Early prediction of anti-epidermal growth factor receptor (EGFR) therapy with 18[F]FDG-PET: A preclinical and clinical correlation

Abstract

14064 Background: Predictive biomarkers for response to anti-EGFR therapy are of significant clinical importance. We hypothesized that early changes in 18[F]FDG tumor uptake predict response to anti-EGFR therapy. We investigated this in a mice model and correlated these findings with human patients undergoing anti-EGFR therapy. Methods: Mice bearing two head and neck squamous cell cancer (HnNSCC) xenografts (Hep2, Cal27) received vehicle or erlotinib for 3 weeks. 18[F]FDG uptake were imaged with small animal micro- PET at baseline and after 1 week of therapy, and reported in SUVmax. For clinical correlation, human patients with HnNSCC receiving erlotinib were identified from an ongoing clinical trial. 18[F]FDG-PET images were obtained at baseline and after 2 weeks of erlotinib monotherapy. Tumor specimens were obtained by fine-needle aspiration biopsy at the same time as PET. A panel of pharmacodynamic markers (including Ki-67 and pMAPK) were assessed . Results: Hep2 was resistant to erlotinib therapy (Tumor/Control [T/C]: 0.8) while Cal27 was sensitive (T/C: 0.2). SUVmax in the resistant Hep2 xenografts was not significantly different from the control (86% ± 70% of control) while SUVmax in the treated sensitive Cal27 xenografts showed a significant decrease than control (-2% ± 7%). Ki-67 in the treated Hep2 was not significantly different from control while that in Cal27 was <50% of control. For clinical correlation, ki-67 score was higher after 2 weeks in the patient resistant to erlotinib monotherapy by 18[F]FDG-PET (SUVmax increased by 14%, ± 11%) and was lower in the patient who was 18[F]FDG-PET sensitive (SUVmax decreased by 56%, ± 13%). pMAPK decreased in all cases and had a poor correlation with efficacy. Conclusions: Early dynamic changes in 18[F]FDG tumor uptake is predictive of response to anti-EGFR therapy and correlates with changes in ki-67 expression, both in a preclinical and a clinical scenario. No significant financial relationships to disclose.