Abstract：
Immune-checkpoint inhibitors (IO) have significantly improved outcomes of patients with non-oncogene-addicted non-small cell lung cancer (NSCLC), becoming the first-line agents for advanced disease. However, resistance remains a significant clinical challenge, limiting their effectiveness.
Hereby, we addressed standard and innovative therapeutic approaches for NSCLC patients experiencing progression after IO treatment, discussing the emerging resistance mechanisms and the ongoing efforts to overcome them. In order to provide a complete overview of the matter, we performed a comprehensive literature search across prominent databases, including PubMed, EMBASE (Excerpta Medica dataBASE), and the Cochrane Library, and a research of the main ongoing studies on clinicaltrials.gov.
The dynamics of progression to IO, especially in terms of time to treatment failure and burden of progressive disease, should guide the best subsequent management, together with patient clinical conditions. Long-responders to IO might benefit from continuation of IO beyond-progression, in combination with other treatments. Patients who experience early progression should be treated with salvage CT in case of preserved clinical conditions. Finally, patients who respond to IO for a considerable timeframe and who later present oligo-progression could be treated with a multimodal approach in order to maximize the benefit of immunotherapy.
Hereby, we addressed standard and innovative therapeutic approaches for NSCLC patients experiencing progression after IO treatment, discussing the emerging resistance mechanisms and the ongoing efforts to overcome them. In order to provide a complete overview of the matter, we performed a comprehensive literature search across prominent databases, including PubMed, EMBASE (Excerpta Medica dataBASE), and the Cochrane Library, and a research of the main ongoing studies on clinicaltrials.gov.
The dynamics of progression to IO, especially in terms of time to treatment failure and burden of progressive disease, should guide the best subsequent management, together with patient clinical conditions. Long-responders to IO might benefit from continuation of IO beyond-progression, in combination with other treatments. Patients who experience early progression should be treated with salvage CT in case of preserved clinical conditions. Finally, patients who respond to IO for a considerable timeframe and who later present oligo-progression could be treated with a multimodal approach in order to maximize the benefit of immunotherapy.
摘要：
■免疫检查点抑制剂（IO）可显著改善非癌基因成瘾的非小细胞肺癌（NSCLC）患者的预后，成为晚期疾病的一线药物。然而,耐药性仍然是一个重大的临床挑战，限制其有效性。
■特此，我们为IO治疗后进展的NSCLC患者提供了标准和创新的治疗方法，讨论正在出现的抵抗机制以及正在进行的克服这些机制的努力。为了提供对此事的完整概述，我们在著名的数据库中进行了全面的文献检索，包括PubMed,EMBASE（摘录医学数据库），还有Cochrane图书馆,以及一项关于临床试验的主要正在进行的研究。
■发展到IO的动态，特别是在治疗失败的时间和疾病进展的负担方面，应该指导最好的后续管理，以及患者的临床状况。IO的长期响应者可能会受益于IO的持续超越进展，与其他治疗相结合。在保留临床条件的情况下，出现早期进展的患者应接受挽救性CT治疗。最后,在相当长的时间范围内对IO有反应并且后来出现寡核进展的患者可以采用多模式方法进行治疗,以最大限度地提高免疫治疗的益处.
■特此，我们为IO治疗后进展的NSCLC患者提供了标准和创新的治疗方法，讨论正在出现的抵抗机制以及正在进行的克服这些机制的努力。为了提供对此事的完整概述，我们在著名的数据库中进行了全面的文献检索，包括PubMed,EMBASE（摘录医学数据库），还有Cochrane图书馆,以及一项关于临床试验的主要正在进行的研究。
■发展到IO的动态，特别是在治疗失败的时间和疾病进展的负担方面，应该指导最好的后续管理，以及患者的临床状况。IO的长期响应者可能会受益于IO的持续超越进展，与其他治疗相结合。在保留临床条件的情况下，出现早期进展的患者应接受挽救性CT治疗。最后,在相当长的时间范围内对IO有反应并且后来出现寡核进展的患者可以采用多模式方法进行治疗,以最大限度地提高免疫治疗的益处.
