title: A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR-Tyrosine Kinase Inhibitors.
abstract: OBJECTIVE
  We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activatingEGFRmutations, who developed acquired resistance (AR) to EGFR-TKIs.
  
  
  METHODS
  This single-arm phase II study includedEGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms.
  
  
  RESULTS
  Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19EGFRT790M mutations and twoPIK3CAmutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M orPIK3CAmutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions.
  
  
  CONCLUSIONS
  Low activity of poziotinib was detected in patients withEGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation.
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea.
authors.forename: Ki Hyeong
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sang-We
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, Ulsan, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Min
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Cho
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Hyae Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Nam
authors.affiliation: Clinical Research Team, Hanmi Pharmaceutical Co., Ltd., Seoul, Korea.
authors.forename: Hyesun
authors.initials: H
authors.lastname: Han
authors.affiliation: Clinical Research Team, Hanmi Pharmaceutical Co., Ltd., Seoul, Korea.
authors.forename: Jina
authors.initials: J
authors.lastname: Jung
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment
chemical_list: D000970:Antineoplastic Agents; C557213:HM781-36B; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Non-small-cell lung carcinoma; PIK3CA; Poziotinib; T790M