Precision medicine for KRAS wild-type pancreatic adenocarcinomas.
Eur J Cancer
; 197: 113497, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38134480
ABSTRACT
BACKGROUND:
KRAS mutation is the most common molecular alteration in pancreatic adenocarcinoma (PDAC), and around 10% of patients harbor KRAS wild-type tumors (KRASWT).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 KRASWT PDAC (16%) compared to 288 patients with KRASm PDAC. Median age was 61 years [IQR54.0;67.0] and 164 pts (48%) were female. At diagnosis, KRASWT patients (63%) were more frequently diagnosed at a non-metastatic stage compared to KRASm patients (41%) (p = 0.003). Regarding metastatic sites, liver was less frequent in KRASWT (39%, p < 0.0001). Median overall survival (mOS) from initial diagnosis was significantly higher in the KRASWT group compared to KRASm (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 KRASWT. Based on ESCAT classification, a putative actionable alteration (ESCAT I-III) was identified in 19 (36%) KRASWT pts and 46 (16%) KRASm patients (p < 0.0001) with more alterations in FGFR2, BRAF(V600E), NRTK and more MSI tumors. KRASWT harbored also fewer alterations in TP53, CDKN2A, and SMAD4. 12 KRASWT patients received a molecularly-matched treatment with clinical benefit and improved outcomes compared to KRASm patients.CONCLUSIONS:
KRASWT patients display distinct disease characteristics and outcomes with prolonged overall survival. KRASWT patients also harbor more actionable molecular alterations, leading to higher survival rates after receiving molecularly matched treatments.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Adenocarcinoma
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Carcinoma Ductal Pancreático
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França