Prediction of adjuvant gemcitabine sensitivity in resectable pancreatic adenocarcinoma using the GemPred RNA signature: An ancillary study of the PRODIGE-24/CCTG PA6 clinical trial Journal Article


Authors: Nicolle, R.; Bachet, J. B.; Harlé, A.; Iovanna, J.; Hammel, P.; Rebours, V.; Turpin, A.; Ben Abdelghani, M.; Wei, A.; Mitry, E.; Lopez, A.; Biagi, J.; François, E.; Artru, P.; Lambert, A.; Renouf, D. J.; Monard, L.; Mauduit, M.; Dusetti, N.; Conroy, T.; Cros, J.
Article Title: Prediction of adjuvant gemcitabine sensitivity in resectable pancreatic adenocarcinoma using the GemPred RNA signature: An ancillary study of the PRODIGE-24/CCTG PA6 clinical trial
Abstract: PURPOSEGemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population.PATIENTS AND METHODSRoutine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level.RESULTSEighty-nine patients' tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred- patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P <.001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P <.001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS (P =.008) and CSS (P =.004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P =.001).CONCLUSIONThis ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events. © 2024 American Society of Clinical Oncology.
Keywords: adult; cancer chemotherapy; controlled study; treatment outcome; aged; survival analysis; retrospective studies; major clinical study; genetics; fluorouracil; unspecified side effect; gemcitabine; adjuvant therapy; disease free survival; pancreatic neoplasms; antineoplastic agent; adenocarcinoma; antineoplastic combined chemotherapy protocols; ca 19-9 antigen; retrospective study; irinotecan; rna; cancer specific survival; folinic acid; lymph node; pancreas tumor; pancreas adenocarcinoma; immunological adjuvant; adjuvants, immunologic; oxaliplatin; deoxycytidine; drug sensitivity; predictive value; transcriptome sequencing; surgical margin; humans; human; male; female; article; rna sequencing; doxecitine; gempred rna signature
Journal Title: Journal of Clinical Oncology
Volume: 42
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2024-03-20
Start Page: 1067
End Page: 1076
Language: English
DOI: 10.1200/jco.22.02668
PUBMED: 37963313
PROVIDER: scopus
PMCID: PMC10950182
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Alice Chia-Chi Wei
    197 Wei