title: Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer.
abstract: This trial was designed to assess efficacy and safety of erlotinib with sorafenib in the treatment of patients with advanced pancreatic adenocarcinoma. An exploratory correlative study analyzing pretreatment serum samples using a multivariate protein mass spectrometry-based test (VeriStrat®), previously shown to correlate with outcomes in lung cancer patients treated with erlotinib, was performed. Patients received sorafenib 400 mg daily along with erlotinib 150 mg daily with a primary endpoint of 8-week progression free survival (PFS) rate. Pretreatment serum sample analysis by VeriStrat was done blinded to clinical and outcome data; the endpoints were PFS and overall survival (OS). Difference between groups (by VeriStrat classification) was assessed using log-rank P values; hazard ratios (HR) were obtained from Cox proportional hazards model. Thirty-six patients received study drug and were included in the survival analysis. Eight-week PFS rate of 46% (95% confidence interval (CI): 0.32-0.67) did not meet the primary endpoint of a rate ≥70%. Thirty-two patients were included in the correlative analysis, and VeriStrat "Good" patients had superior PFS (HR = 0.18, 95% CI: 0.06-0.57; P = 0.001) and OS (HR = 0.31 95% CI: 0.13-0.77, P = 0.008) compared to VeriStrat "Poor" patients. Grade 3 toxicities of this regimen included fever, anemia, diarrhea, dehydration, rash, and altered liver function. This study did not meet the primary endpoint, and this combination will not be further pursued. In this small retrospective analysis, the proteomic classification was significantly associated with clinical outcomes and is being further evaluated in ongoing studies.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Dana B
authors.initials: DB
authors.lastname: Cardin
authors.forename: Laura
authors.initials: L
authors.lastname: Goff
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Charles
authors.initials: C
authors.lastname: Winkler
authors.forename: Russell
authors.initials: R
authors.lastname: DeVore
authors.forename: Larry
authors.initials: L
authors.lastname: Schlabach
authors.forename: Melanie
authors.initials: M
authors.lastname: Holloway
authors.forename: Pam
authors.initials: P
authors.lastname: McClanahan
authors.forename: Krista
authors.initials: K
authors.lastname: Meyer
authors.forename: Julia
authors.initials: J
authors.lastname: Grigorieva
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.forename: Emily
authors.initials: E
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D000077157:Sorafenib
chemical_list: D010671:Phenylurea Compounds; D011799:Quinazolines; D009536:Niacinamide; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Erlotinib; pancreatic cancer; sorafenib; targeted therapy