Therapeutic drug monitoring of Everolimus in oncology: evidences and perspectives.

Everolimus is a mammalian target of rapamycine (m-TOR) inhibitor that has been approved for the treatment of hormone receptor-positive advanced breast cancer, metastatic renal cancer and neuroendocrine tumors. While therapeutic drug monitoring (TDM) of everolimus is well established in the transplantation field, it is not currently performed in oncology. The last consensus conference about the TDM of everolimus states that for the use of everolimus in oncology "Further studies are required to determine the clinical utility of TDM for everolimus in oncology settings". In this review, the authors will discuss the current evidences and perspectives, based on observational studies available, in favor of the TDM of everolimus in oncology focusing on (i) the management of everolimus in routine practice, (ii) the prerequisites for TDM of everolimus in oncology, (iii) the pharmacodynamics (including a description of the biomarker of resistance and mutations in m-TOR) and (iv) a general outlook.

• Publication year

  2019

• Venue

  Therapeutic Drug Monitoring

• Publication date

  2019-10-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1097/FTD.0000000000000628PMID 30913132
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A pharmacological rationale for improved everolimus dosing in oncology and transplant patients

  2018cited by this paper
• Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane

  2018cited by this paper
• Everolimus (EVE) exposure as a predictor of toxicity (Tox) in renal cell cancer (RCC) patients (Pts) in the adjuvant setting: Results of a pharmacokinetic analysis for SWOG S0931 (EVEREST), a phase III study (NCT01120249).

  2017cited by this paper
• Everolimus in advanced, progressive, well‐differentiated, non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis

  2017cited by this paper
• Genomic Biomarkers of a Randomized Trial Comparing First-line Everolimus and Sunitinib in Patients with Metastatic Renal Cell Carcinoma.

  2017cited by this paper
• Towards therapeutic drug monitoring of everolimus in cancer? Results of an exploratory study of exposure‐effect relationship

  2017cited by this paper
• Pharmacogenetics of immunosuppressants: State of the art and clinical implementation - recommendations from the French National Network of Pharmacogenetics (RNPGx).

  2017cited by this paper
• Pharmacokinetic Optimization of Everolimus Dosing in Oncology: A Randomized Crossover Trial

  2017cited by this paper
• Correlation between PIK3CA mutations in cell-free DNA and everolimus efficacy in HR+, HER2− advanced breast cancer: results from BOLERO-2

  2017cited by this paper
• New challenges and promises in solid organ transplantation pharmacogenetics: the genetic variability of proteins involved in the pharmacodynamics of immunosuppressive drugs.

  2016cited by this paper
• Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells

  2016cited by this paper
• Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

  2016cited by this paper
• Endocrine resistance in hormone-responsive breast cancer: mechanisms and therapeutic strategies.

  2016cited by this paper
• Population Pharmacokinetics of Everolimus in Relation to Clinical Outcomes in Patients With Advanced Renal Cell Carcinoma

  2016cited by this paper
• Therapeutic Drug Monitoring of Everolimus: A Consensus Report

  2016cited by this paper
• Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study.

  2016cited by this paper
• Everolimus for patients with metastatic renal cell carcinoma refractory to anti-VEGF therapy: results of a pooled analysis of non-interventional studies.

  2015cited by this paper
• Real-world study of everolimus in advanced progressive neuroendocrine tumors.

  2015cited by this paper
• Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.

  2015cited by this paper
• Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.

  2015cited by this paper
• Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial.

  2015cited by this paper
• Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer.

  2015cited by this paper
• Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer.

  2015cited by this paper
• Erratum: Real-world study of everolimus in advanced progressive neuroendocrine tumors (The Oncologist, (2014) 19, (966-974), 10.1634/theoncologist.2014-0037)

  2015cited by this paper
• Relationship between everolimus exposure and safety and efficacy: meta-analysis of clinical trials in oncology.

  2014cited by this paper
• Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma

  2014cited by this paper
• Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2

  2014cited by this paper
• Tumor Genetic Analyses of Patients with Metastatic Renal Cell Carcinoma and Extended Benefit from mTOR Inhibitor Therapy

  2014cited by this paper
• Adverse event management in patients with advanced cancer receiving oral everolimus: focus on breast cancer.

  2014cited by this paper
• Therapeutic drug monitoring in cancer--are we missing a trick?

  2014cited by this paper
• Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients with metastatic renal cell carcinoma

  2014cited by this paper
• FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer

  2013cited by this paper
• Everolimus in Combination with Exemestane: A Review of its Use in the Treatment of Patients with Postmenopausal Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer

  2013cited by this paper
• Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2.

  2013cited by this paper
• Oral and intravenously administered mTOR inhibitors for metastatic renal cell carcinoma: pharmacokinetic considerations and clinical implications.

