The NEOLETEXE trial: a neoadjuvant cross-over study exploring the lack of cross resistance between aromatase inhibitors

Nazli Bahrami; Torill Sauer; Siri Engebretsen; Belal Aljabri; Vahid Bemanian; Jonas Lindstrøm; Torben Lüders; Vessela Kristensen; Annika Lorentzen; Marie Loeng; Hilde Presterud Ødegård; Jan Øyvind Kvaløy; Ingeborg Berge Vestøl; Stephanie Beate Geisler; Berit Gravdehaug; Joanna Majak Gundersen; Jürgen Geisler

doi:10.2217/fon-2019-0258

The NEOLETEXE trial: a neoadjuvant cross-over study exploring the lack of cross resistance between aromatase inhibitors

Future Oncol. 2019 Nov;15(32):3675-3682. doi: 10.2217/fon-2019-0258. Epub 2019 Sep 12.

Authors

Nazli Bahrami^{1

2

3}, Torill Sauer^{4

3

5}, Siri Engebretsen^{2

3}, Belal Aljabri^{1

3}, Vahid Bemanian^{6

3}, Jonas Lindstrøm^{7

5}, Torben Lüders^{8

5}, Vessela Kristensen^{8

5}, Annika Lorentzen³, Marie Loeng³, Hilde Presterud Ødegård^{1

3}, Jan Øyvind Kvaløy^{1

3}, Ingeborg Berge Vestøl^{1

3}, Stephanie Beate Geisler^{1

3}, Berit Gravdehaug^{2

3}, Joanna Majak Gundersen^{2

3}, Jürgen Geisler^{1

3

5}

Affiliations

¹ Department of Oncology, Akershus University Hospital (AHUS), Lørenskog, Norway.
² Department of Breast & Endocrine Surgery (AHUS), Akershus University Hospital, Lørenskog, Norway.
³ Translational Cancer Research Group, Akershus University Hospital, Lørenskog, Norway.
⁴ Department of Pathology (AHUS), Akershus University Hospital, Lørenskog, Norway.
⁵ Institute of Clinical Medicine, Campus AHUS, University of Oslo, Norway.
⁶ Department of Gene Technology (AHUS), Akershus University Hospital, Lørenskog, Norway.
⁷ Health Services Research Center (AHUS), Akershus University Hospital, Lørenskog, Norway.
⁸ Department of Clinical Molecular Biology (AHUS/EpiGen), Akershus University Hospital, Lørenskog, Norway.

PMID: 31513453
DOI: 10.2217/fon-2019-0258

Abstract

The aromatase inhibitor letrozole (Femar^®/Femara^®) and the aromatase inactivator exemestane (Aromasin^®) differ in their biochemical effect on the aromatase enzyme. Letrozole is a competitive aromatase inhibitor while exemestane binds irreversibly to the aromatase enzyme. This pharmacological difference is of clinical interest since a lack of cross-resistance has been documented. It has been demonstrated in several clinical trials that exemestane may cause a disease regression following resistance to nonsteroidal aromatase inhibitors. The exact mechanism(s) behind this phenomenon is yet unknown. Here, we present the NEOLETEXE trial with the aim of exploring the individual mechanisms involved behind the observed lack of cross resistance. Clinical trial registration: The trial has been approved by the Regional Ethics Committee of South-East Norway (project number 2015/84).

Keywords: aromatase inhibitor; breast cancer; exemestane; letrozole; neoadjuvant.

Publication types

Clinical Trial
Randomized Controlled Trial

MeSH terms

Androstadienes / administration & dosage
Androstadienes / pharmacology
Androstadienes / therapeutic use
Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Antineoplastic Combined Chemotherapy Protocols* / pharmacology
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Aromatase Inhibitors* / pharmacology
Aromatase Inhibitors* / therapeutic use
Breast Neoplasms / drug therapy*
Breast Neoplasms / pathology
Breast Neoplasms / surgery
Cross-Over Studies
Drug Administration Schedule
Drug Resistance, Neoplasm / drug effects*
Estradiol / blood
Female
Humans
Letrozole / administration & dosage
Letrozole / pharmacology
Letrozole / therapeutic use
Neoadjuvant Therapy
Postmenopause
Receptor, ErbB-2 / metabolism
Receptors, Estrogen / metabolism

Substances

Androstadienes
Antineoplastic Agents
Aromatase Inhibitors
Receptors, Estrogen
Estradiol
Letrozole
ERBB2 protein, human
Receptor, ErbB-2
exemestane