■非小细胞肺癌(NSCLC)的治疗前景在过去几年中已经有了很大的发展。靶向药物和分子诊断已经快速发展。这篇叙述性综述从发现ALK蛋白,探讨了间变性淋巴瘤激酶(ALK)靶向治疗的演变。分子测试,目前的临床试验数据和未来的观点。由于肺癌的证据每天都在增加,大多数肿瘤学家需要时间在日常实践中实施数据。
■我们进行了叙述性综述,为ALK改变的NSCLC患者的临床决策提供最新帮助。2022年,作者回顾了PubMed发表的关键随机3期试验结果。
ALK抑制剂的开发是一场仍在进行的革命;第二代和第三代ALK抑制剂提供了超过30个月的无进展生存期(PFS)和令人印象深刻的“脑控制”。Brigatinib为基线脑转移患者提供了生存益处(HR0.43,95%CI:0.21-0.89),洛拉替尼的颅内反应率为82%,71%的颅内完全缓解.个性化医疗是新的范式,从进行广泛的遗传小组诊断到单独的靶向治疗或不同靶向药物的组合。
■在未来,进行宽分子面板应该是在前线和每次进展后检测出现的耐药机制的标准护理。在接下来的几十年中,更长的PFS将使致命的疾病转化为几乎慢性的疾病。治疗测序将是患者生存的基石,和液体活检可以代替组织活检。
UNASSIGNED: The therapeutic landscape for non-small cell lung cancer (NSCLC) has evolved considerably in the last few years. The targeted drugs and molecular diagnostics have been developed together at a fast pace. This narrative review explores the evolution of anaplastic lymphoma kinase (ALK) targeting therapies from discovering the ALK protein, molecular tests, present clinical trial data and future perspectives. Since the body of evidence on lung cancer is growing daily, most oncologists need time to implement data in their daily practice.
UNASSIGNED: We developed a narrative review to provide up-to-date help in the clinical decision-making of ALK-altered NSCLC patients. In 2022, the authors reviewed PubMed\'s published pivotal randomized Phase 3 trial results.
UNASSIGNED: The development of ALK inhibitors was a revolution that is still ongoing; second and third-generation ALK inhibitors provided more than 30 months of progression-free survival (PFS) and impressive \"brain-control\". Brigatinib provided a survival benefit for patients with baseline brain metastases (HR 0.43, 95% CI: 0.21-0.89), and Lorlatinib demonstrated intracranial response rates of 82%, with 71% of complete intracranial responses. Personalized medicine is the new paradigm, from performing broad genetic panels for diagnosis to individual targeted therapy or combinations of different targeted agents.
UNASSIGNED: In the future, performing broad molecular panels should be the standard of care in the front line and after each progression to detect arising resistance mechanisms. Longer PFS will substantially convert a deadly condition into an almost chronic disease in the following decades. Treatment sequencing will be the cornerstone for patient survival, and liquid biopsies may replace tissue biopsies.