Correlation between ALK+ non-small cell lung cancer targeted therapy and thrombosis: a systematic review and network meta-analysis

ObjectiveThe main adjuvant therapies for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer include ALK tyrosine kinase inhibitors (TKI) and chemotherapy. We aimed to compare differences in the incidence of thromboembolism (TE) among different treatment options.DesignUsing a systematic review and Bayesian network meta-analysis (NMA).Data sourcesWe searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Web of Science databases before 10 June 2023.Eligibility criteriaWe included published randomised controlled trials (RCT) involving comparisons of treatments between chemotherapy and ALK-TKI drugs.Data extraction and synthesisAssessed risk bias with Cochrane tool. Conducted NMA with GEMTC in R, we evaluate the model fit using the deviation information criteria. Estimated posterior distribution using Markov Chain Monte Carlo, 4 chains, 10 fine-tuned iterations, 10 000 iterations per chain, total 50 000 iterations. Monitored potential scale reduction factor for convergence. And checked convergence with Gelman-Rubin statistics and trace plot. Provided surface under the cumulative ranking, lower values indicate less TE event probability.ResultsAnalysis of eight RCTs showed that, compared with that for crizotinib, there was a lower risk of total TE with chemotherapy (OR, 0.28; 95% credible intervals (CrI) 0.11 to 0.63), brigatinib (OR 0.31; 95% CrI 0.11 to 0.79) and ceritinib (OR 0.13; 95% CrI 0.03 to 0.45). In addition, analysis of venous TE (VTE) showed similar results, with a lower occurrence for chemotherapy (OR 0.27; 95% CrI 0.1 to 0.62), brigatinib (OR 0.18; 95% CrI 0.04 to 0.6) and ceritinib (OR 0.1; 95% CrI 0.02 to 0.43) compared with that for crizotinib. There were no significant differences in the occurrence of arterial TE among the different treatment options.ConclusionCompared with chemotherapy, alectinib, lorlatinib, brigatinib and ceritinib, crizotinib significantly increased the risk of TE and VTE.PROSPERO registration numberCRD42023373307.