Pecci Federica, Cantini Luca, Metro Giulio, Ricciuti Biagio, Lamberti Giuseppe, Farooqi Ammad Ahmad, Berardi Rossana
Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti di Ancona, Ancona, Italy.
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
Drugs Context. 2022 Aug 3;11. doi: 10.7573/dic.2022-4-1. eCollection 2022.
The treatment of non-small-cell lung cancer (NSCLC) harbouring mutations has witnessed some major breakthroughs in the last years. On the one hand, the recent advent of the third-generation tyrosine kinase inhibitor (TKI) osimertinib has reshaped the therapeutic algorithm both in the first-line and adjuvant settings for patients with common activating Ex19del and L858R mutations. On the other hand, the availability of new comprehensive next-generation sequencing panels, to be used on tumour tissue or on liquid biopsy, has revealed the existence of uncommon as well as compound mutations that partially explain the onset of resistance. Nevertheless, dissecting the biological mechanisms underlying primary and secondary resistance to EGFR-TKIs is crucial to developing alternative therapeutic strategies and further improving patient outcomes. Herein, we provide an updated and comprehensive summary of the latest advancements in the quest for compounds targeting -mutant advanced non-small-cell lung cancer, discussing the biological rationale underlying the development of a forefront combination of TKI and/or new antibody-drug conjugates. We also suggest a treatment algorithm that could be followed considering the latest published data.
在过去几年中，携带特定突变的非小细胞肺癌（NSCLC）的治疗取得了一些重大突破。一方面，第三代酪氨酸激酶抑制剂（TKI）奥希替尼的近期问世重塑了针对常见激活型Ex19del和L858R突变患者的一线和辅助治疗方案。另一方面，可用于肿瘤组织或液体活检的新型全面二代测序panel的出现，揭示了罕见以及复合突变的存在，这些突变部分解释了耐药性的发生。然而，剖析对EGFR-TKIs原发和继发耐药的生物学机制对于开发替代治疗策略和进一步改善患者预后至关重要。在此，我们提供了一份最新且全面的总结，内容涉及针对特定突变的晚期非小细胞肺癌寻找化合物的最新进展，讨论了TKI和/或新型抗体药物偶联物前沿联合治疗开发的生物学原理。我们还根据最新发表的数据提出了一种可遵循的治疗方案。
