Zia Victor, Lengyel Csongor György, Tajima Carla Chizuru, de Mello Ramon Andrade
Post-graduation Program in Translational Medicine, University Federal of São Paulo, São Paulo, Brazil.
Department of Head and Neck Surgery, National Institute of Oncology Hungary, Budapest, Hungary.
Transl Lung Cancer Res. 2023 Jul 31;12(7):1563-1574. doi: 10.21037/tlcr-22-619. Epub 2023 Jul 4.
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.
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.
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.
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.
在过去几年中，非小细胞肺癌（NSCLC）的治疗格局发生了显著变化。靶向药物和分子诊断技术一直在快速协同发展。本叙述性综述探讨了间变性淋巴瘤激酶（ALK）靶向治疗从ALK蛋白的发现、分子检测、当前临床试验数据到未来前景的演变。由于关于肺癌的证据日益增多，大多数肿瘤学家需要时间在日常实践中应用这些数据。
我们开展了一项叙述性综述，为ALK改变的NSCLC患者的临床决策提供最新帮助。2022年，作者查阅了PubMed上发表的关键随机3期试验结果。
ALK抑制剂的研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）以及令人印象深刻的“脑控制”效果。布加替尼为基线有脑转移的患者带来了生存获益（HR 0.43，95% CI：0.21 - 0.89），劳拉替尼的颅内缓解率为82%，其中71%为颅内完全缓解。精准医学是新的范式，从进行广泛的基因检测以进行诊断，到个体化靶向治疗或不同靶向药物的联合应用。
未来，在一线以及每次病情进展后进行广泛的分子检测应成为标准治疗，以检测出现的耐药机制。更长的PFS将在未来几十年把一种致命疾病基本上转变为一种几乎是慢性病的状态。治疗顺序将是患者生存的基石，液体活检可能会取代组织活检。
