• Adjuvant/Neoadjuvant Therapy
• Gastrointestinal Cancers
• Oncology Clinical Trials

• Oncology

Codon 12 KRAS mutations are an independent predictor of time to recurrence (TTR) and disease-free survival (DFS) in patients with Stage III colon cancer who received adjuvant treatment. Julien Taieb, Assistance Publique Hôpitaux de Paris, Paris, France, presented data from a post hoc analysis of the Combination Chemotherapy With or Without Cetuximab in Treating Patients With Stage III Colon Cancer That Was Completely Removed by Surgery trial [PETACC8; Taieb J et al. Ann Oncol 2014 (abstr O-0024)].

KRAS mutations may be prognostic in colon adenocarcinoma, but the evidence is inconclusive. The purpose of this post hoc analysis was to determine if KRAS mutations are prognostic in patients with Stage III colon adenocarcinoma who received adjuvant leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX4) with or without cetuximab.

The international, open-label, Phase 3 PETACC8 trial randomly assigned patients with resected Stage III colon cancer to receive FOLFOX4 with or without cetuximab for a median follow-up time of 3.3 years [Taieb J et al. Lancet Oncol 2014]. A protocol amendment restricted further enrollment to patients with wild-type KRAS mutations, and the intention-to-treat population included patients with wild-type KRAS. The primary end point of DFS was similar among both arms in the intention-to-treat population and in patients with KRAS mutations in exon 2 (including codons 12 and 13). Adverse events such as acne-like rash, diarrhea, mucositis, and infusion reactions occurred more frequently in the cetuximab arm.

In this analysis, 638 out of 1657 tumors harbored KRAS mutations [Taieb J et al. Ann Oncol 2014 (abstr O-0024)]. TTR was significantly associated with KRAS mutations located at codon 12 (HR, 1.67; 95% CI, 1.35 to 2.04; p < .001) compared with patients who had tumors with wild-type KRAS or BRAF. Similarly, DFS was associated with KRAS mutations at codon 12. Mutations at codon 13 were not significantly associated with TTR or DFS. In addition, distal tumors were more likely to relapse in patients with KRAS mutations in codon 12 (HR, 1.96; 95% CI, 1.51 to 2.56; p < .0001).

In conclusion, Prof. Taieb indicated that, in his opinion, the data from this post hoc analysis of the PETACC8 trial suggest that codon 12 KRAS mutations predicted TTR and DFS in patients with Stage III distal colon cancer. He called for future studies to evaluate KRAS mutations as well as tumor location.

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