Sequential neoadjuvant chemoradiotherapy (CRT) followed by curative surgery vs. primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma: NEOPA- a randomized multicenter phase III study (NCT01900327, DRKS00003893, ISRCTN82191749)

Abstract

BackgroundMedian OS after surgery in curative intent for non-metastasized pancreas cancer ranges under study conditions from 17.9 months to 23.6 months. Tumor recurrence occurs locally, at distant sites (liver, peritoneum, lungs), or both. Observational and autopsy series report local recurrence rates of up to 87% even after potentially “curative” R0 resection. To achieve better local control, neoadjuvant CRT has been suggested for preoperative tumour downsizing, to elevate the likelihood of curative, margin-negative R0 resection and to increase the OS rate. However, controlled, randomized trials addressing the impact of neoadjuvant CRT survival do not exist.Methods/DesignThe underlying hypothesis of this randomized, two-armed, open-label, multicenter, phase III trial is that neoadjuvant CRT increases the three-year overall survival by 12% compared to patients undergoing upfront surgery for resectable pancreatic cancer. A rigorous, standardized technique of histopathologically handling Whipple specimens will be applied at all participating centers. Overall, 410 patients (n = 205 in each study arm) will be enrolled in the trial, taking into regard an expected drop out rate of 7% and allocated either to receive neoadjuvant CRT prior to surgery or to undergo surgery alone. Circumferential resection margin status, i.e. R0 and R1 rates, respectively, surgical resectability rate, local and distant disease-free and global survival, and first site of tumor recurrence constitute further essential endpoints of the trial.DiscussionFor the first time, the NEOPA study investigates the impact of neoadjuvant CRT on survival of resectable pancreas head cancer in a prospectively randomized manner. The results of the study have the potential to change substantially the treatment regimen of pancreas cancer.Trial registrationClinical Trial gov: NCT01900327, DRKS00003893, ISRCTN82191749

Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

“…Clinical trials to assess outcomes for specific regimens in the neoadjuvant setting are currently recruiting, such as the phase III NEOPA trial, which is comparing neoadjuvant gemcitabine chemoRT therapy to upfront surgery (ClinicalTrials. gov identifier: NCT01900327), 168 and the randomized phase II SWOG 1505 trial, which is intended to establish benchmarking data for fluorouracil, irinotecan, and oxaliplatin and gemcitabine and albumin-bound paclitaxel (NCT02562716). Currently, the panel does not recommend neoadjuvant therapy for clearly resectable patients without highrisk features, except in a clinical trial.…”

Neoadjuvant treatment for resectable pancreatic adenocarcinoma: What is the best protocol?

“…Two cycles of the GS regimen, which was used in the Prep‐02/JSAP05 study, have been a standard regimen for NAC, at least in Japan, for potentially resectable PDAC . Although several prospective trials using other regimens, which include radiotherapy, are ongoing, their results have yet been clearly reported . Considering recent progress in chemotherapy for UR PDAC, a clinical question has been raised about the optimal protocol in the neoadjuvant setting.…”

Neoadjuvant Therapy for Pancreatic Cancer

“…15 Phase III trials addressing these issues are in progress. 16 In this article, we review prospective phase II trials of neoadjuvant chemotherapy/CRT and discuss associated postoperative morbidities and mortalities. We further assess whether neoadjuvant chemotherapy/CRT cause increased or similar postoperative complications and mortality as compared with existing surgical data.…”