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

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

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. [F-18]fluorodeoxyglucose-positron emission tomography (F-18-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) C-trough was higher in patients with toxicity compared to patients without (17.4 versus 12.3 mu/L (p = 0.02)). The optimal cut-off value to predict toxicity was C-trough > 19.2 mu/L. GM C-trough of patients with and without progressive disease (PD) within 3 months was not significantly different (12.0 versus 15.2 mu/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% 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 C-trough. 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.

Original languageEnglish
Pages (from-to)641-648
Number of pages8
JournalTargeted Oncology
Volume13
Issue number5
DOIs
Publication statusPublished - Oct 2018

Keywords

  • MTOR INHIBITOR EVEROLIMUS
  • SOLID TUMORS
  • PHASE-I
  • ENDOCRINE MONOTHERAPY
  • MAMMALIAN TARGET
  • PLUS EXEMESTANE
  • EFFICACY
  • SAFETY
  • PET
  • CHEMOTHERAPY

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