Precision medicine for KRAS wild-type pancreatic adenocarcinomas.

Autor: Ben-Ammar I; Gustave Roussy, Département de Médecine, 94800 Villejuif, France; Sorbonne Université, Faculté de Médecine, 75005 Paris, France., Rousseau A; Gustave Roussy, Département de Médecine, 94800 Villejuif, France; Oncostat INSERM U1018, Gustave Roussy, Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Département de Biostatistiques et D'épidémiologie, Université Paris-Saclay, Villejuif, France., Nicolle R; Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Université Paris Cité, Paris, France., Tarabay A; Gustave Roussy, Département de Médecine, 94800 Villejuif, France., Boige V; Gustave Roussy, Département de Médecine, 94800 Villejuif, France., Valery M; Gustave Roussy, Département de Médecine, 94800 Villejuif, France., Pudlarz T; Gustave Roussy, Département de Médecine, 94800 Villejuif, France., Malka D; Gustave Roussy, Département de Médecine, 94800 Villejuif, France., Gelli M; Gustave Roussy, Département de Chirurgie, 94800 Villejuif, France., Fernandez-De-Sevilla E; Gustave Roussy, Département de Chirurgie, 94800 Villejuif, France., Fuerea A; Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Université Paris Cité, Paris, France., Tanguy ML; Gustave Roussy, Département de Biostatistiques et D'épidémiologie, Université Paris-Saclay, Villejuif, France., Rouleau E; Gustave Roussy, Département de Génétique Médicale, 94800 Villejuif, France., Barbe R; Gustave Roussy, Département de Radiologie, 94800 Villejuif, France., Mathieu JRR; INSERM U1279, Gustave Roussy, 94800 Villejuif, France., Jaulin F; INSERM U1279, Gustave Roussy, 94800 Villejuif, France; Université Paris Saclay, 91471 Orsay, France., Smolenschi C; Gustave Roussy, Département de Médecine, 94800 Villejuif, France; Gustave Roussy, DITEP, 94800 Villejuif, France., Hollebecque A; Gustave Roussy, Département de Médecine, 94800 Villejuif, France; Gustave Roussy, DITEP, 94800 Villejuif, France., Ducreux M; Gustave Roussy, Département de Médecine, 94800 Villejuif, France; INSERM U1279, Gustave Roussy, 94800 Villejuif, France; Université Paris Saclay, 91471 Orsay, France., Boileve A; Gustave Roussy, Département de Médecine, 94800 Villejuif, France; INSERM U1279, Gustave Roussy, 94800 Villejuif, France; Université Paris Saclay, 91471 Orsay, France. Electronic address: Alice.boileve@gustaveroussy.fr.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 Jan; Vol. 197, pp. 113497. Date of Electronic Publication: 2023 Dec 15.
DOI: 10.1016/j.ejca.2023.113497
Abstrakt: Background: KRAS mutation is the most common molecular alteration in pancreatic adenocarcinoma (PDAC), and around 10% of patients harbor KRAS wild-type tumors (KRAS WT ).
Methods: A retrospective chart review of clinical/molecular data was performed including all PDAC patients with a determined KRAS status (tumor molecular profiling on tissue or liquid biopsy).
Results: 342 patients were included with 54 KRAS WT PDAC (16%) compared to 288 patients with KRAS m PDAC. Median age was 61 years [IQR:54.0;67.0] and 164 pts (48%) were female. At diagnosis, KRAS WT patients (63%) were more frequently diagnosed at a non-metastatic stage compared to KRAS m patients (41%) (p = 0.003). Regarding metastatic sites, liver was less frequent in KRAS WT (39%, p < 0.0001). Median overall survival (mOS) from initial diagnosis was significantly higher in the KRAS WT group compared to KRAS m (50.8 months, CI95% [32.0-NR] vs 21.1 months, CI95% [18.9-23.4] (p < 0.004 after adjustment on age, ECOG and stage at diagnosis). In first-line systemic treatment, (mostly FOLFIRINOX) progression-free survival (PFS) was also higher in KRAS WT . Based on ESCAT classification, a putative actionable alteration (ESCAT I-III) was identified in 19 (36%) KRAS WT pts and 46 (16%) KRAS m patients (p < 0.0001) with more alterations in FGFR2, BRAF(V600E), NRTK and more MSI tumors. KRAS WT harbored also fewer alterations in TP53, CDKN2A, and SMAD4. 12 KRAS WT patients received a molecularly-matched treatment with clinical benefit and improved outcomes compared to KRAS m patients.
Conclusions: KRAS WT patients display distinct disease characteristics and outcomes with prolonged overall survival. KRAS WT patients also harbor more actionable molecular alterations, leading to higher survival rates after receiving molecularly matched treatments.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Antoine Hollebecque: Amgen, AstraZeneca, Debiopharm, Eli Lilly and Company, Incyte Corporation, QED Therapeutics. David Malka: Roche, Amgen, Bayer, Sanofi, Merck Serono, Servier, Sanofi, Pierre Fabre, Viatris, Bristol Myers Squibb, MSD Oncology, LEO Pharma, Incyte, AstraZeneca, Taiho Oncology, Pfizer. Fanny Jaulin: ORAKL. Valérie Boige: Amgen, AstraZeneca, Bayer Schering Pharma, Ipsen, Merck Serono, MSD Oncology, Roche/Genentech. Michel Ducreux: Merck Serono, MSD, AMGEN, Roche, Bayer, Ipsen, Pfizer, Servier, Pierre Fabre, HalioDx, Lilly, Sanofi, BMS. Alice Boilève: Merck Serono, Ipsen. Other authors report no conflict of interest.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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