Case Presentation: KRAS-Targeted Therapy in Metastatic Pancreatic Ductal Adenocarcinoma
Patient Case:
A 66-year-old woman presented with a 6-month history of unintentional weight loss of approximately 20 pounds, mild fatigue, and postprandial epigastric pain radiating to the back. The pain progressively worsened over time and frequently awakened her at night. She presented to the emergency department for pain control, where a CT scan of the abdomen and pelvis revealed a 5 cm pancreatic mass with multiple hepatic lesions, the largest measuring 4.5 cm in diameter. Of note her only past medical history is a recent diagnosis of diabetes mellitus currently well controlled on metformin.
Laboratory studies were within normal limits except for an elevated alkaline phosphatase level and a markedly elevated CA 19-9 of 3,543 U/mL. She was admitted for pain management and further evaluation. A biopsy of one of the liver lesions demonstrated moderately differentiated adenocarcinoma. Immunohistochemistry (IHC) was positive for CK7 and CK19 and negative for CK20, findings consistent with a pancreatic primary tumor. Her pain was adequately controlled during hospitalization, and she was discharged to the medical oncology clinic for further management.
At follow-up, a CT scan of the chest demonstrated no evidence of thoracic metastases. Her family history was notable for pancreatic cancer in a paternal uncle diagnosed at age 72. Germline genetic testing was performed according to standard protocol and revealed no pathogenic variants. The liver biopsy specimen underwent next-generation sequencing (NGS), which identified TP53 and KRAS G12C mutations. Tumor mutational burden (TMB) was low, and the tumor was microsatellite stable (MSS). Her Eastern Cooperative Oncology Group (ECOG) performance status was 1 at the time of treatment initiation.
She was started on biweekly gemcitabine and nab-paclitaxel, which she tolerated well. After one month of therapy, she had gained 5 pounds, reported improved appetite, and her ECOG performance status improved to 0. Repeat CT imaging of the abdomen and pelvis demonstrated a significant reduction in the size of the hepatic lesions and slight improvement in the primary pancreatic mass. Her CA 19-9 level decreased to 57 U/mL, consistent with a robust treatment response.
She maintained disease control for approximately 12 months before experiencing progression, with new hepatic lesions and growth of previously identified metastases. At that time, she expressed a preference not to pursue additional cytotoxic chemotherapy and inquired about potential targeted therapeutic options.
