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.

[PURPOSE] Anti-EGFR mAb therapy improves the clinical outcome of patients with metastatic colorectal cancer (mCRC). This study assessed the predictive value of early [18F]fluorodeoxyglucose ([18F]FDG) PET/CT after one anti-EGFR mAb treatment in patients with mCRC.

[PATIENTS AND 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 before the 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] In patients with RAS/BRAF wild-type left-sided mCRC, the clinical benefit rate was 92% (31% partial response, 61% stable disease), with a median progression-free survival of 5.7 months (95% CI, 5.2-10). Seventy-five patients, including those with right-sided mCRC, were eligible for metabolic response analysis. Patients with clinical benefit (n = 57) showed a mean decrease in sum TLG of 58% (SD = 19%), compared with 1.9% (SD = 36%) in those without clinical benefit (n = 18; P = 0.003). A threshold of <15% reduction in sum TLG had a 100% negative predictive value for clinical benefit. Metabolic responders exhibited longer progression-free survival than nonresponders [6.5 vs. 1.7 months (P < 0.001)].

[CONCLUSIONS] Selecting patients with left-sided RAS/BRAF wild-type mCRC resulted in a 92% clinical benefit rate from anti-EGFR mAb monotherapy. Early [18F]FDG PET/CT identified nonresponders with 100% accuracy, offering promising clinical utility when tumor mutational status is unavailable.