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.
- Author:
Ji Youn HAN
1
;
Ki Hyeong LEE
;
Sang We KIM
;
Young Joo MIN
;
Eunkyung CHO
;
Youngjoo LEE
;
Soo Hyun LEE
;
Hyae Young KIM
;
Geon Kook LEE
;
Byung Ho NAM
;
Hyesun HAN
;
Jina JUNG
;
Jin Soo LEE
Author Information
- Publication Type:Original Article
- Keywords: Epidermal growth factor receptor; Poziotinib; Non-small-cell lung carcinoma; T790M; PIK3CA
- MeSH: Adenocarcinoma*; Biopsy; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Epidermal Growth Factor*; Erlotinib Hydrochloride; Exanthema; Humans; Inflammation; Lung; Phosphotransferases*; Plasma; Receptor, Epidermal Growth Factor*; Stomatitis
- From:Cancer Research and Treatment 2017;49(1):10-19
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs. MATERIALS AND METHODS: This single-arm phase II study included EGFR-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; 19 EGFR T790M mutations and two PIK3CA mutations 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 or PIK3CA mutations 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. CONCLUSION: Low activity of poziotinib was detected in patients with EGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation.
