Treatment strategy for locally advanced pancreatic cancer

Abstract

Systemic chemotherapy (CT) is the mainstay of treatment for unresectable pancreatic cancer (PC). Gemcitabine (GEM) has been the standard of care for more than a decade. Chemoradiotherapy (CRT) is also a treatment option for patients (pts) with locally advanced PC (LAPC), and “induction CT followed by CRT” is recognized as one potentially promising strategy. Retrospective analysis of GERCOR phase II and III studies demonstrated significantly better progression-free survival (PFS) and overall survival (OS) in pts without tumor progression during 3 months of initial CT who were subsequently treated with CRT compared to continuing CT alone. The GERCOR LAP07 phase III study did not show a survival benefit with CRT compared to CT alone in pts with controlled disease after 4 months of induction CT, but there was a trend towards improved PFS, a significant local control benefit, and a significantly prolonged treatment-free interval in the CRT arm. In Japan, randomized phase II study was conducted to evaluate the efficacy and safety of CRT with and without induction CT (JCOG1106). LAPC pts were randomized to CRT (Arm A) or induction CT followed by CRT (Arm B). Pts in Arm A received CRT with S-1. Pts in Arm B received induction GEM for 12 weeks and only pts with controlled disease received same CRT as Arm A. After CRT, GEM was continued until disease progression in both arms. In the final analysis, 2-year OS for Arm A/B were 36.9/18.9% (HR 1.26 [95%CI 0.82-1.93]). Compared to CRT alone, induction GEM followed by CRT was less toxic, but not considered a promising regimen because of a poorer long-time survival. Recently, FOLFIRINOX and GEM/nab-paclitaxel (GnP) were reported to improve survival compared to GEM alone in the metastatic setting, and these regimens are also being increasingly used for LAPC pts. JCOG has started a randomized phase II study of modified FOLFIRINOX vs. GnP to select more promising CT regimen for subsequent phase III study comparing with CRT (JCOG1407).