532P - PTEN and advanced colorectal cancer (CRC): analysis from the phase III AGITG max trial of capecitabine alone or in combination with bevacizumab +/-...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter Timothy Price
Authors T.J. Price1, J. Hardingham2, C. Lee3, A. Townsend4, J. Wrin2, K. Wilson3, A. Weickhardt5, R.J. Simes3, C. Munroe5, N. Tebbutt6
  • 1The Queen Elizabeth Hospital, 5012 - Woodville South/AU
  • 2Department Of Medical Oncology, The Queen Elizabeth Hospital, 5012 - Woodville South/AU
  • 3Ctc, University of Sydney, Sydney/AU
  • 4Medical Oncology, The Queen Elizabeth Hospital, 5012 - Woodville South/AU
  • 5Oncology, Ludwig Institute, Melbourne/AU
  • 6Medical Oncology, Austin Hospital, AU-3084 - Heidelberg/AU

Abstract

Background

The tumour suppressor gene PTEN may have a role as a biomarker for anti-EGFR therapy in CRC. As PTEN expression also has a relationship with VEGF expression via HIF-1 alpha, and the PI3K/mTOR pathways, we have explored the potential that PTEN loss may be predictive of outcome with an anti-VEGF agent. We also assess the prognostic value of PTEN as this remains controversial.

Methods

Patients enrolled in the Phase III MAX trial of capecitabine (C) +/- bevacizumab (B) (+/- mitomycin C (M)) with available tissues 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. The predictive value of PTEN status for bevacizumab efficacy was examined. PTEN status was also correlated with progression-free survival (PFS) and overall survival (OS) outcomes, and a second sub analysis grouping PTEN by KRAS/BRAF status was also performed.

Results

Of the original 471 patients enrolled in the trial, tissues from 302 (64.1%) patients were analysed. Baseline characteristics of those with and without tissues were comparable. PTEN loss was observed in 38.7% of patients. There was no relationship between PTEN loss and KRAS or BRAF mutation (KRAS/BRAF MT v WT with PTEN loss; 34%/37% v 41%/39% respectively). PTEN loss was associated with rectal primary (p = 0.01) and lower rates of 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 (Loss v No Loss PFS HR 0.9 (0.7-1.16), OS HR 1.04 (0.79-1.38)). PTEN was also not prognostic when assessed by KRAS and BRAF status.

Conclusions

PTEN status did not significantly predict different benefit with anti-VEGF therapy. PTEN status was not prognostic for survival in advanced colorectal cancer.

C vs CB + CBM Loss No loss P value (for interaction)
PFS HR 0.51 0.33 - 0.79 HR 0.72 0.52-0.98 P = .26
OS HR 0.75 0.47-1.19 HR 1.00 0.70-1.43 P = .35
Disclosure

T. Price: Uncompensated Advisory board Merck, AMGEN and Roche.Travel grants Merck and AMGEN.

N. Tebbutt: Uncompensated Ad board Roche.

All other authors have declared no conflicts of interest.