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Targeted Oncology
Published in: Targeted Oncology 5/2018

Open Access 01-10-2018 | Original Research Article

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

Authors: Annelieke E. C. A. B. Willemsen, Lioe-Fee de Geus-Oei, Maaike de Boer, Jolien Tol, Yvonne Kamm, Paul C. de Jong, Marianne A. Jonker, Allert H. Vos, Willem Grootjans, Johannes W. B. de Groot, Sasja F. Mulder, Erik H. J. G. Aarntzen, Winald R. Gerritsen, Carla M. L. van Herpen, Nielka P. van Erp

Published in: Targeted Oncology | Issue 5/2018

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Abstract

Background

Treating breast cancer patients with everolimus and exemestane can be challenging due to toxicity and suboptimal treatment responses.

Objective

We investigated whether everolimus exposure and early metabolic response are predictors for toxicity and effectiveness in these patients.

Patients and Methods

We performed pharmacokinetic assessments 14 and 35 days after starting treatment. [18F]fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) was performed at baseline, and 14 and 35 days after the start of the therapy. We recorded toxicity, defined as dose interventions within 3 months, and progression-free survival (PFS).

Results

Among 44 evaluable patients, the geometric mean (GM) Ctrough was higher in patients with toxicity compared to patients without (17.4 versus 12.3 μg/L (p = 0.02)). The optimal cut-off value to predict toxicity was Ctrough > 19.2 μg/L. GM Ctrough of patients with and without progressive disease (PD) within 3 months was not significantly different (12.0 versus 15.2 μg/L (p = 0.118)). In 28 evaluable patients, PD within 3 months 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 90 days versus 411 days, respectively (p = 0.0013) and more frequently had PD within 3 months: 70 vs 11%, respectively.

Conclusions

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.
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Metadata
Title
Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane
Authors
Annelieke E. C. A. B. Willemsen
Lioe-Fee de Geus-Oei
Maaike de Boer
Jolien Tol
Yvonne Kamm
Paul C. de Jong
Marianne A. Jonker
Allert H. Vos
Willem Grootjans
Johannes W. B. de Groot
Sasja F. Mulder
Erik H. J. G. Aarntzen
Winald R. Gerritsen
Carla M. L. van Herpen
Nielka P. van Erp
Publication date
01-10-2018
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 5/2018
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-018-0596-8

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