First-line treatments for patients with advanced ALK gene rearrangements in NSCLC: a systematic review and network meta-analysis. Issue 11 (November 2022)

• Record Type: Journal Article
• Authors: Tao, Jiahao; Zheng, Chuangjie; Zhang, Cuifen; Zhou, Ling; Liu, Zeyu; Zhou, Yanqun; Huang, Xuewu; Lin, Lizhu; Zhai, Linzhu
• Is Part Of: Journal of international medical research. Volume 50:Issue 11(2022)
• Publication Date: 2022-11
• Subjects: Non-small cell lung cancer -- anaplastic lymphoma kinase -- first-line therapy -- lorlatinib -- ALK inhibitors -- brigatinib; Medicine -- Periodicals; Pharmacology -- Periodicals; 610.5
• DOI: 10.1177/03000605221132703
• Languages: English
• ISSNs: 0300-0605

Abstract

Objective: To conduct a network meta-analysis of randomised controlled trials to determine the optimal clinical choice of first-line therapy for patients with ALK receptor tyrosine kinase ( ALK ) gene rearrangement non-small cell lung cancer (NSCLC). Methods: Clinical trials in patients with histologically confirmed ALK gene rearrangement NSCLC, that included ALK inhibitors as first-line therapy, were identified using database searches. A Bayesian network meta-analysis was conducted to calculate the efficacy and safety of the included first-line treatments. Results: Nine trials with 2, 407 patients were included for analyses. Lorlatinib was better than brigatinib for progression-free survival (PFS) (hazard ratio 0.79, 95% confidence interval 0.63, 0.98). In subgroup analyses, lorlatinib exhibited the highest probability of best PFS ranking in patients with or without baseline brain metastases (38% and 80%, respectively); brigatinib had the highest probability of best PFS ranking among Asian patients (47%). Alectinib offered the highest survival advantage (57% probability), while lorlatinib was likely to be the best treatment for an objective response (41% probability). Alectinib displayed the highest probability of being ranked lowest for grade ≥3 adverse events (86%). Conclusions: Lorlatinib was associated with the best PFS overall, and was suitable for patients with or without brain metastases. Brigatinib was associated with the best PFS in Asian patients.