Neratinib, an Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor:Results of a Phase II Trial in Patients With Advanced Non-Small-Cell Lung Cancer
作者： Lecia V. Sequist , Benjamin Besse , Thomas J. Lynch , Vincent A. Miller , Kwok K. Wong
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摘要: Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have had a significant impact on non–small-cell lung cancer (NSCLC) outcomes, particularly for patients with EGFR mutations. Resistance emerges after 9 to 12 months, primarily mediated by the T790M resistance mutation. We studied neratinib, an irreversible pan-ErbB TKI that may overcome T790M. Patients and Methods advanced NSCLC underwent sequencing of available tumor tissue at enrollment. Those ≥ weeks prior therapy were placed in arm A if they mutation positive or B wild-type. Arm C included TKI-naive adenocarcinoma light smoking histories (≤ 20 pack-years). All received daily oral initially 320 mg but subsequently reduced 240 because excessive diarrhea. The primary end point was objective response rate (RR). Results One-hundred sixty-seven treated: 91 A, 48 B, 28 C. Diarrhea...
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