Pharmacological and clinical properties of lorlatinib in the treatment ofALK-rearranged advanced non-small cell lung cancer
Pharmacological and clinical properties of lorlatinib in the treatment ofALK-rearranged advanced non-small cell lung cancer
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DOI：
10.1080/14656566.2020.1774552
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发表时间：
2020-06-09
影响因子：
3.2
通讯作者：
Sangha, Randeep
中科院分区：
文献类型：
--
作者：
Eldarsa, Haidar;Abdel-Rahman, Omar;Sangha, Randeep
简介 大约 3-7% 的晚期非小细胞肺癌 (NSCLC) 是由间变性淋巴瘤激酶 (ALK) 重排引起的。 Crizotinib、ceritinib、alectinib 和 brigatinib 是活性 ALK 抑制剂 (ALKi)，用于治疗这种癌基因驱动的 NSCLC 亚型。随着时间的推移，ALKi 会出现耐药性，并且新的治疗方法正在开发中。 Lorlatinib 是一种有效的第三代 ALKi，能够克服第一代或第二代 ALKi 产生的耐药突变。涵盖的领域 在本文中，作者回顾了劳拉替尼的作用机制、药代动力学、药效学、临床疗效和安全性，并提出了他们对该药物的未来展望。专家评论 Lorlatinib 是一种有效的 ALK 和 ROS-1 抑制剂，还具有对抗许多获得性 ALK 耐药突变的活性。临床试验表明，lorlatinib 在 ALK 重排晚期 NSCLC 中具有强大的全身和颅内抗肿瘤活性。劳拉替尼的不良事件是独特且可控的。这些包括低胆固醇血症、高甘油三酯血症、水肿、认知影响、体重增加和腹泻。随着 ALKi 的最佳测序正在进行进一步研究，劳拉替尼将在 ALK 重排 NSCLC 的治疗中发挥越来越重要的作用。
Introduction Approximately 3-7% of advanced non-small cell lung cancers (NSCLC) are driven by an anaplastic lymphoma kinase (ALK) rearrangement. Crizotinib, ceritinib, alectinib, and brigatinib are activeALKinhibitors (ALKi) used to treat this oncogene-driven subset of NSCLC. Resistance occurs with time to ALKi and new therapeutics are being developed. Lorlatinib is an efficacious third-generation ALKi with an ability to overcome resistance mutations that develop with first- or second-generation ALKi. Areas covered Herein, the authors review the mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of lorlatinib and provide their future perspectives on this drug. Expert commentary Lorlatinib is a potentALKandROS-1inhibitor that also has activity against many acquiredALKresistance mutations. Clinical trials show the robust systemic and intracranial anti-tumor activity of lorlatinib inALKrearranged advanced NSCLC. Adverse events of lorlatinib are unique and manageable. These include hypocholesteremia, hypertriglyceridemia, edema, cognitive effects, weight gain, and diarrhea. Loratinib will play an increasing role in the management ofALK-rearranged NSCLC with the optimal sequencing of ALKi undergoing further research.