Fatigue with vascular endothelial growth factor receptor tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors in patients with renal cell carcinoma (RCC) and other malignancies: A meta-analysis of randomized clinical trials.

A trial-level meta-analysis of randomized phase II/III controlled trials in renal cell carcinoma (RCC) and other malignancies was conducted to systematically determine the relative risk (RR) of fatigue, a common side effect associated with single agent therapy with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) and mammalian target of rapamycin inhibitors (mTORi). The RR of all grade fatigue and high grade fatigue in 7304 patients from 19 trials was 1.35 (95% CI 1.22-1.49, p<0.001) and 1.33 (95% CI 0.97-1.82, p=0.08), respectively in patients receiving VEGFR TKIs or mTORi. The summary incidence of all grade and high grade fatigue in the drug arm was 38.2% (95% CI 31.8-45.1) and 4.0% (95% CI 2.8-5.7), respectively. The type of drug (VEGFR TKI vs. mTORi), line of therapy, age, type of tumor (RCC vs. others) and median duration of therapy did not affect the risk of all-grade fatigue.