[Zr-89]Zr-cetuximab PET/CT as biomarker for cetuximab monotherapy in patients with RAS wild-type advanced colorectal cancer
van Helden, E J; Elias, S G; Gerritse, S L; van Es, S C; Boon, E; Huisman, M C; van Grieken, N C T; Dekker, H; van Dongen, G A M S; Vugts, D J; Boellaard, R; van Herpen, C M L; de Vries, E G E; Oyen, W J G; Brouwers, A H; Verheul, H M W; Hoekstra, O S; Menke-van der Houven van Oordt, C W
(2020) European Journal of Nuclear Medicine and Molecular Imaging, volume 47, issue 4, pp. 849 - 859
(Article)
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:
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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 SUVpeak 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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Keywords: CT, Cetuximab, Colorectal cancer, Imaging biomarker, PET, Targeted therapy, PET/CT, Radiology Nuclear Medicine and imaging
ISSN: 1619-7070
Publisher: Springer Verlag
Note: Funding Information: This study was funded by Alpe d’HuZes, Dutch Cancer Society (KWF 2012-5565). Funding Information: Evaluation of study (imaging) data was supported by online data analysis software from an IT research infrastructure project, CTMM-TraIT, to allow multicenter blinded PET reviewing []. Publisher Copyright: © 2019, The Author(s).
(Peer reviewed)