Histological response, pattern of tumor destruction and clinical outcome after neoadjuvant chemotherapy including bevacizumab or cetuximab in patients undergoing liver resection for colorectal liver metastases

Abstract

Aim: We investigated whether the type of antibody [bevacizumab (bev) or cetuximab (cet)] added to neoadjuvant combination chemotherapy before curative liver resection was associated with histological response, the pattern of tumor destruction and clinical outcome in patients with colorectal liver metastases (CLM).

Methods: We investigated 138 patients with KRAS wild-type status (codon 12, 13 and 61) who received neoadjuvant chemotherapy including bev (n = 101) or cet (n = 37). The primary endpoint was histological response. Secondary endpoints were necrosis and fibrosis of metastases, radiological response, recurrence-free survival (RFS) and overall survival (OS).

Results: Histological response was not significantly different between the two groups (P = 0.19). A significantly higher fraction of patients in the bev group showed necrosis of the metastases of ≥ 50% (P < 0.001), while a higher fraction of patients in the cet group showed fibrosis of ≥ 40% (P = 0.030). Radiological response was not significantly different (P = 0.17). Median RFS was significantly shorter in the cet group in univariable analysis (HR 1.59 (95% CI 1.00, 2.51), P = 0.049), but this difference did not remain significant in multivariable analysis (P = 0.45). The 3-year OS rate was not significantly different (P = 0.73).

Conclusions: The addition of bevacizumab to combination chemotherapy showed more necrosis but less fibrosis of metastases compared to cetuximab and a trend towards higher histological and radiological response and longer RFS. Further investigations of biological tumor characteristics are required to individualize treatment combinations.

Keywords: Bevacizumab; Cetuximab; Colorectal liver metastases; Histological response; Pattern of tumor destruction; Survival.