肺癌适应性治疗:未来研究方向

Adaptive lung cancer therapy:future perspectives

基于精准医学原则,肺癌已经形成基于分子分型进行个体化管理的模式,未满足的临床需求进一步衍生了个体化治疗的新概念,即适应性治疗(adaptive therapy)。适应性治疗的定义是在标准治疗的基础上,基于生物标志物动态变化精准地筛选患者进行治疗的加减,目的是在获得更佳的治疗效果之时,兼顾患者的生活质量及获得更好的成本效益。其中生物标志物需要在特定的临床场景下进行验证,从而用于动态、稳定地预测疾病无复发或无进展,或预测治疗疗效。适应性治疗的临床应用场景一般是经过治疗后,影像学无可见或无可代谢的肿瘤病灶的状态。具体包括早期携带表皮生长因子受体(epidermal growth factor receptor,EGFR)突变非小细胞肺癌(non-small cell lung cancer,NSCLC)经完全性手术切除后、早期驱动基因阴性NSCLC完全性手术切除术后、局晚期驱动基因阴性NSCLC同步放化疗后及晚期“药物假期”策略等,探索降阶治疗的可能,其中循环肿瘤DNA-微小残留病灶(circulating tumor DNA-minimal residual disease,ctDNA-MRD)是重要的生物标志物。升阶治疗策略则仍然在研究阶段。未来值得探索的方向包括筛选出基于标准治疗无法满足需求的患者,同时采用生物标志物指导治疗,为患者带来最具性价比的个体化策略。

In the era of precision medicine,patients with lung cancer receive molecular subtype-based personalized management.The unmet clinical need initiated the concept of adaptive therapy,a novel personalized treatment strategy referring to the biomarker-directed treatment escalation or de-escalation based on the standard of care,aiming to improve efficacy,quality of life,and cost efficiency.Biomarkers are validated under specific clinical scenarios to dynamically and stably predict disease-free status or efficacy.The optimal clinical scen-arios for adaptive therapy comprises post-treatment and radiologically lesion-free or metabolically inactive disease status.Several promising clinical situations are exploring de-escalation therapy,including epidermal growth factor receptor(EGFR)-mutated,totally resected non-small cell lung cancer(NSCLC),driver gene-negative,totally resected NSCLC,driver gene-negative,radiochemotherapy-treated,locally advanced NSCLC,and drug holidays for metastatic NSCLC.Therefore,circulating tumor DNA-minimal residual disease,(ctDNA-MRD)is considered an important biomarker.Concerning escalation therapy,this field is less well-supported with results,demanding further exploration.Related to future perspectives,more effort should be invested in focusing on patients with unmet clinical needs,even those with a standard of care,and providing biomarker-based adaptive therapy for efficacy and efficiency improvement.