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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
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.
- 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 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.
- Subjects
COLORECTAL cancer; MONOCLONAL antibodies; PROGRESSION-free survival; CETUXIMAB
- Publication
European Journal of Nuclear Medicine & Molecular Imaging, 2020, Vol 47, Issue 4, p849
- ISSN
1619-7070
- Publication type
Article
- DOI
10.1007/s00259-019-04555-6