Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane.

Abstract

Treating breast cancer patients with everolimus and exemestane can be challenging due to toxicity and suboptimal treatment responses. We investigated whether everolimus exposure and early metabolic response are predictors for toxicity and effectiveness in these patients. We performed pharmacokinetic assessments 14 and 35days after starting treatment. [18F]fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) was performed at baseline, and 14 and 35days after the start of the therapy. We recorded toxicity, defined as dose interventions within 3months, and progression-free survival (PFS). Among 44 evaluable patients, the geometric mean (GM) Ctrough was higher in patients with toxicity compared to patients without (17.4 versus 12.3μg/L (p = 0.02)). The optimal cut-off value to predict toxicity was Ctrough > 19.2μg/L. GM Ctrough of patients with and without progressive disease (PD) within 3months was not significantly different (12.0 versus 15.2μg/L (p = 0.118)). In 28 evaluable patients, PD within 3months could best be predicted using the percentage decrease in peak standardized uptake value normalized by lean body mass of the lesion with highest FDG uptake (SULpeak high) at day 14. Patients with <11% versus >11% decrease in SULpeak high at day 14 had a median PFS of 90days versus 411days, respectively (p = 0.0013) and more frequently had PD within 3months: 70 vs 11%, respectively. Our results show that everolimus toxicity is related to everolimus Ctrough. No relation was observed between everolimus exposure and treatment effectiveness. An early FDG-PET can identify patients at high risk of nonresponse. These results warrant further validation. Clinicaltrials.gov identifier: NCT01948960.