Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer

• Published in: Annals of oncology Vol. 23; no. 9; pp. 2341 - 2346
• Main Authors: Jensen, L.H., Lindebjerg, J., Ploen, J., Hansen, T.F., Jakobsen, A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-09-2012; Oxford University Press
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; biliary tract cancer; Biliary Tract Neoplasms - drug therapy; Biliary Tract Neoplasms - metabolism; Biliary Tract Neoplasms - mortality; Biological and medical sciences; Biomarkers, Tumor - metabolism; Capecitabine; chemotherapy; cholangiocarcinoma; Cholangiocarcinoma - drug therapy; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - mortality; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease-Free Survival; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - metabolism; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gastroenterology. Liver. Pancreas. Abdomen; Gemcitabine; Humans; Kaplan-Meier Estimate; KRAS; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; marker-driven treatment; Medical sciences; Middle Aged; Organoplatinum Compounds - administration & dosage; Oxaliplatin; Panitumumab; Pharmacology. Drug treatments; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Statistics, Nonparametric; Treatment Outcome; Tumors; biliary tract cancer; marker-driven treatment; KRAS; panitumumab; chemotherapy; cholangiocarcinoma; Antineoplastic agent; Bile duct cancer; Panitumumab; Biological marker; Hepatic disease; Monoclonal antibody; Malignant tumor; Biliary tract disease; Wild type; Epidermal growth factor receptor; K ras Gene; Chemotherapy; Treatment; Malignant cholangioma; C-Onc gene; Phase II trial; Digestive diseases; Clinical trial; Protooncogene; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mds008

Combination chemotherapy has proven beneficial in biliary tract cancer and further improvements may be achieved by individualizing treatment based on biomarkers and by adding biological agents. We report the effect of chemotherapy with panitumumab as first-line therapy for KRAS wild-type irresectable biliary tract cancer.
Patients were treated with gemcitabine 1000 mg/m2, oxaliplatin 60 mg/m2, and panitumumab 6 mg/kg i.v. every 2 weeks followed by two daily administrations of capecitabine 1000 mg/m2 in 7 days.
During 22 months, 46 patients were included in a single institution. The primary end point, fraction of progression-free survival (PFS) at 6 months, was 31/42 [74%; 95% confidence interval (CI) 58% to 84%]. Forty-two patients had measurable disease. Response rate was 33% and disease control rate 86%. Median PFS was 8.3 months (95% CI 6.7–8.7 months) and median overall survival was 10.0 months (95% CI 7.4–12.7 months). Toxicity was manageable including eight cases of epidermal growth factor receptor-related skin adverse events of grade 2 or more.
Marker-driven patient selection is feasible in the systemic treatment of biliary tract cancer. Combination chemotherapy with panitumumab in patients with KRAS wild-type tumors met the efficacy criteria for future testing in a randomized trial.