asco@alo33:161827 JSONTXT

Background: The mTOR mammalian target of rapamycin inhibitor everolimus, a targeted agent used idely in cancer patients, is often discontinued due to serious adverse events. It is challenging to differentiate beteen adverse events related and unrelated to everolimus therapy, as these effects may be due to the drug itself, or confounding factors such as the underlying cancer, comorbidities, and concurrent medications. To assess the scope of this issue, a meta-analysis of randomized controlled trials as performed to examine the risk of everolimus discontinuation due to unrelated adverse events. Methods: A PubMed search as performed to identify all randomized controlled clinical trials here everolimus as compared to placebo ith or ithout concurrent therapies in cancer patients. Eligible clinical trials reported a discontinuation rate due to adverse events for the everolimus group related and unrelated to everolimus and the placebo control group unrelated to everolimus . A random- or fixed effects model as used to determine summary incidences, relative risks and 95 percent confidence intervals. Results: A total of 15 RCTs ere eligible for analysis, including a total of 5,631 patients everolimus: n = 3366, control: n = 2265 . The incidences of everolimus discontinuation as 12.3 percent 95 percent CI: 9.5-15.8 percent due to all adverse events and 4.7 percent 95 percent CI: 3.1-7.0 percent due to unrelated adverse events. Adverse events unrelated to everolimus contributed to discontinuation at a relative risk of 0.39 95 percent CI: 0.28-0.54 . Subgroup analysis shoed discontinuation risk due to unrelated adverse events varied significantly ith cancer types P lt 0.001 . The loest risk as seen in renal cell cancer RR = 0.12, 95 percent CI: 0.03-0.46 , and highest seen in angiomyolipoma associated ith tuberous sclerosis RR = 4.0, 95 percent CI: 0.75-21.2 . Risk of discontinuation due to unrelated adverse events did not vary significantly ith dose P = 0.84 or its combination ith other agents P = 0.49 . Conclusions: There is a substantial risk of everolimus discontinuation due to unrelated adverse events in cancer treatment. Serious efforts should be made to differentiate beteen related and unrelated adverse events before stopping therapy.,J Clin Oncol 34, 2016 suppl; abstr e14020 ,Publication Only Developmental Therapeutics and Translational ResearchClinical Pharmacology and Experimental Therapeutics