Long-term outcomes of a multinational phase 3 trial of adjuvant gemcitabine with or without capecitabine for pancreatic ductal adenocarcinoma

The multinational phase 3 ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) for pancreatic ductal adenocarcinoma (PDAC) resulted in longer overall survival than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival with mFOLFIRINOX but had more restrictive eligibility criteria. Long-term follow-up of ESPAC4 has now been published. After a median follow-up of 104 months, the median overall survival was significantly longer with GemCap than with gemcitabine; this difference was driven by patients who underwent R0-resection. Lymph node-negative patients, but not lymph node-positive patients, had longer overall survival with GemCap than with gemcitabine. Among the ESPAC patients who would not have been eligible for PRODRIGE24, the median survival was significantly longer with GemCap than with gemcitabine. The authors conclude that adjuvant GemCap is a standard option for PDAC patients not eligible for mFOLFIRINOX. Exploratory evidence suggests that GemCap may be particularly efficacious in R0 patients and lymph node-negative patients.