Prediction of adjuvant gemcitabine sensitivity in resectable pancreatic ductal adenocarcinoma using the GemPred RNA signature

GemPred, a RNA signature predictive of the efficacy of adjuvant gemcitabine (GEM) in pancreatic ductal adenocarcinoma (PDAC), was developed from cell lines and organoids and has been validated retrospectively. The phase 3 PA6 trial in France has demonstrated the superiority of adjuvant mFOLFIRINOX over GEM as adjuvant therapy in patients with resected PDAC at the expense of higher toxicity. RNA sequencing analysis of surgical specimens showed that 25.5% of the patients were GemPred+ and were thus predicted to be gemcitabine sensitive. The figure shows that in the GEM arm, GemPred+ patients had significantly longer disease-free and cancer-specific survival than GemPred- patients, while GemPred had no prognostic value in the mFOLFIRINOX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM versus mFOLFIRINOX. GemPred+ patients had significantly more grade ≥ 3 adverse events with mFOLFIRINOX than with GEM. The authors conclude that GemPred status predicted adjuvant gemcitabine sensitivity after resection of PDAC.