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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-04-2020 | Cetuximab | Original Article

[⁸⁹Zr]Zr-cetuximab PET/CT as biomarker for cetuximab monotherapy in patients with RAS wild-type advanced colorectal cancer

Authors: E. J. van Helden, S. G. Elias, S. L. Gerritse, S. C. van Es, E. Boon, M. C. Huisman, N. C. T. van Grieken, H. Dekker, G. A. M. S. van Dongen, D. J. Vugts, R. Boellaard, C. M. L. van Herpen, E. G. E. de Vries, W. J. G. Oyen, A. H. Brouwers, H. M. W. Verheul, O. S. Hoekstra, C. W. Menke-van der Houven van Oordt

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2020

Abstract

Purpose

One-third of patients with RAS wild-type mCRC do not benefit from anti-EGFR monoclonal antibodies. This might be a result of variable pharmacokinetics and insufficient tumor targeting. We evaluated cetuximab tumor accumulation on [⁸⁹Zr]Zr-cetuximab PET/CT as a potential predictive biomarker and determinant for an escalating dosing strategy.

Patients and methods

PET/CT imaging of [⁸⁹Zr]Zr-cetuximab (37 MBq/10 mg) after a therapeutic pre-dose (500 mg/m² ≤ 2 h) cetuximab was performed at the start of treatment. Patients without visual tumor uptake underwent dose escalation and a subsequent [⁸⁹Zr]Zr-cetuximab PET/CT. Treatment benefit was defined as stable disease or response on CT scan evaluation after 8 weeks.

Results

Visual tumor uptake on [⁸⁹Zr]Zr-cetuximab PET/CT was observed in 66% of 35 patients. There was no relationship between PET positivity and treatment benefit (52% versus 80% for PET-negative, P = 0.16), progression-free survival (3.6 versus 5.7 months, P = 0.15), or overall survival (7.1 versus 9.4 months, P = 0.29). However, in 67% of PET-negative patients, cetuximab dose escalation (750–1250 mg/m²) was applied, potentially influencing outcome in this group. None of the second [⁸⁹Zr]Zr-cetuximab PET/CT was positive. Eighty percent of patients without visual tumor uptake had treatment benefit, making [⁸⁹Zr]Zr-cetuximab PET/CT unsuitable as a predictive biomarker. Tumor SUV_peak did not correlate to changes in tumor size on CT (P = 0.23), treatment benefit, nor progression-free survival. Cetuximab pharmacokinetics were not related to treatment benefit. BRAF mutations, right-sidedness, and low sEGFR were correlated with intrinsic resistance to cetuximab.

Conclusion

Tumor uptake on [⁸⁹Zr]Zr-cetuximab PET/CT failed to predict treatment benefit in patients with RAS wild-type mCRC receiving cetuximab monotherapy. BRAF mutations, right-sidedness, and low sEGFR correlated with intrinsic resistance to cetuximab.

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Title: [89Zr]Zr-cetuximab PET/CT as biomarker for cetuximab monotherapy in patients with RAS wild-type advanced colorectal cancer
Authors: E. J. van Helden
S. G. Elias
S. L. Gerritse
S. C. van Es
E. Boon
M. C. Huisman
N. C. T. van Grieken
H. Dekker
G. A. M. S. van Dongen
D. J. Vugts
R. Boellaard
C. M. L. van Herpen
E. G. E. de Vries
W. J. G. Oyen
A. H. Brouwers
H. M. W. Verheul
O. S. Hoekstra
C. W. Menke-van der Houven van Oordt
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Keywords: Cetuximab
Biomarkers
Colorectal Cancer
Colorectal Cancer
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04555-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

[⁸⁹Zr]Zr-cetuximab PET/CT as biomarker for cetuximab monotherapy in patients with RAS wild-type advanced colorectal cancer

Abstract

Purpose

Patients and methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Patients and methods

Results

Conclusion

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