  2013cited by this paper
• Population Pharmacokinetics and Pharmacogenetics of Everolimus in Renal Transplant Patients

  2012cited by this paper
• Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

  2012cited by this paper
• Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.

  2012cited by this paper
• CYP3A5 Genotype Does Not Influence Everolimus In Vitro Metabolism and Clinical Pharmacokinetics in Renal Transplant Recipients

  2011cited by this paper
• Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study.

  2011cited by this paper
• Natural history, management and pharmacokinetics of everolimus-induced-oral ulcers: insights into compliance issues.

  2011cited by this paper
• The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus after heart transplantation

  2011cited by this paper
• Everolimus for advanced pancreatic neuroendocrine tumors.

  2011cited by this paper
• Phase 3 trial of everolimus for metastatic renal cell carcinoma

  2010cited by this paper
• Targeting the mTOR signaling network for cancer therapy.

  2009cited by this paper
• FDG uptake is a surrogate marker for defining the optimal biological dose of the mTOR inhibitor everolimus in vivo

  2009cited by this paper
• Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial.

  2008cited by this paper
• Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors.

  2008cited by this paper
• Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors.

  2008cited by this paper
• Identifying optimal biologic doses of everolimus (RAD001) in patients with cancer based on the modeling of preclinical and clinical pharmacokinetic and pharmacodynamic data.

  2008cited by this paper
• Phase 1 trial of everolimus and gefitinib in patients with advanced nonsmall‐cell lung cancer

  2007cited by this paper
• Current development of mTOR inhibitors as anticancer agents

  2006cited by this paper
• Blood Concentrations of Everolimus Are Markedly Increased by Ketoconazole

  2005cited by this paper
• Effect of Rifampin on Apparent Clearance of Everolimus

  2002cited by this paper

• BiomarkerKB: An Integrated Knowledgebase Supporting Biomarker-Centric Exploration of Biomedical Data

  2026cites this paper
• Genetic insight into lung neuroendocrine tumors: Notch and Wnt signaling pathways as potential targets

  2025cites this paper
• The Role of Precision Dosing and Therapeutic Drug Monitoring in Precision Oncology: A Single-centre Experience with Everolimus

  2025influential citation
• The relationship between dose, concentration and toxicity of everolimus in the treatment of neuroendocrine tumors: A prospective observational study

  2025cites this paper
• A Narrative Review of Chromatographic Bioanalytical Methods for Quantifying Everolimus in Therapeutic Drug Monitoring Applications

  2024influential citation
• Examining the Association between Immunosuppressants and Wound Healing: A Narrative Review

  2024cites this paper
• Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

  2024cites this paper
• The mitochondriogenic but not the immunosuppressant effects of mTOR inhibitors prompt neuroprotection and delay disease evolution in a mouse model of progressive multiple sclerosis.

  2023cites this paper
• Examining the association of immunosuppressants and wound healing: a narrative review

  2023cites this paper
• EVEROLIMUS THERAPEUTIC DRUG MONITORING IN A CANCER RENAL CANCER PATIENT WHEN DOUBLE DRUG-DRUG INTERACTION IS DETECTED AND A REVIEW OF THE LITERATURE

  2023cites this paper
• Mass spectrometry quantitation of immunosuppressive drugs in clinical specimens using online solid-phase extraction and accurate-mass full scan-single ion monitoring

  2023cites this paper
• Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation

  2023cites this paper
• New advances in the research of clinical treatment and novel anticancer agents in tumor angiogenesis.

  2023cites this paper
• First reported double drug–drug interaction in a cancer renal patient under everolimus treatment: therapeutic drug monitoring and review of literature

  2023cites this paper
• In Silico Identification of Therapeutic Targets and Novel Drug Candidates for Malignant Peripheral Nerve Sheath Tumors.

  2023cites this paper
• Exploring the role of PI3K/AKT/mTOR inhibitors in hormone-related cancers: A focus on breast and prostate cancer.

  2023cites this paper
• New approaches for patients with advanced radioiodine-refractory thyroid cancer

  2022cites this paper
• Everolimus pharmacokinetics and exposure-response relationship in Japanese patients with advanced breast cancer

  2022cites this paper
• Therapeutic Drug Monitoring of Protein Kinase Inhibitors in Breast Cancer Patients.

  2021cites this paper
• Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer

  2021cites this paper
• Co-treatment With Everolimus, an mTOR-Specific Antagonist, or Downregulation of ELK1 Enhances the Sensitivity of Pancreatic Cancer Cells to Genistein

  2021cites this paper
• Real-world pharmacokinetics and pharmacodynamics of everolimus in metastatic breast cancer

  2021cites this paper
• The New Direct-Acting Oral Anticoagulants Need to be Monitored!

  2020cites this paper