Wt Kras and gene expression levels of VEGFR2, EGFR, and ERCC-1 associated with progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC) treated with first-line 5-FU or capecitabine with oxaliplatin and bevacizumab (FOLFOX/BV or XELOX/BV)

Abstract

4056 Background: While wild type (wt) Kras is associated with improved outcome to anti-EGFR therapy in pts with mCRC, there are no identified predictors of outcome for FOLFOX/BV. We evaluated Kras status and expression of genes involved in angiogenesis, DNA repair and 5-FU metabolism in 68 patients treated with FOLFOX/BV or XELOX/BV. These genes included VEGF, VEGF-receptor 2 (KDR), Cox-2, IL 6 and 8, chemokine-receptors 1 & 2, EGFR and ERCC-1. Methods: Tissue samples from 68 patients with mCRC were analyzed. mRNA was extracted from laser-capture-microdissected tumor tissue. cDNA was prepared by reverse transcription and quantitation of the candidate genes was performed using a fluorescence- based real-time detection method (TaqMan). Allele specific RT-PCR was performed to determine Kras mutation status in codons 12 and 13. Results: There were 68 pts (38 males, 30 females), median age: 56 years (range 29–81). All received first line 5FU, oxaliplatin and BV (28 FOLFOX/BV, 40 XELOX/BV). Radiologic response: 1 CR, 39/68 (57%) PR, 27/68 (40%) SD, and 1 PD. Median OS is not reached. At a median follow-up of 32.0 months (mo) (range: 2.3–47.8 mo), the median PFS was 12.4 mo (95% CI: 9.8–15.2). Kras mutation was identified in 39 pts (57%). RR was 64% in pts with wt Kras and 52% in pts with mutant Kras (p=0.33). PFS was significantly longer for pts with wt kras compared to pts with mutant kras (13.7 mo [95% CI: 6.9–13.2] versus 8.3 mo [95%CI: 6.9–13.2], P=0.039). High EGFR (median PFS: 15.2 mo; 95% CI 11.7–16.5 mo), high VEGFR2 (median PFS: 13.9 mo; 95% CI 11.0–16.5 mo), and low ERCC1 (median PFS: 12.4 mo; 95% CI 10.9–16.4 mo) were associated with longer PFS compared to low EGFR (median PFS: 7.9 mo; 95% CI 6.9–11.0 mo, P=0.040), low VEGFR2 (median PFS: 7.2 mo; 95% CI 6.5–8.1 mo, P=0.032), and high ERCC1 (median PFS: 9.6 mo; 95% CI 5.8–15.2 mo, P=0.045). Conclusions: To our knowledge, this is the first report of a potential association between Kras status as well as gene expression levels of VEGFR2, ERCC-1 and EGFR and clinical outcome to FOLFOX/BV therapy in pts with mCRC. Prospective clinical trials are needed to validate these results. [Table: see text]