Abstract 1297P
Background
GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids, and validated retrospectively (Nicolle et al). The phase 3 PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified FOLFIRINOX (mFFX) over GEM as adjuvant therapy in patients with resected PDAC at the expense of higher toxicity (Conroy et al). We evaluated the potential theranostic value of GemPred in this population.
Methods
Routine formalin fixed paraffin embedded surgical specimen of 350 patients were retrieved for RNA-sequencing and GemPred prediction (167 in Gem arm and 183 in mFFX arm). Survival analyses were stratified by resection margins, lymph-node status and CA19.9 level.
Results
Eighty-nine patients’ tumors (25.5%) were GemPred+ and therefore predicted a theoretical GEM-sensitivity. 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 vs 10 months, HR=0.43; 95%CI [0.29-0.65] p<0.001) and overall survival (OS) (median 68 vs 29 months, HR=0.42; 95%CI [0.27-0.66] p<0.001). GemPred had no predictive value in the mFFX arm. DFS and OS were similar in GemPred+ patients who received adjuvant GEM vs. those receiving mFFX (median 27 versus 24 months, and 68 versus 51 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS (HR=0.44; 95%CI [0.24-0.80]; p=0.008) and OS (HR 0.37; 95%CI [0.19-0.74] p=0.004).
Conclusions
The GemPred signature was positive in a quarter of patients and was associated with a similar survival in the gemcitabine adjuvant group compared to mFFX.
Clinical trial identification
EudraCT 2011-002026-52.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer.
Funding
Institut national du Cancer (INCa), Ligue nationale contre le cancer.
Disclosure
J.L. Iovanna: Financial Interests, Personal, Ownership Interest: PredictingMed. N. Dussetti: Financial Interests, Personal, Ownership Interest: PredictingMed. All other authors have declared no conflicts of interest.