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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 10 - 19 (10page)
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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 PIK3CAmutations 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.
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참고문헌 (20)
참고문헌 신청
Cha MY / 2012 / Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models / Int J Cancer 130 :
Ellis PM / 2014 / Dacomitinib compared with placebo in pretreated patients with advanced or metastatic non-small-cell lung cancer (NCIC CTG BR.26): a double-blind, randomise
Gridelli C / 2012 / First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer : the TORCH randomized trial / J C
Jackman D / 2010 / Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in nonsmall-cell lung cancer / J Clin Oncol 28 :
Janne PA / 2015 / AZD9291 in EGFR inhibitor-resistant nonsmall-cell lung cancer / N Engl J Med 372 : 1689 ~ 1699
Ellis PM / 2014 / Dacomitinib compared with placebo in pretreated patients with advanced or metastatic non-small-cell lung cancer (NCIC CTG BR.26): a double-blind, randomise
Gridelli C / 2012 / First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer : the TORCH randomized trial / J C
Jackman D / 2010 / Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in nonsmall-cell lung cancer / J Clin Oncol 28 :
Janne PA / 2015 / AZD9291 in EGFR inhibitor-resistant nonsmall-cell lung cancer / N Engl J Med 372 : 1689 ~ 1699
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