Analysis of PTEN in patients with advanced colorectal cancer (CRC) receiving capecitabine alone or in combination with bevacizumab with or without mitomycin C in the phase III AGITG MAX trial.

Abstract

3534 Background: There is an urgent need for potential biomarkers for anti-VEGF therapies. The tumour suppressor gene PTEN is thought to have a potential role as a biomarker for anti-EGFR therapy in CRC, but there is also evidence that decreased levels of PTEN leads to increased expression of VEGF suggesting a potential relationship to outcome with anti-VEGF therapy*. The prognostic value of PTEN also remains controversial. Methods: Patients enrolled in the Phase III MAX trial of capecitabine (C) +/- bevacizumab (B) (+/- mitomycin C (M)) with available tissue were analysed for PTEN expression (loss v no loss) as assessed using a Taqman copy number assay to measure copy number variation at the PTEN locus. PTEN status was correlated with progression-free survival (PFS) and overall survival (OS) outcomes. The predictive value of PTEN status for bevacizumab efficacy was also examined. Results: Of the original 471 patients enrolled in the trial, tissue from 302 (64.1%) patients were analysed. Baseline characteristics of those with and without tissue were comparable. PTEN loss was observed in 38.7% of patients. There was no relationship between PTEN loss and KRAS or BRAF mutation. Patients with PTEN loss were more likely to have rectal primary (p=0.01) and less likely to have lung metastasis (p=0.03). By using the comparison of C v CB+CBM, PTEN status was not significantly predictive of the effectiveness of B for PFS or OS (Table). PTEN status is also not prognostic for PFS or OS in multivariate analyses adjusting for other baseline factors (Table). Conclusions: PTEN status did not significantly predict different benefit with anti-VEGF therapy. PTEN status was also not prognostic for survival in advanced colorectal cancer. [Table: see text]