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。
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：
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。
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