Durable Response to Sotorasib in KRAS G12C -Mutant Intrahepatic Cholangiocarcinoma: A Case Report

KRAS G12C mutations are rare in intrahepatic cholangiocarcinoma (iCCA), occurring in approximately 1% of cases. While adagrasib has shown efficacy in biliary tract cancers in clinical trials, real-world evidence for sotorasib remains limited. We report a 64-year-old male with advanced iCCA harboring a KRAS p.(G12C) mutation (58.07% allelic frequency) who progressed on multiple prior therapies including chemotherapy, immunotherapy, and targeted therapy. Disease progression was complicated by obstructive jaundice and ECOG performance status deterioration to 3, requiring percutaneous transhepatic cholangiodrainage (PTCD). Following initiation of sotorasib 480 mg daily, the patient achieved a marked partial radiographic response within 6 weeks. CA19-9 normalized, jaundice resolved, PTCD was removed, and performance status improved to ECOG 1. The patient received continuous sotorasib for 10 months, with the initial partial response lasting 8 months with no significant treatment-related adverse events. This case provides real-world evidence that sotorasib can induce durable responses in chemotherapy-refractory, KRAS G12C-mutant iCCA, including in patients with poor performance status and obstructive jaundice who would typically be excluded from clinical trials.