An interim evaluation of efficacy and safety of the combination of panitumumab, gemcitabine, and irinotecan in patients with advanced or metastatic cholangiocarcinoma: A phase II study

328 Background: Cholangiocarcinoma is an aggressive neoplasm. Current chemotherapy approaches suggest that combinations may be superior to single agents in this disease. Over-expression of epidermal growth factor receptor (EGFR) is associated with tumor stage and prognosis. This study was designed to evaluate the efficacy and tolerability of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan in patients with advanced and metastatic cholangiocarcinoma. Methods: Pts with advanced unresectable or metastatic cholangiocarcinoma, ECOG PS 0-2, and adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, gemcitabine (1000 mg/m2/100 min) iv and irinotecan (100 mg/m2) iv on days 1 and 8 of a 21-day cycle. Tissue specimens were collected based on availability for future biomarker analyses. The primary objective was to evaluate the 5-month progression-free survival (PFS) rate. The secondary objectives include overall response rate (ORR), overall survival rate (OS) and toxicity of the combination. Results: There have been 24 (of planned 42) pts recruited to the study. Toxicity of the combination was assessed in all enrolled pts. There were no treatment related deaths. The most common gr 3 or higher toxicity was were neutropenia (10 pts [40%]), thrombocytopenia (6 pts, [25%]), skin rash (4 pts [17%]) and diarrhea (3 pts, [12%]). One pt developed a gr 2 infusion reaction, which was considered related to panitumumab. Efficacy was evaluated in 20 pts. Among them, there were 2 CR, 6 PR, and 10 SD (with disease control rate of 90%), and 2 PD (assessed by RECIST criteria). Two pts went on to have surgical resection. Eight pts had ≥ 10 cycles of the therapy, and dose modification/interruption were needed for some of these pts. Conclusions: The data of this on-going study showed encouraging results of the combination of panitumumab with gemcitabine and irinotecan in both tolerability and efficacy. The pre-specified efficacy criteria to continue enrollment were met. Further analysis by biomarker status (KRAS/BRAF/EGFR) is forthcoming.