We previously reported the results of a randomized phase II controlled trial comparing mFOLFOX6 plus bevacizumab (Bmab) with mFOLFOX6 plus cetuximab (Cmab) for KRAS wild-type (wt) colorectal cancer (CRC) with liver-limited metastases that were not optimally resectable. The current study is the first to examine the role of histopathologic response based on the study data of anti-VEGF versus anti-EGFR antibody.
In the ATOM trial, KRAS wild-type CRC patients with liver-limited metastases were eligible if the number of lesions was more than 5 and/or the size of lesions was more than 5cm in the maximum diameter. The primary endpoint was progression-free survival (PFS). Of 116 eligible patients, patients who underwent liver metastasectomy were evaluated for histopathologic response in this study. Resected liver specimens were assessed by the independent pathological review committee. Preplanned pathological assessments included tumor regression grade (TRG), dangerous halo, and sinusoidal obstruction of resected liver specimens. Patients were categorized into major histopathologic response (MjHR) if they had TRG of 1 (viable tumor cells = 0%) or 2 (< 25%), partial histopathologic response (PHR) if they had TRG of 3 (< 50%), or no histopathologic response (NHR) if they had TRG of 4 (< 75%) or 5 (> 75%).
A total of 59 patients had TRG evaluation based on resected specimens by liver metastasectomy. Of those, 55 (28 in Bmab arm, 27 in Cmab arm) were eligible for analysis. In the Bmab arm, the number of patients with MjHR/PHR/NHR was 12/1/15 (43/4/54%); in the Cmab arm, 13/10/4 (48/37/15%). Median PFS of patients with a MjHR or PHR/NHR was 8.3 or 4.4 months in the Bmab arm and Not Reached or 5.4 months in the Cmab arm. Patients with a MjHR had a longer PFS than those with a PHR/NHR in both the Bmab arm (hazard ratio [HR], 0.50 (95%CI, 0.19-1.28)) and the Cmab arm (HR, 0.17 (95%CI, 0.05-0.58)).
In the TRG assessment, the proportion of MjHR was similar between the two arms. The impact of MjHR on PFS as compared to PHR/NHR was observed in both arms. Further results regarding other assessments will be presented.
Clinical trial identification
Legal entity responsible for the study
ATOM study group.
All authors have declared no conflicts of interest.