PMID- 37334877 OWN - NLM STAT- MEDLINE DCOM- 20230901 LR - 20230902 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 12 IP - 15 DP - 2023 Aug TI - A Bayesian network meta-analysis of ALK inhibitor treatments in patients with ALK-positive non-small cell lung cancer. PG - 15983-15997 LID - 10.1002/cam4.6241 [doi] AB - OBJECTIVE: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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. CI - (c) 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Zheng, Bei AU - Zheng B AUID- ORCID: 0000-0003-0575-1607 AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Jiang, Hong AU - Jiang H AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Yang, Wenjuan AU - Yang W AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Li, Ying AU - Li Y AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Liang, Bingqing AU - Liang B AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Zhu, Jun AU - Zhu J AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Chen, Nanmei AU - Chen N AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Chen, Miao AU - Chen M AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Zhang, Meiling AU - Zhang M AUID- ORCID: 0000-0002-1023-8827 AD - Department of Pharmacy, Tongde Hospital Zhejiang Province, Hangzhou, China. AD - Department of Pharmacy, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20230619 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - K418KG2GET (ceritinib) RN - OSP71S83EU (lorlatinib) RN - HYW8DB273J (brigatinib) RN - 53AH36668S (Crizotinib) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Carbazoles) SB - IM MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics MH - Crizotinib/therapeutic use MH - *Lung Neoplasms/drug therapy/genetics MH - Network Meta-Analysis MH - Bayes Theorem MH - Anaplastic Lymphoma Kinase/genetics MH - Protein Kinase Inhibitors/adverse effects MH - *Brain Neoplasms/secondary MH - Carbazoles/therapeutic use PMC - PMC10469807 OTO - NOTNLM OT - ALK inhibitor OT - Bayesian OT - network meta-analysis OT - non-small cell lung cancer COIS- No authors declared a conflict of interest. EDAT- 2023/06/19 13:08 MHDA- 2023/09/01 06:43 PMCR- 2023/06/19 CRDT- 2023/06/19 06:53 PHST- 2023/03/28 00:00 [revised] PHST- 2022/08/25 00:00 [received] PHST- 2023/06/02 00:00 [accepted] PHST- 2023/09/01 06:43 [medline] PHST- 2023/06/19 13:08 [pubmed] PHST- 2023/06/19 06:53 [entrez] PHST- 2023/06/19 00:00 [pmc-release] AID - CAM46241 [pii] AID - 10.1002/cam4.6241 [doi] PST - ppublish SO - Cancer Med. 2023 Aug;12(15):15983-15997. doi: 10.1002/cam4.6241. Epub 2023 Jun 19.