Somatic Mutation Profile as a Predictor of Treatment Response and Survival in Unresectable Pancreatic Ductal Adenocarcinoma Treated with FOLFIRINOX and Gemcitabine Nab-Paclitaxel

• Published in: Cancers Vol. 16; no. 15; p. 2734
• Main Authors: Paredes de la Fuente, Rodrigo, Sucre, Santiago, Ponce, Cristina, Rattani, Ahmed Anwer Ali, Peters, Mary Linton B
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2024
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenocarcinoma; Cancer; Cancer patients; Cancer therapies; Cell cycle; Chemotherapy; Cytotoxicity; Decision making; Development and progression; Gemcitabine; Gene mutations; Genetic aspects; Mutation; Next-generation sequencing; Oncology; Oncology, Experimental; Paclitaxel; Pancreatic cancer; Patient outcomes; Patients; Precision medicine; Survival; Survival analysis; Tumors; precision oncology; chemotherapy; treatment response; molecular profiling; pancreatic ductal adenocarcinoma
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16152734

(1) Background: Pancreatic ductal adenocarcinoma (PDAC) has low survival rates despite treatment advancements. Aim: This study aims to show how molecular profiling could possibly guide personalized treatment strategies, which may help improve survival outcomes in patients with PDAC. (2) Materials and Methods: A retrospective analysis of 142 PDAC patients from a single academic center was conducted. Patients underwent chemotherapy and next-generation sequencing for molecular profiling. Key oncogenic pathways were identified using the Reactome pathway database. Survival analysis was performed using Kaplan-Meier curves and Cox Proportional Hazards Regression. (3) Results: Patients mainly received FOLFIRINOX (n = 62) or gemcitabine nab-paclitaxel (n = 62) as initial chemotherapy. The median OS was 13.6 months. Longer median OS was noted in patients with NOTCH (15 vs. 12.3 months, = 0.007) and KIT pathway mutations (21.3 vs. 12.12 months, = 0.04). Combinatorial pathway analysis indicated potential synergistic effects on survival. In the PFS, PI3K pathway (6.6 vs. 5.7 months, = 0.03) and KIT pathway (10.3 vs. 6.2 months, = 0.03) mutations correlated with improved PFS within the gemcitabine nab-paclitaxel subgroup. (4) Conclusions: Molecular profiling could play a role in PDAC for predicting outcomes and responses to therapies like FOLFIRINOX and gemcitabine nab-paclitaxel. Integrating genomic data into clinical decision-making can benefit PDAC treatment, though further validation is needed to fully utilize precision oncology in PDAC management.