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

Author(s) :

Nicolle, Rémy [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Bachet, Jean-Baptiste [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Harlé, Alexandre [Auteur]
Centre de Recherche en Automatique de Nancy [CRAN]
Iovanna, Juan [Auteur]
Centre de Recherche en Cancérologie de Marseille [CRCM]
Hammel, Pascal [Auteur]
Hôpital Paul Brousse
Rebours, Vinciane [Auteur]
Hôpital Beaujon [AP-HP]
Turpin, Anthony [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Ben Abdelghani, Meher [Auteur]
Institut de Cancérologie de Strasbourg Europe [ICANS]
Wei, Alice [Auteur]
Memorial Sloane Kettering Cancer Center [New York]
Mitry, Emmanuel [Auteur]
Institut Paoli-Calmettes [IPC]
Lopez, Anthony [Auteur]
Service d'Hépato-gastro-entérologie [CHRU Nancy]
Biagi, James [Auteur]
Queen's University [Kingston, Canada]
François, Eric [Auteur]
Hôpital privé Jean Mermoz [Lyon]
Artru, Pascal [Auteur]
Adaptation, mesure et évaluation en santé. Approches interdisciplinaires [APEMAC]
Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL]
Lambert, Aurélien [Auteur]
Adaptation, mesure et évaluation en santé. Approches interdisciplinaires [APEMAC]
Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL]
Renouf, Daniel [Auteur]
BC Cancer Agency [BCCRC]
University of British Columbia [Canada] [UBC]
Monard, Laure [Auteur]
UNICANCER
Mauduit, Marjorie [Auteur]
UNICANCER
Dusetti, Nelson [Auteur]
Centre de Recherche en Cancérologie de Marseille [CRCM]
Institut Paoli-Calmettes [IPC]
Conroy, Thierry [Auteur]
Adaptation, mesure et évaluation en santé. Approches interdisciplinaires [APEMAC]
Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL]
Cros, Jérome [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Hôpital Beaujon [AP-HP]

Journal title :

Journal of Clinical Oncology

Pages :

1067-1076

Publisher :

American Society of Clinical Oncology

Publication date :

2023-11-14

ISSN :

0732-183X

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer

English abstract : [en]

PURPOSE: GemPred, 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 ...
Show more >PURPOSE: GemPred, 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 METHODS: Routine 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. RESULTS: Eighty-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). CONCLUSION: This 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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL