多种下一代 ALK TKI 可作为 ALK 阳性 NSCLC 的一线选择，其中艾来替尼和劳拉替尼通常是首选。然而，尚未对它们进行直接比较，因此无法选出获胜者。我们对两项 3 期关键临床试验进行了分析性“非比较”评估，显示艾乐替尼 (ALEX) 和劳拉替尼 (CROWN) 与克唑替尼相比具有优越性。总体而言，除了脑转移瘤的选择和评估之外，这两项研究在研究设计和患者特征方面非常相似。根据研究者和 BICR 的说法，PFS 风险比在数值上有利于 lorlatinib。值得注意的是，劳拉替尼 (lorlatinib) 的 3 年 PFS 率 (64%) 高于艾乐替尼 (alectinib) (46.4%)。尽管缓解率和总体颅内缓解相似，但劳拉替尼的颅内完全缓解率较高，12 个月时中枢神经系统疾病进展的累积发生风险艾乐替尼为 9.4%，劳拉替尼为 2.8%。劳拉替尼的特殊毒性与血脂谱改变、外周水肿和认知影响有关，与克唑替尼相比，不会影响心血管风险，也不会损害生活质量。此外，艾乐替尼组因不良事件而永久停止治疗的比率 (26%) 高于劳拉替尼组 (7%)。总之，尽管两种药物的 OS 数据不成熟，但劳拉替尼的疗效似乎高于艾乐替尼，同时保持了可控的毒性特征。

Various next-generation ALK TKIs are available as first-line options for ALK-positive NSCLC, with alectinib and lorlatinib being commonly preferred. However, no direct comparison between them has been conducted, making it impossible to pick a winner. We performed an analytic, 'non-comparative' assessment of the two phase 3 pivotal clinical trials showing superiority of alectinib (ALEX) and lorlatinib (CROWN) in comparison to crizotinib. Overall, the two studies were very similar in the study design and patient characteristics, with the exception of the selection and evaluation of brain metastases. PFS hazard ratios numerically favored lorlatinib, both according to the investigator and to BICR. Notably, the 3-year PFS rate was numerically higher with lorlatinib (64%) than with alectinib (46.4%). Despite similar response rates and overall intracranial response, the rate of complete intracranial response was higher with lorlatinib, with a cumulative incidence risk of CNS disease progression at 12 months of 9.4% with alectinib and 2.8% with lorlatinib. The peculiar toxicities of lorlatinib were related to lipidic profile alterations, peripheral oedema and cognitive effects, with no impact on cardiovascular risk nor impairment in quality of life versus crizotinib. Furthermore, the rate of permanent treatment discontinuation due to adverse events was numerically higher with alectinib (26%) than with lorlatinib (7%). In conclusion, despite the immature OS data for both drugs, the efficacy of lorlatinib appears higher than alectinib while maintaining a manageable toxicity profile.