title: A Randomized Phase 2 Study Comparing the Combination of Ficlatuzumab and Gefitinib with Gefitinib Alone in Asian Patients with Advanced Stage Pulmonary Adenocarcinoma.
abstract: A randomized phase 2 study was designed to compare the combination of ficlatuzumab (AV-299), a humanized hepatocyte growth factor-neutralizing monoclonal antibody, plus gefitinib versus gefitinib monotherapy in a pulmonary adenocarcinoma population clinically enriched for EFGR tyrosine kinase inhibitor-sensitizing mutations.
  
  
  
  A total of 188 patients were randomized 1:1 to receive either gefitinib or ficlatuzumab plus gefitinib treatment. Patients who demonstrated disease control in the single-agent gefitinib arm were allowed to cross over to ficlatuzumab plus gefitinib treatment upon disease progression. Molecular analyses included tumor EGFR mutation status and retrospective proteomic testing using VeriStrat, a multivariate test based on mass spectrometry.
  
  
  
  The addition of ficlatuzumab to gefitinib did not provide significant improvement over gefitinib monotherapy for the primary end point of overall response rate or the secondary end points of progression-free survival and overall survival. In the subgroup classified as VeriStrat poor, the addition of ficlatuzumab to gefitinib showed significant improvement in both progression-free survival and overall survival in both the intent-to-treat population and the subgroup with EGFR tyrosine kinase inhibitor-sensitizing mutations. For all patients, the most frequent adverse events were diarrhea, dermatitis acneiform, and paronychia.
  
  
  
  Although the trial showed no significant benefit from the addition of ficlatuzumab to gefitinib in the overall population of Asian patients with advanced-stage pulmonary adenocarcinoma, the biomarker data suggest that patients classified as VeriStrat poor may benefit from ficlatuzumab combination therapy.
authors.affiliation: State Key Laboratory of South China, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, Republic of China. Electronic address: tony@clo.cuhk.edu.hk.
authors.forename: Tony Shu Kam
authors.initials: TS
authors.lastname: Mok
authors.affiliation: Prince of Songkla University, Songkhla, Thailand.
authors.forename: Sarayut Lucien
authors.initials: SL
authors.lastname: Geater
authors.affiliation: National Cheng Kung University Hospital, Tainan City, Republic of China.
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
authors.affiliation: National Cancer Centre, Singapore.
authors.forename: Eng-Huat
authors.initials: EH
authors.lastname: Tan
authors.affiliation: National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Republic of China.
authors.forename: James Chi-Hsin
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Republic of China.
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.affiliation: AVEO Oncology, Cambridge, Massachusetts.
authors.forename: May
authors.initials: M
authors.lastname: Han
authors.affiliation: AVEO Oncology, Cambridge, Massachusetts.
authors.forename: Philip
authors.initials: P
authors.lastname: Komarnitsky
authors.affiliation: AVEO Oncology, Cambridge, Massachusetts.
authors.forename: Francis
authors.initials: F
authors.lastname: Payumo
authors.affiliation: Biodesix, Inc., Boulder, Colorado.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Garrus
authors.affiliation: Biodesix, Inc., Boulder, Colorado.
authors.forename: Sandra
authors.initials: S
authors.lastname: Close
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People; D018572:Disease-Free Survival; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D011799:Quinazolines; C583360:ficlatuzumab; D000077156:Gefitinib
keywords: EGFR TKI; Ficlatuzumab; HGF; Lung cancer; VeriStrat