MEK inhibitor-based genomically matched combinatorial targeted therapies in metastatic pancreatic adenocarcinoma with KRAS alterations. Oncologist 2026 Feb 17
Date
02/17/2026Pubmed ID
41701177DOI
10.1093/oncolo/oyag040Abstract
INTRODUCTION: Pancreatic Ductal Adenocarcinoma (PDAC) is often caused by mutations in multiple genes including KRAS (activating the Ras-Raf-MEK-ERK pathway). This study evaluated the role of MEK inhibitor (MEKi)-based combinatorial targeted therapies in patients with PDAC. Methods. This is a retrospective/prospective observational, single institution study, including 29 patients with metastatic PDAC with KRAS alterations, treated with MEKi therapies between 2022-2024.
RESULTS: Ten patients had KRAS G12R (34.5%), ten G12D (34.5%), and nine G12V (31%). Majority of patients received MEKi therapy as third-line and beyond (KRAS G12R/G12D/G12V 60%/50%/78%, respectively). Median overall survival from MEKi initiation for KRAS G12R/G12D/G12V was 8.2/5.1/4.7 months (P = 0.5), respectively, and median progression-free survival was 4.4/2.3/1.4 months (P = 0.11). Six (21%) patients discontinued at least one drug in the treatment combination due to toxicity.
CONCLUSIONS: MEKi-based combinatorial therapies had modest disease control in patients with KRAS G12R, and minimal disease control in patients with KRAS G12D/V in the late-line setting.
Author List
Auckley ED, Yohay S, Ying G, Szabo A, Wittmann J, Grahl J, Aldakkak M, Thalji SZ, McFall T, Kurzrock R, George B, Kamgar MAuthors
Mandana Kamgar MPH, MD Associate Professor in the Medicine department at Medical College of WisconsinAniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin
