多化疗周期时,未观察到反应率、生存结果或生活质量的改善[12-16]

研究人员在接受polatuzumab vedotin(抗CD79b抗体,含有单甲基auristatin E有效载荷的ADC)的患者中进行了事件发生时间(time-to-event)分析,从而探索“限制用药周期数”的策略。分析显示,当最多施用6~8个治疗周期时,≥2级周围神经病变(报告的主要限制性不良事件)的发生率显著下降[17]


“至应答时间(Time-to-response)”对于确定ADC“适当的用药周期数”也有参考价值。进行这些研究将有助于我们确认“限制用药周期数”对降低毒性和保持疗效的影响。

ADC联合免疫/靶向疗法

此外,“将ADC与免疫疗法或靶向疗法相结合”是一种目前正在研究的策略,旨在提高疗效并克服/预防患者发生耐药。重要的是,一些试验是在一线NSCLC患者中进行的。表2展示了正在进行的将ADC与免疫疗法或靶向疗法相联合的试验。[18-21]


表2. ADC与免疫或靶向疗法相结合的NSCLC试验


对于接受ADC联合免疫/靶向治疗的患者,在患者接受足够数量的ADC治疗周期后继续进行维持性免疫或靶向治疗,这可能是一个有前景的选择,如下所示。


图1. 诱导ADC联合免疫/靶向治疗,随后进行维持治疗的建议


总之,ADC的使用范围正在显著扩大,为免疫/靶向治疗失败的患者甚至一线NSCLC患者提供了可能的治疗选择。然而,ADC的应用过程也发现了新的药物毒性特征,需要找到减轻毒性的方法。“限制ADC给药次数,并将ADC与维持治疗结合使用”是值得探索的方向,以改善患者的生活质量。


参考文献

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《肿瘤瞭望》于2014年初创刊,由著名肿瘤科专家徐兵河院士担任总编辑,以“同步传真国际肿瘤进展”为办刊宗旨,以循证医学理念为指导思想,采用全媒体组合报道模式,致力于为国内广大肿瘤临床、教研人员搭建一座与国际接轨的桥梁。
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