Multicenter phase 3 trial of addition of chemoradiotherapy to chemotherapy for pancreatic head adenocarcinoma

The multicenter phase 3 NRG Oncology/RTOG 0848 trial evaluated whether adding fluoropyrimidine sensitized radiotherapy (CXRT) to adjuvant chemotherapy improves overall survival after curative intent resection among patients with adenocarcioma of the pancreatic head. In the previously reported step 1 of the trial, patients were randomized to gemcitabine versus gemcitabine plus erlotinib. In the now reported step 2, patients without progression after 5 cycles of step 1 chemotherapy were randomized to the 6^th chemotherapy cycle with or without CXRT. A total of 354 patients were randomized (chemotherapy n=174; chemotherapy plus CXRT n=180). The overall survival (OS) primary endpoint was not met (HR 0.96; 90% CI 0.79-1.18). Chemotherapy + CXRT was associated with a trend of improved disease-free survival (DFS; HR 0.82; 95% CI 0.65-1.03) without increase in grade 4-5 toxicities, although with increase in grade 3 toxicities (38% versus 19%; p<0.001). Treatment by nodal status interactions showed that CXRT improved OS (p=0.0063) and DFS (p=0.014) in node negative patients. The authors conclude that overall, addition of CXRT to adjuvant chemotherapy did not statistically significantly improve OS or DFS. Among node negative patients CXRT did improve OS and DFS.