A case of adenosquamous pancreatic cancer with a KRAS G12C mutation with an exceptional response to immunotherapy

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// Murtaza Ahmed 1 , Brent K. Larson 2 , Arsen Osipov 3 , Nilofer Azad 4 and Andrew Hendifar 3 1 Department of Internal Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA 2 Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA 3 Department of Internal Medicine (Division of Hematology-Oncology) Cedars Sinai Medical Center, Los Angeles, CA 90048, USA 4 Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21218, USA Correspondence to: Andrew Hendifar, email: andrew.hendifar@cshs.org Keywords: pancreatic cancer; immunotherapy; metastasis Received: May 29, 2024 Accepted: September 17, 2024 Published: October 11, 2024 Copyright: © 2024 Ahmed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths, with adenosquamous carcinoma of the pancreas (ASCP), a rare variant, representing 1–10% of cases. Standard chemotherapy trials for pancreatic cancer exclude ASCP, leaving its optimal treatment uncertain. This report describes a 68-year-old male with metastatic ASCP and a KRAS G12C mutation, progressing through multiple lines of systemic therapy, including targeted inhibition of KRAS G12C. Notably, the patient exhibited a robust response to single-agent immune checkpoint inhibition (ICI) with pembrolizumab, despite intact mismatch repair proteins. The limited success of traditional therapies in pancreatic cancer, coupled with the rarity of ASCP, presents a challenge in establishing effective treatment strategies. While KRAS G12C inhibitors demonstrated modest benefits, this case highlights the remarkable response to ICI in a patient with squamous histology. The distinct tumor microenvironment of ASCP, characterized by squamous differentiation, may contribute to this exceptional response. This underscores the need for further research and clinical trials focused on ICI in ASCP, with an ongoing multi-center phase 2 trial investigating outcomes in this specific subset.

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