Incidence and risk of fatigue in cancer patients treated with MET inhibitors: A systematic review and meta-analysis

BACKGROUND: The N-methyl-N′-nitroso-guanidine human osteosarcoma transforming gene (MET) inhibitors show a surprising survival benefit in the treatment of numerous tumors especially in MET-high tumor. Besides their impressive efficacy, fatigue reduced by MET inhibitors is still the safety issue during treatment. Thus, an understanding of this risk in the context of expanding MET-inhibitors use is an important cost and patient safety issue. METHODS: We searched PubMed, Embase, and the Cochrane Library databases for relevant studies up to October 2017. Eligibility criteria included phase II/III trials of MET inhibitors that reported adequate safety profiles of fatigue. The principal summary measures were incidence and relative risk (RR) of all-grade (grade 1–4) and high-grade (grade 3–4) fatigue, respectively. Random-effects model was applied to consider within-study and between-study variation. RESULTS: A total of 5028 patients from 17 clinical trials were identified. The results revealed that the incidences of MET inhibitors-associated all-grade and high-grade fatigue were 41.9% and 9.6%, respectively. The RR of high-grade fatigue was (RR = 1.37; 95% confidence interval, 1.14–1.66; P = .0009), whereas the RR of all-grade fatigue was (RR = 1.02; 95% confidence interval, 0.91–1.15; P = .71). CONCLUSION: Our meta-analysis has demonstrated that MET inhibitors-based treatment is associated with an increased risk of high-grade fatigue compared with control.