期刊
LUNG CANCER
卷 112, 期 -, 页码 195-199出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2017.08.017
关键词
Dacomitinib; Non-small-cell lung cancer; T790M; Egfr; Pulsatile dosing; Tyrosine kinase inhibitors
资金
- Pfizer Inc.
- Astra Zeneca
- Clovis Oncology
- Astellas Pharma
- Pfizer
Background: Dacomitinib is a second-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Pre-clinical data suggest that intermittent pulsatile dosing of dacomitinib may result in inhibition of EGFR T790M. Methods: We evaluated safety, pharmacokinetics and efficacy of intermittent pulsatile dacomitinib in both molecularly unselected patients and patients with lung cancers harboring EGFR T790M (Clinical Trial Registration Number NCT01858389). Results: Thirty-eight patients were treated on study with pulse dacomitinib; sixteen with EGFR T790M in Cohort A and 22 who were not molecularly selected in Cohort B. One patient out of 16 patients in Cohort A had a partial response to study therapy (ORR 6.3%, 95% CI 0.2-30.2%). The median progression-free survival (PFS) in Cohort A was 2.3 months and median PFS in Cohort B was 1.6 months. The adverse event profile was similar to standard daily dose dacomitinib with the most frequent treatment-related toxicities occurring in > 20% of patients being diarrhea, rash, stomatitis, nausea, dry skin, paronychia, fatigue, and decreased appetite. Conclusion: Intermittent pulsatile dacomitinib is safe and relatively well tolerated but is not effective in patients that harbor EGFR T790M or in unselected patients with non-small cell lung cancer.
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