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Mefatinib is a novel, bioavailable, second-generation, irreversible pan-\n                    <jats:italic>EGFR<\/jats:italic>\n                    inhibitor. This phase Ib\/II open-label, single-arm, multi-center study investigated the efficacy, safety, biomarker, and resistance mechanisms of mefatinib in the first-line treatment of patients with advanced\n                    <jats:italic>EGFR<\/jats:italic>\n                    -mutant NSCLC. This study included 106 patients with\n                    <jats:italic>EGFR<\/jats:italic>\n                    -mutant stage IIIB-IV NSCLC who received first-line mefatinib at a daily dose of either 60\u2009mg (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200951) or 80\u2009mg (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200955). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The cohort achieved an ORR of 84.9% and DCR of 97.2%. The median PFS was 15.4 months and the median OS was 31.6 months. Brain metastasis was detected in 29% of patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200931) at diagnosis and demonstrated an ORR of 87.1%, PFS of 12.8 months, and OS of 25.2 months. Adverse events primarily involved skin and gastrointestinal toxicities, which were well-tolerated and manageable. Analyses of mutation profiles were performed using targeted sequencing of plasma samples at baseline, first follow-up 6 weeks from starting mefatinib therapy (F1), and at progression. Patients with concurrent\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations had comparable PFS as wild-type\n                    <jats:italic>TP53<\/jats:italic>\n                    (14.0 vs 15.4 months;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.315). Furthermore, circulating tumor DNA clearance was associated with longer PFS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.040) and OS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002).\n                    <jats:italic>EGFR<\/jats:italic>\n                    T790M was the predominant molecular mechanism of mefatinib resistance (42.1%, 16\/38). First-line mefatinib provides durable PFS and an acceptable toxicity profile in patients with advanced\n                    <jats:italic>EGFR<\/jats:italic>\n                    -mutant NSCLC.\n                  <\/jats:p>","DOI":"10.1038\/s41392-021-00773-3","type":"journal-article","created":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T21:03:04Z","timestamp":1635714184000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mefatinib as first-line treatment of patients with advanced EGFR-mutant non-small-cell lung cancer: a phase Ib\/II efficacy and biomarker study"],"prefix":"10.1038","volume":"6","author":[{"given":"Pingli","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqing","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingge","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liren","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianya","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youfei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"773_CR1","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1056\/NEJMoa040938","volume":"350","author":"TJ Lynch","year":"2004","unstructured":"Lynch, T. 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