title: Phase 2 trial of erlotinib with or without PF-3512676 (CPG 7909, a Toll-like receptor 9 agonist) in patients with advanced recurrent EGFR-positive non-small cell lung cancer.
abstract: This phase 2 study assessed PF-3512676 plus erlotinib in patients with epidermal growth factor receptor-positive advanced non-small cell lung cancer after prior chemotherapy failure. Patients were randomized 1:1 to PF-3512676 (0.20 mg/kg injected subcutaneously once weekly) plus erlotinib (150 mg daily) or erlotinib alone. The primary objective was to estimate progression-free survival (PFS). Patients received PF-3512676 plus erlotinib (n = 18) or erlotinib alone (n = 21). The study was halted because an unplanned interim analysis indicated that large improvement in PFS with addition of PF-3512676 would be unlikely. In the PF-3512676-plus-erlotinib and erlotinib-alone arms, median PFS was 1.6 and 1.7 mo (hazard ratio, 1.00; 95% confidence interval, 0.5-2.0; P = 0.9335), respectively. Salient grade ≥ 3 adverse events in PF-3512676-plus-erlotinib and erlotinib-alone arms were diarrhea (5/0), dyspnea (5/6), fatigue (4/1), other flu-like symptoms (2/0), anemia (2/1), and lymphocytopenia (based on laboratory values, 1/4). Adding PF-3512676 to erlotinib did not show potential for increased progression-free survival over erlotinib alone in patients with advanced recurrent epidermal growth factor receptor-positive non-small cell lung cancer.
authors.affiliation: Penn State Hershey Cancer Institute, Milton S. Hershey Medical Center, Hershey, PA, USA. cbelani@psu.edu
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: John J
authors.initials: JJ
authors.lastname: Nemunaitis
authors.forename: Abraham
authors.initials: A
authors.lastname: Chachoua
authors.forename: Peter D
authors.initials: PD
authors.lastname: Eisenberg
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Raez
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Cuevas
authors.forename: Cecile B
authors.initials: CB
authors.lastname: Mather
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Benner
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Meech
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051217:Toll-Like Receptor 9 / Q000819:agonists*
chemical_list: D009838:Oligodeoxyribonucleotides; C483020:ProMune; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: EGFR; PF-3512676; Toll-like receptor 9; carcinoma; epidermal growth factor; erlotinib; non-small cell lung cancer; receptor