{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:16:53Z","timestamp":1791170213227,"version":"4.1.0"},"reference-count":34,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"25","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2010,9,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Preclinical data have demonstrated that BIBW 2992 is a potent irreversible inhibitor of ErbB1 (EGFR\/HER1) and mutated ErbB1 receptors including the T790M variant, as well as ErbB2 (HER2). A phase I study of continuous once-daily oral BIBW 2992 was conducted to determine safety, maximum-tolerated dose, pharmacokinetics (PK), food effect, and preliminary antitumor efficacy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Patients with advanced solid tumors were treated. PK evaluation was performed after the first dose and at steady-state. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Fifty-three patients received BIBW 2992 at 10 to 50 mg\/d. BIBW 2992 was generally well-tolerated. The most common adverse effects included diarrhea, nausea, vomiting, rash, and fatigue. Dose-limiting toxicities included grade 3 rash (n = 2) and reversible dyspnea secondary to pneumonitis (n = 1). The recommended phase II dose was 50 mg\/d. PK was dose proportional with a terminal elimination half-life ranging between 21.3 and 27.7 hours on day 1 and between 22.3 and 67.0 hours on day 27; BIBW 2992 exposure decreased after food intake. Three patients with non\u2013small-cell lung carcinoma (NSCLC; two with in-frame exon 19 mutation deletions) experienced confirmed partial responses (PR) sustained for 24, 18, and 34 months, respectively. Two other patients (esophageal carcinoma and NSCLC) had nonconfirmed PRs. A patient with a PR at 10 mg\/d progressed and developed symptomatic brain metastases, which subsequently regressed with an increased dose of 40 mg\/d of BIBW 2992. A further seven patients had disease stabilization lasting \u2265 6 months. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Continuous, daily, oral BIBW 2992 is safe and has durable antitumor activity. It is currently being evaluated in phase III trials. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2009.26.7278","type":"journal-article","created":{"date-parts":[[2010,8,3]],"date-time":"2010-08-03T03:00:31Z","timestamp":1280804431000},"page":"3965-3972","source":"Crossref","is-referenced-by-count":289,"title":["Phase I Trial of the Irreversible EGFR and HER2 Kinase Inhibitor BIBW 2992 in Patients With Advanced Solid Tumors"],"prefix":"10.1200","volume":"28","author":[{"given":"Timothy A.","family":"Yap","sequence":"first","affiliation":[{"name":"From the Drug Development Unit, the Royal Marsden National Health Service Foundation Trust, and The Institute of Cancer Research, Sutton, Surrey; Northern Institute for Cancer Research, Newcastle upon Tyne; Boehringer Ingelheim, Bracknell; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; and Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Vidal","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, the Royal Marsden National Health Service Foundation Trust, and The Institute of Cancer Research, Sutton, Surrey; Northern Institute for Cancer Research, Newcastle upon Tyne; Boehringer Ingelheim, Bracknell; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; and Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Adam","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, the Royal Marsden National Health Service Foundation Trust, and The Institute of Cancer Research, Sutton, Surrey; Northern Institute for Cancer Research, Newcastle upon Tyne; Boehringer Ingelheim, Bracknell; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; and Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Stephens","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, the Royal Marsden National Health Service Foundation Trust, and The Institute of Cancer Research, Sutton, Surrey; 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