A randomized phase 2 study comparing the combination of ficlatuzumab and gefitinib with gefitinib alone in asian patients with advanced stage pulmonary adenocarcinoma
Journal
Journal of Thoracic Oncology
Journal Volume
11
Journal Issue
10
Pages
1736-1744
Date Issued
2016
Author(s)
Mok T.S.K
Geater S.L
Su W.-C
Tan E.-H
Chang G.-C
Han M
Komarnitsky P
Payumo F
Garrus J.E
Close S
Park K.
Abstract
Introduction: 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. Methods: 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. Results: 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. Conclusions: 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. ? 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Subjects
EGFR TKI; Ficlatuzumab; HGF; Lung cancer; VeriStrat
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; ficlatuzumab; gefitinib; vasculotropin; antineoplastic agent; ficlatuzumab; gefitinib; monoclonal antibody; quinazoline derivative; abnormal laboratory result; acne; adult; advanced cancer; Article; Asian; cancer combination chemotherapy; cancer control; cancer growth; cancer patient; comparative study; controlled study; crossover procedure; dermatitis; diagnostic test; diarrhea; drug dose reduction; drug efficacy; drug safety; drug tolerability; female; fever; folliculitis; human; hypoalbuminemia; lung adenocarcinoma; major clinical study; male; mass spectrometry; monotherapy; multicenter study; overall survival; paronychia; peripheral edema; phase 2 clinical trial; pleura effusion; pneumonia; priority journal; progression free survival; proteomics; randomized controlled trial; respiratory failure; sepsis; side effect; treatment interruption; treatment outcome; treatment response; adenocarcinoma; Asian continental ancestry group; cancer staging; clinical trial; disease free survival; Lung Neoplasms; pathology; Adenocarcinoma; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Asian Continental Ancestry Group; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Neoplasm Staging; Quinazolines
Publisher
Lippincott Williams and Wilkins
Type
journal article