Wang Lida, Sheng Zhixin, Zhang Junying, Song Jiwu, Teng Lili, Liu Liping, Li Qianpeng, Wang Baohong, Li Bin
Department of E.N.T, Weifang People's Hospital, Weifang, China.
Department of Hematology, Weifang People's Hospital, Weifang, China.
J Chemother. 2022 Apr;34(2):87-96. doi: 10.1080/1120009X.2021.1937782. Epub 2021 Jun 17.
Because of lacking of head-to-head comparison among lorlatinib, alectinib and brigatinib for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced non-small-cell lung cancer (NSCLC), the optimal option for these patients still remains undefined. We searched published reports that described the activity and safety of those novel ALK inhibitors (lorlatinib, alectinib and brigatinib) for ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced NSCLC. Five randomized controlled trials were identified, covering 1111 subjects. In the network meta-analysis, lorlatinib seemed to prolong progression free survival than brigatinib (Hazard Ratio: 0.57, = 0.03) and alectinib (Hazard ratio: 0.65, = 0.05) for previously untreated patients with ALK-positive advanced NSCLC as assessed by the independent review committee. Meanwhile, lorlatinib significantly improved significant progression free survival than brigatinib (Hazard ratio: 0.57, = 0.03) and alectinib (Hazard ratio: 0.59, = 0.03) for ALK inhibitor-naive patients. Among lorlatinib, alectinib, brigatinib, and crizotinib, lorlatinib had the highest probability to reach the best overall confirmed response rates (probability of 48%) and intracranial confirmed response rates (probability of 44%). No significant difference was found among them in overall survival and adverse events analysis. In terms of progression free survival, our results indicated that lorlatinib was the best treatment choice for patients with ALK inhibitor-naive or untreated (ALK inhibitor-naive and chemotherapy-naive) ALK-positive advanced NSCLC. The future head-to-head trials assessing the relative efficacy of lorlatinib, alectinib and brigatinib were warranted.
由于针对初治或未接受过治疗（初治ALK且未接受过化疗）的ALK阳性晚期非小细胞肺癌（NSCLC）患者，劳拉替尼、阿来替尼和布加替尼之间缺乏直接对比，这些患者的最佳治疗选择仍不明确。我们检索了已发表的报告，这些报告描述了那些新型ALK抑制剂（劳拉替尼、阿来替尼和布加替尼）用于初治或未接受过治疗（初治ALK且未接受过化疗）的ALK阳性晚期NSCLC的活性和安全性。共确定了5项随机对照试验，涵盖1111名受试者。在网状Meta分析中，根据独立审查委员会的评估，对于既往未接受过治疗的ALK阳性晚期NSCLC患者，劳拉替尼似乎比布加替尼（风险比：0.57，P = 0.03）和阿来替尼（风险比：0.65，P = 0.05）更能延长无进展生存期。同时，对于初治ALK患者，劳拉替尼比布加替尼（风险比：0.57，P = 0.03）和阿来替尼（风险比：0.59，P = 0.03）显著改善了无进展生存期。在劳拉替尼、阿来替尼、布加替尼和克唑替尼中，劳拉替尼达到最佳总体确认缓解率（概率为48%）和颅内确认缓解率（概率为44%）的可能性最高。在总生存期和不良事件分析中，它们之间未发现显著差异。就无进展生存期而言，我们的结果表明，劳拉替尼是初治或未接受过治疗（初治ALK且未接受过化疗）的ALK阳性晚期NSCLC患者的最佳治疗选择。未来有必要开展评估劳拉替尼、阿来替尼和布加替尼相对疗效的直接对比试验。
