709P - The HENT1 immunohistochemistry diagnostic test is predictive of gemcitabine outcome in pancreatic ductal adenocarcinoma

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Hepatobiliary Cancers
Translational Research
Presenter Mitch Raponi
Authors M. Raponi1, J. Isaacson2, H. Hahn3, M. Bartosiewicz2, A. Magnusson3, K. Lin2, L. Rolfe4, A. Allen2, V. Picozzi3
  • 1Clovis Oncology, 94158 - San Francisco/US
  • 2Clovis Oncology, Clovis Oncology, 94158 - San Francisco/US
  • 3Pathology, Virginia Mason Medical Center, 98101 - Seattle/US
  • 4Sheraton House, Clovis Oncology UK Ltd, CB30ax - Cambridge/UK

Abstract

Human equilibrative nucleoside transporter 1 (hENT1) is the primary membrane channel through which gemcitabine (GEM) enters pancreatic tumor cells. Patients (pts) whose resected pancreatic ductal adenocarcinoma (PDAC) express low levels of hENT1 may derive little benefit from GEM therapy. Recently, a validated diagnostic immunohistochemistry (IHC) test has been developed. Here, we prospectively test this diagnostic in a series of 204 retrospectively collected formalin-fixed paraffin-embedded (FFPE) PDAC tissues. 134 primary and 70 metastatic PDAC pre-treatment specimens were dichotomized into high versus low hENT1 tumor expression. Overall, 39% of primary and 23% of metastatic cases had high levels of tumoral hENT1. In the primary tumor set 90/134 pts went on to receive GEM-based therapy; pts with high hENT1 tumor levels had a median overall survival (OS) of 35 months compared to 15 months in those with low levels of tumoral hENT1 (HR = 0.48). In 44 non-GEM treated pts there was no association between hENT1 tumor expression and overall survival (median OS of 26 versus 28 months in pts with hENT1 high and low, respectively; HR = 0.8). In 63/70 metastatic specimens from patients treated with GEM the median OS was 25 versus 10 months (HR = 0.64) for high versus low hENT1 tumors respectively. In conclusion, we have prospectively tested the utility of the hENT1 IHC diagnostic in predicting clinical outcome in an institutional series of FFPE tumors from PDAC pts. The assay was effective in identifying GEM-treated pts with a poorer OS outcome using both primary and metastatic FFPE tumor tissues. This diagnostic is being prospectively tested in a global pivotal trial of CO-101 (CP-4126; a lipid drug conjugate of GEM designed to enter tumor cells independently of hENT1) versus GEM alone in metastatic PDAC (“LEAP“, NCT01124786).

Disclosure

M. Raponi: Employee and stock holder of Clovis Oncology.

J. Isaacson: Employee and stock holder of Clovis Oncology.

M. Bartosiewicz: Employee and stock holder of Clovis Oncology.

K. Lin: Employee and stock holder of Clovis Oncology.

L. Rolfe: Employee and stock holder of Clovis Oncology.

A. Allen: Employee and stock holder of Clovis Oncology.

All other authors have declared no conflicts of interest.