Erlotinib plus Gemcitabine Compared with Gemcitabine Alone in Patients with Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group J Clin Oncol 25: R2 변자민 / Prof 동석호

BACKGROUND Pancreatic cancer Gemcitabine: Standard treatment for advanced pancreatic cancer 4 th Since then, Gemcitabine + α < Gemcitabine alone

BACKGROUND HER1/EGF R overexpressio n 1. Poor prognosis 2. Disease progression 1.Decreased cancer growth & metastasis 2.Improved anticancer effects of gemcitabine AIM: Investigate the effects of adding erlotinib (an oral HER1/EGFR tyrosine kinase inhibitor) to gemcitabine in patients with unresectable, locally advanced or metastatic pancreatic cancer

METHODS -STUDY DESIGN & TREATMENT Conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG): A double-blind, placebo controlled, international, phase III trial October 2011 ~ January 2003 (569 patients) Patients randomly assigned to receive gemcitabine plus either erlotinib or a matched placebo GemcitabineCycle 1 (8 weeks): 1g/m 2 on days 1, 8, 15, 22, 29, 36, 43 -> 1 week rest Cycle 2~ (4 weeks): 1g/m 2 on days 1, 8, 15 -> 1 week rest Erlotinib100 or 150mg/day until disease progression or unmanageable toxicity

METHODS -ELIGIBILITY CRITERIA Primary end points: overall survival Secondary end points: progression free survival, response rate, response duration, toxicity, quality of life, correlation of baseline tissue HER1/EGFR level Eligibility criteria: –Histologic or cytologic evidence of locally advanced or metastatic adenocarcinoma of the pancreas with measurable or assessable disease –ECOG performance status of 0,1,2 –Adequate hematologic, renal, hepatic function  Prior chemotherapy not permitted

METHODS - ASSESSMENTS & STATISTICAL ANALYSIS Assessments –Response and progression evaluated using Response Evaluation Criteria in Solid Tumors q 8 weeks –Toxicity assessed using the National Cancer Institute Common Toxicity Criteria at every visit –QOL measured using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire q 4 weeks –HER1/EGFR analysis conducted by immunohistochemistry using DAKO EGFR Pharm Dx kits ( positive test: ≥10% of tumor cells demonstrating membranous staining) Statistical analysis

RESULTS -BASELINE CHARACTERISTICS Oct 2001 ~ Jan 2003, 176 centers, 17 countries

RESULTS -SURVIVAL CURVES P=0.02 3

RESULTS -HAZARD RATIO OF SURVIVAL

RESULTS - ADVERSE EVENTS

RESULTS - OVERALL SURVIVAL BY RASH GRADE The presence of rash ∝ likelihood of achieving disease control (P=0.05) The median survival rates for patients with grade 0,1,and 2+ rash were 5.3, 5.8, 10.5 months; the 1-year survival rates 16%, 9%, 43% (P < 0.001)

CONCLUSIONS  The first randomized phase III trial to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine  Recommended dose of erlotinib with gemcitabine is 100mg/day