Use of the intensity of membranous EGFR staining by immunohistochemistry to predict the efficacy of chemotherapy containing cetuximab in KRAS wild-type patients with metastatic colorectal cancer: A retrospective analysis.

Abstract

516 Background: KRAS mutation status is a strong predictive factor for anti-EGFR monoclonal antibody therapy efficacy in metastatic colorectal cancer (mCRC). In the BOND trial, objective response rates to cetuximab in irinotecan-refractory mCRC were not significantly different based on the intensity of EGFR staining by immunohistrochemistry (IHC). However, this result was not evaluated by KRAS mutation status, so we retrospectively evaluated the relationship between the efficacy of chemotherapy containing cetuximab and the intensity of membranous EGFR staining in KRAS wild type (KRAS-WT) patients. Methods: Between August 2008 and July 2011, specimens of 391 CRC patients were collected by endoscopic biopsy or surgical resection. EGFR staining by IHC and genetic screening for KRAS status were performed and intensity of EGFR staining was scored by the Guidelines for Interpreting EGFR pharmDx, DAKO. We analyzed 94 KRAS-WT patients who received combination chemotherapy with an irinotecan-regimen plus cetuximab or cetuximab monotherapy and met the following criteria: histologically proven mCRC adenocarcinoma , at least 1 previous regimen of standard fluoropyrimidine - containing chemotherapy , ECOG PS score 0-2, and adequate hepatic and renal function. Patients were classified into 2 groups by intensity of EGFR staining: (A) absence of staining and weakly to moderately positive (IHC 1+ and IHC 2+), (B) strongly positive (IHC 3+). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and compared in Groups A and B by the log-rank test. Results: There was no significant difference in patient characteristics between the 2 groups except for primary site. The median PFS of Groups A (n=76) and B (n=18) were 5.4 months and 9.1 months (p= 0.029), the median OS was 8.1 months and 13.2 months (p=0.054) and response rate was 20.1% and 33.3%, respectively. Conclusions: In KRAS-WT patients with fluoropyrimidine-containing chemotherapy-refractory mCRC, strong intensity of EGFR staining by IHC might be predictive for efficacy of chemotherapy containing cetuximab.