Mok T.S.KGeater S.LSu W.-CTan E.-HCHIH-HSIN YANGChang G.-CHan MKomarnitsky PPayumo FGarrus J.EClose SPark K.2020-05-262020-05-2620161556-0864https://www.scopus.com/inward/record.uri?eid=2-s2.0-84991098179&doi=10.1016%2fj.jtho.2016.05.038&partnerID=40&md5=12703cd2ce3e8459fdbdffd39ff5762dhttps://scholars.lib.ntu.edu.tw/handle/123456789/494997Introduction: 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.EGFR TKI; Ficlatuzumab; HGF; Lung cancer; VeriStrat[SDGs]SDG1[SDGs]SDG3alanine 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; Quinazolinesjournal article10.1016/j.jtho.2016.05.038274487612-s2.0-84991098179