KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

Journal Article · Tue Jan 01 04:00:00 EST 2013 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2012.03.048· OSTI ID:22149734

Kim, Sun Young; Shim, Eun Kyung ^[1]; Yeo, Hyun Yang ^[2]; Baek, Ji Yeon ^[1]; Hong, Yong Sang ^[3]; Kim, Dae Yong ^[1]; Kim, Tae Won ^[3]; Kim, Jee Hyun ^[4]; Im, Seock-Ah ^[5]; Jung, Kyung Hae ^[3]

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1. Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)
2. Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)
3. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
4. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of)
5. Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)

Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab.

• OSTI ID: 22149734
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 1 Vol. 85; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CHEMOTHERAPY
GROWTH FACTORS
METASTASES
MUTATIONS
NEOPLASMS
PATIENTS
RADIATION DOSES
RADIOTHERAPY
RECEPTORS
RECTUM