574P - Clinical outcome of cetuximab for metastatic colorectal cancer patients harboring KRAS codon61, KRAS codon146, BRAF, NRAS or PIK3CA mutations

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Presenter Eiji Shinozaki
Authors E. Shinozaki1, H. Bando2, T. Nishina3, K. Yamazaki4, S. Kadowaki5, S. Yuki6, S. Kajiura7, K. Tsuchihara8, S. Fujii9, T. Yoshino10
  • 1Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 2Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa, Chiba/JP
  • 3Dept. Of Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama/JP
  • 4Gastrointestinal Oncology And Endoscop, Shizuoka Cancer Center, JP-411-8777 - Shizuoka/JP
  • 5Division Of Gastroenterology, Saitama Cancer Center, Saitama/JP
  • 6Gastroenterology, Hokkaido University Hospital, Sapporo/JP
  • 7The Third Departoment Of Internal Medicine, University of Toyama, Toyama/JP
  • 8Cancer Physiology Project, Research Center For Innovative Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 9Pathology Division, Research Center For Innovative Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 10Department Of Endoscopy & Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa, Chiba/JP

Abstract

Background

Retrospective pooled analyses have identified KRAS, BRAF, NRAS, and PIK3CA mutations as potentially negative predictive factors for colorectal cancer patients treated with Cetuximab (Cmab). We developed a novel kit that applies Luminex technology for detection of mutations in KRAS codon61, KRAS codon146, BRAF, NRAS, and PIK3CA in a single reaction (GENOSEARCH Mu-PACK).

Methods

Formalin-fixed paraffin-embedded tumor samples and clinical data of colorectal cancer patients treated with Cmab-containing regimens were collected from 7 Japanese centers. KRAS, BRAF, NRAS and PIK3CA gene statuses were determined, both by our kit and by direct-sequencing (DS). Objective response, progression-free survival (PFS), and overall survival (OS) were evaluated in subgroups determined by mutation status.

Results

A total of 83 samples were collected. The concordance rate between our kit and DS data was 100%. Our kit results identified 3 samples with mutations in KRAS codon 61 (3.6%), 2 in KRAS codon 146 (2.4%), 4 in BRAF (4.8%), 2 in NRAS (2.4%), and 4 in PIK3CA (4.8%). We also identified 21 samples with mutations in KRAS codon 12, 13 (25.3%) by using Luminex technology. All of these mutations, except for PIK3CA, were mutually exclusive. The response rate for all patients in the study was 24.4%, whereas the response rate for the group of patients with all wild-type tumors was 40.8%. The median PFS values of patients with all wild-type tumors (N = 49), with KRAS codon12, 13 mutation (N = 21), and with any of KRAS codon61, KRAS codon146, BRAF, NRAS, or PIK3CA mutations (N = 12) were, respectively, 6.4 months (95%CI: 2.9, 10.0), 2.7 months (95%CI: 1.2, 4.2), and 1.6 months (95%CI: 1.5, 1.7) (Log Rank test, P < 0.0001). The median OS values were, respectively, 15.6 months (95%CI: 10.1, 20.2), 8.2 months (95%CI: 5.7, 10.7), and 6.3 months (95%CI: 1.9, 10.7) (Log Rank test, P < 0.0001).

Conclusions

Patients with KRAS codon61, KRAS codon146, BRAF, NRAS, and PIK3CA mutations may not derive clinical benefits from Cmab, nor would patients with KRAS codon 12, 13 mutations. This newly developed detection kit is robust and practical for examining a patient's KRAS codon61, codon146, BRAF, NRAS, and PIK3CA gene status.

Disclosure

All authors have declared no conflicts of interest.