Phase II study of gemcitabine, oxaliplatin in combination with panitumumab in KRAS wild-type unresectable or metastatic biliary tract and gallbladder cancer
BACKGROUND Current data suggest that chemotherapy combinations may be superior to single agents in biliary tract cancer. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan. PATIENTS AND METHODS Patients with advanced (unresectable or metastatic) cholangiocarcinoma, ECOG PS 0-2, and adequate organ function were treated with panitumumab (9 mg/kg) on day 1, and gemcitabine (1000 mg/m(2)) and irinotecan (100 mg/m(2)) on days 1 and 8 of a 21-day cycle. The primary objective was to evaluate the 5-month progression-free survival (PFS). Secondary objectives included overall response rate (ORR) and overall survival (OS). Mutational analyses of EGFR, KRAS and BRAF were carried out when feasible. RESULTS Thirty-five patients received a median of 7 (0-30) cycles. The most common grade 3/4 toxic effects were neutropenia (10 patients, 29%), thrombocytopenia (10 patients, 29%), skin rash (13 patients, 37%) and dehydration (9 patients, 26%). Two patients had CR, 9 had partial response (PR), and 15 had SD for a disease-control rate of 74% (by RECIST) in 28 assessable patients. Two patients went on to have surgical resection. The 5-month PFS was 69%. The median PFS was 9.7 months and the median OS was 12.9 months. In 17 testable samples, no EGFR or BRAF mutations were identified; there were 7 KRAS mutations, with no difference in OS by KRAS status. CONCLUSIONS This study showed encouraging efficacy of this regimen with good tolerability. Further study in this area is warranted. Clinical Trials Number: The trial was registered with the National Cancer Institute (www.clinicaltrials.gov identifier NCT00948935).