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MEK inhibitor–based genomically matched combinatorial targeted therapies in metastatic pancreatic adenocarcinoma with KRAS alterations

Year: 2026

Type: article

Abstract: 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 and 2024. RESULTS: Ten patients had KRAS G12R (34.5%), ten G12D (34.5%), and nine G12V (31%). The 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 = .5), respectively, and median progression-free survival was 4.4/2.3/1.4 months (P = .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.

Source: The Oncologist

DOI: 10.1093/oncolo/oyag040