Abstract IA27: Clinical trials in locally advanced pancreatic cancer (LAPC)
Authors: Crane Christopher H. 
Published: October 2015

Abstract
The role of radiation in locally advanced unresectable pancreatic cancer (LAPC) is more controversial now that ever. Perhaps the greatest impact on clinical practice in LAPC has come from the LAP07 trial, which evaluated the addition of erlotinib to gemcitabine and the role of consolitative chemoradiation. Results from the trial were presented at ASCO last year and showed no benefit to the use of consolidative chemoradiation after 4 months of gemcitabine based chemotherapy compared to 6 months of chemotherapy alone. Issues regarding the off protocol use of chemoradiation, compliance in the chemoradiation arm, and XRT quality assurance require further clarity. The publication of the full manuscript from the trial is expected this year. Two prior phase III trials comparing initial chemotherapy to initial chemoradiation have reported conflicting results. The Fédération Francophone de Cancérologie Digestive and Société Française de Radiothérapie Oncologique (FFCD-SFRO) showed superior survival of gemcitabine alone to a poorly tolerated experimental chemoradiation regimen (60 Gy to large fields with cisplatin and 5FU) that had not been tested in a phase I or II trial. The only other recent trial to compare initial chemotherapy to chemoradiation was conducted by the Eastern Cooperative Oncology Group (ECOG 4201). This trial compared gemcitabine-based chemoradiation followed by weekly gemcitabine to gemcitabine alone. A median survival benefit was seen in the chemoradiation arm. This benefit came at the cost of increased gastrointestinal toxicity. A number of U. S. cooperative group trials evaluating gemcitabine-based chemotherapy in advanced pancreatic cancer have included patients with locally advanced disease without planned radiotherapy. Median survival durations of between 9.1 and 9.9 months have been achieved in these subsets of patients, compared to between 12 and 14.3 months in the LAP07 and FFCD-SFRO trials. The reason for this difference is unclear.
The rationale for the further study of the use of radiation therapy in locally advanced unresectable pancreatic cancer (LAPC) is based on clinical and autopsy data which indicate that 30% or more of patients die with disease confined to the primary site. Local tumor control rates at one year are commonly reported to be greater than 90%, but have fallen to below 50% at 2 years in studies that have reported longer median OS. As median survival durations improve in patients with locally advanced pancreatic cancer, local progression of disease will probably be revealed to more commonly limit long-term survival. RTOG 1201 is a randomized phase II trial that will address this limitation. It compares gemcitabine and abraxane alone to gemcitabine and abraxane followed by standard or high dose radiation using IMRT. It will also address the role of the use SMAD4 expression to predict the pattern of disease progression.
Citation Format: Christopher H. Crane. Clinical trials in locally advanced pancreatic cancer (LAPC). [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr IA27.