Early [18F]FDG PET/CT response after a single dose of anti-EGFR therapy as a predictive biomarker for treatment benefit in patients with advanced colorectal cancer.

Abstract Purpose: Anti-Epidermal Growth Factor Receptor monoclonal antibody (anti-EGFR mAb) therapy improve the clinical outcome of patients with metastatic colorectal cancer (mCRC).. This study assessed the predictive value of early [18F]fluorodeoxyglucose-positron emission tomography/Computed tomography ([18F]FDG PET/CT) after one anti-EGFR mAb treatment in patients with mCRC. Patients & Methods: The multicenter IMPACT-CRC study (NCT02117466) prospectively included patients with mCRC receiving second- or third line anti-EGFR mAb monotherapy. Clinical benefit (complete/partial response or stable disease per RECIST version 1.1) was determined with CT at 8 weeks. [18F]FDG PET/CT scans were performed at baseline and pre-second treatment cycle (2 weeks). Total Lesion Glycolysis (TLG) change was evaluated as a predictive biomarker for clinical benefit using a predetermined data-driven threshold. Results: Inpatients with RAS/BRAF wt left-sided mCRC, the clinical benefit rate was 92% (31% partial response, 61% stable disease), with median PFS of 5.7 months (95% CI 5.2-10). Seventy-five patients including right-sided mCRC were eligible for metabolic response analysis. Patients with clinical benefit (n=57) showed a mean decrease in sumTLG of 58% (SD 19%), compared to 1.9% (SD 36%); in those without clinical benefit (n=18) (P =0·003). A threshold of <15% reduction in sumTLG had a 100% negative predictive value for clinical benefit. Metabolic responders exhibited longer progression-free survival (PFS) than non-responders (6.5 versus 1·7 months (P<0·001)). Conclusions: Selecting patients with left-sided RAS/BRAF wt mCRC resulted in a 92% clinical benefit rate from anti-EGFR mAb monotherapy. Early [ 18F]FDG PET/CT identified non-responders with 100% accuracy, offering promising clinical utility when tumor mutational status is unavailable.