Phase II study of irinotecan plus panitumumab as second-line therapy for patients with advanced esophageal adenocarcinoma (EAC).

Abstract

TPS206 Background: Esophageal carcinoma is highly lethal and the incidence is increasing, especially the subtype of EAC. Our group demonstrated that overexpression of the epidermal growth factor receptor (EGFR) correlates with lower survival in EAC. Panitumumab (P) is a high affinity fully human IgG2 monoclonal antibody directed against human EGFR. Cetuximab combined with irinotecan (I) is effective for second-line treatment of advanced colorectal cancer (CRC). P alone is active in EGFR expressing CRC. Our group has empiric evidence for the activity of cetuximab + I. As such, we composed this phase II study of P + I as second-line therapy for advanced EAC. Methods: The primary endpoint is overall response (OR) as measured by RECIST (imaging every 2 cycles). Secondary endpoints include overall survival, safety/toxicity and correlative studies. Patients with a history of one prior treatment will be treated with P 9 mg/m2 on day 1 and I 125 mg/m2 on days 1 and 8 of each 21 day cycle to a maximum of 6 cycles. Inclusion criteria include confirmed EAC, measurable disease, no prior I or P, PS <2 and normal organ function. Exclusion criteria include use of CYP 3A4 inhibitors, prior anti-EGFR therapy, uncontrolled intercurrent illness. A Simon two-stage design uses power of 80% and a type I error of 0.05. 18 patients will be tested in the first stage, and the trial will be terminated if 2 or fewer respond. In the second stage, a total of 43 patients will be studied. Correlative Studies: Research blood and tissue will be obtained pre-treatment and during the third week of cycle 2. Blood will be studied for the role of FcgR receptors on the effector cell surface leading to antibody-directed cellular cytotoxicity. Tumor tissues will be analyzed for pharmacodynamic (PD) and pharmacogenomic (PG) effects by measurement of EGFR pathway components using FISH and IHC and by kras mutation analysis. Enrollment: The study recently opened at UPMC, and two patients are enrolled. Significance: Along with the primary endpoint of OR, the goal of this trial is to utilize sequential tumor and blood sampling to study PD and PG correlates. The goal is to improve patient selection for targeted therapies in future trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen