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

BACKGROUND 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 AND METHODS Patients were treated with gemcitabine 1000 mg/m(2), oxaliplatin 60 mg/m(2), and panitumumab 6 mg/kg i.v. every 2 weeks followed by two daily administrations of capecitabine 1000 mg/m(2) in 7 days. RESULTS 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. CONCLUSIONS 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.