533P - Somatic K-RAS mutation is predictive in colorectal cancer, but is it prognostic? A systematic review and meta-analysis

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter Iain Tan
Authors I.B. Tan1, T. Seah2, S.L. Koo2, S. Choo2, C.K. Tham2, D. Chong3
  • 1Dept. Medical Oncology, National Cancer Centre, 169610 - Singapore/SG
  • 2Medical Oncology, National Cancer Centre, 169610 - Singapore/SG
  • 3National Cancer Centre, 169610 - Singapore/SG

Abstract

Background

Consistent data from retrospective molecular analysis performed in multiple phase 3 Randomized controlled trials (RCTs) have established that somatic KRAS mutation (K-RAS-mt) is a strong predictor of non-response to anti-epidermal growth factor receptor antibody (anti-EGFR) therapy in colorectal cancer. However, K-RAS's role as a prognostic marker remains undefined. We performed a systematic review and meta-analysis to determine the prognostic significance of somatic K-RAS mutation.

Methods

We searched MEDLINE, EMBASE, and CENTRAL databases, ESMO and ASCO meeting proceedings for Phase 3 RCTs in colorectal cancer for which retrospective molecular analysis of K-RAS mutation was performed on archival patient samples. Studies were pooled according to setting of treatment (adjuvant, 1st line metastatic, refractory). Meta-analysis was performed using random-effects model. The outcomes of interest were disease-free survival in the adjuvant setting and overall survival (OS) for advanced disease.

Results

14 Phase 3 trials which enrolled 18,991 patients were identified, of whom 13,143 had K-RAS status ascertained (69.2% range: 48%-100%) In pooled data of patients who did not receive anti-EGFR therapy and had K-RAS status ascertained, patients with K-RAS-wt patients had better survival outcomes compared to K-RAS-mt patients. In the adjuvant setting (Disease Free Survival HR 0.75 95% CI: 0.66-0.87, p < 0.001), 1st line metastatic (Overall Survival: HR 0.85 (95% CI: 0.76-0.96), p < 0.01) and refractory disease (Overall Survival: HR 0.75 95% CI: 0.64-0.89, p < 0.01).

Conclusion

Beyond being a predictive marker of non-response to EGFR antibodies, among patients with early stage, 1st line metastatic and refractory colorectal cancer who do not receive anti-EGFR therapy, K-RAS is a negative prognostic marker.

Disclosure

All authors have declared no conflicts of interest.