Immunotherapy success in KRAS G12C adenosquamous pancreatic cancer

“Here, we present a case of metastatic ASCP with a KRAS G12C mutation refractory to multiple lines of systemic therapy, including platinum-based chemotherapy and targeted inhibition of KRAS G12C.”

BUFFALO, NY - November 4, 2024 – A new case report was published in Oncotarget's Volume 15 on October 11, 2024, entitled “A case of adenosquamous pancreatic cancer with a KRAS G12C mutation with an exceptional response to immunotherapy”

This case report highlights a remarkable and unexpected response to immunotherapy in a patient with metastatic adenosquamous pancreatic cancer (ASCP), a rare and aggressive form of pancreatic cancer. The study, led by Murtaza Ahmed, Brent K. Larson, Arsen Osipov, Nilofer Azad, and Andrew Hendifar from Cedars-Sinai Medical Center and Johns Hopkins University, provides new hope for ASCP patients, who are traditionally underserved by current treatment options.

The team documented a 68-year-old male with metastatic ASCP carrying a KRAS G12C mutation. Unexpectedly, after limited success with standard therapies, the patient’s cancer responded significantly to pembrolizumab, a type of immune checkpoint inhibitor, despite the absence of typical markers indicating suitability for immunotherapy.

Pancreatic cancer remains one of the most lethal cancer types, with few advancements in effective treatments for its rarer forms, such as ASCP, which accounts for only 1-10% of all pancreatic cancer cases. Traditionally, ASCP has been treated with chemotherapy based on protocols for the more common pancreatic ductal adenocarcinoma, despite the distinct tumor characteristics.

This case suggests that ASCP’s unique tumor microenvironment may make it more receptive to immunotherapy. Researchers are hopeful that this new understanding will drive clinical trials focused on immunotherapy specifically for ASCP patients, potentially offering new options for those with limited treatment success.

“To that point, there is an active multi-center phase 2 trial investigating outcomes and responses to ICI in patients with metastatic or unresectable ASCP or ampullary cancer.”

In conclusion, this report signals a potential shift in the treatment of rare and aggressive pancreatic cancer subtypes like ASCP. As oncology increasingly embraces personalized medicine, cases like this one open new avenues for patients who were not responsive to traditional therapies, potentially transforming the management of previously intractable cancers.

Continue reading: DOI: https://doi.org/10.18632/oncotarget.28659

Correspondence to: Andrew Hendifar - andrew.hendifar@cshs.org

Keywords: pancreatic cancer, immunotherapy, metastasis

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