Change in metabolic tumor activity on 18F-FDG PET after a single dose of cetuximab to predict for treatment benefit, PFS, and OS in patients with advanced colorectal cancer.

Abstract

11519 Background: Despite RAS selection, one third of patients with metastatic RAS wild-type colorectal cancer (mCRC) do not benefit from anti-EGFR inhibitors. Therefore, an additional or more accurate predictive biomarker is needed to identify patients with primary resistant mCRC. Methods: In the IMPACT-CRC trial (NCT02117466) patients with chemotherapy refractory mCRC received 500 mg/m2 cetuximab every 2 weeks. Before the first dose and just before the second dose, patients underwent a 18F-FDG PET/CT (FDG PET). PET scans were quantitatively assessed by manual tumor delineation of ≤ 5 lesions, 2 per organ. Outcome is reported in total lesion glycolysis (TLG), defined as metabolic tumor volume times mean standard uptake value of the tumor. An optimal threshold to assess metabolic response was defined as decrease in TLG ≥15%. Quantitative data were correlated with CT evaluation after 8 weeks of treatment according to RECIST v1.1. Results: Out of 35 patients, 1 was excluded due to an infusion reaction. Median age was 64 years, 74% was male, 4 patients had a BRAF mutated tumor and 9 patients had right-sided primary tumors. 62% of patients had stable disease or partial response on CT after 8 weeks. At the time of this analysis, 88% of patients had progressive disease and 71% had died. Of the patients with right-sided tumors 11% had treatment benefit, compared to 80% in the left-sided group (p = 0.001). None of the 9 metabolic non-responders had treatment benefit, whereas 83% of the metabolic responders had treatment benefit according to RECIST v1.1. After adjustment for age, WHO score, BRAF mutation, sex and primary tumor site, FDG PET response remained correlated with PFS and OS (p = 0.002 and p = 0.014). Conclusions: Early evaluation of metabolic response after 1 dose of cetuximab is highly and independently predictive for treatment benefit with a 100% negative predictive value. Implementation of early FDG-PET evaluation in daily clinical practice can prevent unnecessary toxicity, costs of ineffective treatment and allows timely treatment adjustment for patients with mCRC undergoing anti-EGFR treatment. Clinical trial information: NCT02117466.