P-164 - Gemcitabine versus FOLFIRINOX in patients with advanced pancreatic adenocarcinoma HENT1 positive: back to the future

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Pancreatic Cancer
Presenter M.A. Calegari
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors M.A. Calegari1, A. Cassano1, M. Basso1, C. Barone2, A. Orlandi1, A. Cocomazzi3, M. Martini3, C. Bagala1, G. Indellicati1, V. Zurlo1, S. Monterisi1, C. Di Dio1, R. Barile1, M.A. Di Salvatore1, L.M. Larocca3
  • 1Università Cattolica del Sacro Cuore - Oncologia Medica, Rome/IT
  • 2Catholic University of Sacred Heart - Rome, Rome/IT
  • 3Università Cattolica del Sacro Cuore - Anatomia Patologica, Rome/IT

Abstract

Introduction

Human equilibrative nucleoside transporter 1 (hENT1) is a transmembrane protein which acts as a nucleoside transporter and is the main mediator of gemcitabine (GEM) uptake into human cells. Several studies showed a positive predictive role of hENT1 expression in adjuvant pancreatic adenocarcinoma (PAC) treated with GEM. In this retrospective study we compared GEM versus FOLFIRINOX (a more effective and toxic regimen) in a series of patients affected by metastatic PAC (m-PAC) in which hENT1 evaluation was available.

Methods

149 patients affected by histologically confirmed unresectable locally advanced- or m-PAC, treated in our institution from 2009 to 2013, have been screened for inclusion in this retrospective study. 70 patients, treated with GEM or FOLFIRINOX in first-line therapy, fulfilled clinical inclusion criteria for survival analysis. 31 patients, whose stored tumor samples were available and contained sufficient quality/quantity DNA for evaluation of hENT1 expression by RT-PCR, underwent this exploratory analysis. The primary endpoint was OS and the secondary endpoint was PFS. Safety was assessed in terms of grade 3-4 adverse events (AEs).

Results

The survival analysis, carried out on 70 patients regardless of hENT1 expression, showed a longer OS (11 vs 8 months; HR 0.66, 95% CI: 0.34-0.9; p = 0.03) and PFS (6 vs 3 months; HR 0.76, 95% CI: 0.38-1.25; p = 0.1) in the group treated with FOLFIRINOX compared to GEM. The incidence of hematologic and non hematologic -G3-4 AEs was also higher in the FOLFIRINOX group. Within the exploratory analysis, which included 31 patients, no differences were found in hENT1 positive (hENT1 + ve) patients treated with FOLFIRINOX compared to GEM in terms of OS (8.5 vs 7 months, HR: 0.89; 95% CI: 0.3-2.5; p = 0.8) and PFS (5.5 vs 5 months, HR: 0.8, CI 95%: 0.2-2.2; p = 0.61). GEM-treated hENT1 + ve patients showed a statistically significant improvement both of OS (8 vs 2 months; p = 0.0012) and PFS (5 vs 1 months; p = 0.0004) in comparison to GEM-treated hENT1 negative (hENT1-ve) patients. On the contrary, FOLFIRINOX-treated hENT1 + ve patients had OS and PFS similar to FOLFIRINOX-treated hENT1-ve patients.

Conclusion

In our exploratory analysis GEM seems as effective as FOLFIRINOX in terms of survival with a better safety profile in hENT1 + ve m-PAC. Whether confirmed in prospective studies, GEM monotherapy or GEM-based therapy might be the standard first-line regimen in this selected population.