McCusker Michael G, Russo Alessandro, Scilla Katherine A, Mehra Ranee, Rolfo Christian
University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA; Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy.
ESMO Open. 2019 Jul 20;4(Suppl 2):e000524. doi: 10.1136/esmoopen-2019-000524. eCollection 2019.
Since the discovery of anaplastic lymphocyte kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) and subsequent development of increasingly effective and central nervous system (CNS)-penetrant first-generation, second-generation and third-generation ALK tyrosine kinase inhibitors (TKIs), the landscape of resistance mechanisms and treatment decisions has become increasingly complex. Tissue and/or plasma-based molecular tests can identify not only the rearrangement proper but also common resistance mechanisms to guide decision-making for further lines of treatment. However, frequently encountered questions exist regarding how to diagnosis ALK rearrangement, how to select a first-line ALK TKI, how to diagnose and manage ALK TKI resistance, how to control CNS disease and how to handle failure of ALK inhibition. Herein, we attempt to answer these questions through the evidence-based interpretation of studies on ALK-rearranged NSCLC combined with experience gained from our institution. The authors also propose a therapeutic algorithm for the management of this complex and highly treatable disease to assist clinicians globally in the treatment of patients with ALK-positive NSCLC.
自从在非小细胞肺癌（NSCLC）中发现间变性淋巴瘤激酶（ALK）重排以及随后开发出越来越有效且能穿透中枢神经系统（CNS）的第一代、第二代和第三代ALK酪氨酸激酶抑制剂（TKIs）以来，耐药机制和治疗决策的情况变得越来越复杂。基于组织和/或血浆的分子检测不仅可以识别ALK重排本身，还能识别常见的耐药机制，以指导后续治疗方案的决策。然而，关于如何诊断ALK重排、如何选择一线ALK TKI、如何诊断和处理ALK TKI耐药、如何控制CNS疾病以及如何应对ALK抑制失败等问题经常出现。在此，我们试图通过对ALK重排NSCLC研究的循证解读，并结合我们机构积累的经验来回答这些问题。作者还提出了一种针对这种复杂且高度可治疗疾病的治疗算法，以协助全球临床医生治疗ALK阳性NSCLC患者。
