Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China.
Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China.
Cancer Med. 2023 Aug;12(15):15983-15997. doi: 10.1002/cam4.6241. Epub 2023 Jun 19.
To date, no direct comparisons have compared the effectiveness of all ALK inhibitors (ALKis) against ALK-positive non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the efficacy and safety of ALKis in ALK-positive NSCLC.
The effectiveness of ALKis was evaluated by assessing progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and PFS with baseline brain metastasis (BM). The serious adverse events (SAEs: Grade ≥ 3) and adverse events (AEs) leading to discontinuation were pooled to evaluate safety. We conducted an indirect treatment comparison between all ALKis by using a Bayesian model.
Twelve eligible trials including seven treatments were identified. All of the ALKis improved PFS and ORR relative to chemotherapy. Consistent with alectinib, brigatinib, lorlatinib, and ensartinib showed significant differences versus crizotinib and ceritinib. Lorlatinib seemed to prolong PFS compared with alectinib (0.64, 0.37 to 1.07), brigatinib (0.56, 0.3 to 1.05), and ensartinib (0.53, 0.28 to 1.02). No significant difference was found among them in OS except for alectinib versus crizotinib. Moreover, alectinib was significantly more effective than crizotinib (1.54, 1.02 to 2.5) in achieving the best ORR. Subgroup analyses based on BM indicated that PFS was dramatically lengthened by lorlatinib. Compared with other ALKis, alectinib notably reduced the rate of SAEs. There was no striking difference between discontinuation for AEs, except for ceritinib versus crizotinib. The ranking of validity showed that lorlatinib had the longest PFS (98.32%) and PFS with BM (85.84%) and the highest ORR (77.01%). The rank of probabilities showed that alectinib had the potentially best safety in terms of SAEs (97.85%), and ceritinib had less discontinuation (95.45%).
Alectinib was the first choice for patients with ALK-positive NSCLC and even for those with BM, whereas lorlatinib was the second choice. Long-term follow-up and prospective studies are warranted to compare ALKis and to verify our conclusions directly.
迄今为止，尚无直接比较研究比较过所有间变性淋巴瘤激酶抑制剂（ALKis）对间变性淋巴瘤激酶阳性非小细胞肺癌（NSCLC）的疗效。本研究旨在探讨ALKis 治疗间变性淋巴瘤激酶阳性 NSCLC 的疗效和安全性。
通过评估无进展生存期（PFS）、总生存期（OS）、总缓解率（ORR）以及基线脑转移（BM）的 PFS，评估 ALKi 的疗效。将严重不良事件（SAE：≥3 级）和导致停药的不良事件（AE）进行汇总，以评估安全性。通过贝叶斯模型对所有 ALKi 进行间接治疗比较。
纳入了 12 项符合条件的试验，包括 7 种治疗方法。所有 ALKi 与化疗相比均改善了 PFS 和 ORR。与克唑替尼和塞瑞替尼相比，阿来替尼、布加替尼、劳拉替尼和恩沙替尼均显示出显著差异。与阿来替尼、布加替尼和恩沙替尼相比，劳拉替尼似乎延长了 PFS（0.64，0.37 至 1.07）。除阿来替尼与克唑替尼外，OS 无显著差异。此外，阿来替尼在获得最佳 ORR 方面比克唑替尼更有效（1.54，1.02 至 2.5）。基于 BM 的亚组分析表明，洛拉替尼显著延长了 PFS。与其他 ALKi 相比，阿来替尼显著降低了 SAE 发生率。除塞瑞替尼与克唑替尼外，AE 导致停药率无显著差异。有效性排名显示，劳拉替尼具有最长的 PFS（98.32%）和 PFS 与 BM（85.84%）和最高的 ORR（77.01%）。概率排名显示，在 SAE 方面，阿来替尼可能具有最佳安全性（97.85%），而塞瑞替尼停药率较低（95.45%）。
阿来替尼是间变性淋巴瘤激酶阳性 NSCLC 患者的首选药物，甚至对有 BM 的患者也是如此，而劳拉替尼是第二选择。需要进行长期随访和前瞻性研究来比较 ALKi 并直接验证我们的结论。
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