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BURSTEIN H ET AL: "HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: preliminary phase 2 results in patients with advanced breast cancer.", December 2007 (2007-12), BREAST CANCER RESEARCH AND TREATMENT, VOL. 106, NR. SUPPL. 1, PAGE(S) S268, 30TH ANNUAL SAN ANTONIO BREAST CANCER SYMPOSIUM; SAN ANTONIO, TX, USA; DECEMBER 13 -16, 2007, XP002591682, ISSN: 0167-6806 * See abstract: clinical phase II study involving administration of neratinib (HKI-272), to patients affected by advanced breast cancer previousl administered trastuzumab * (B1)

HUDIS CLIFFORD A ET AL: "Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system.", JOURNAL OF CLINICAL ONCOLOGY : OFFICIAL JOURNAL OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY 20 MAY 2007, vol. 25, no. 15, 20 May 2007 (2007-05-20), pages 2127-2132, XP002754386, ISSN: 1527-7755 (B1)

ILIADIS A ET AL: "APIS: a software for model identification, simulation and dosage regimen calculations in clinical and experimental pharmacokinetics", COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE, ELSEVIER, AMSTERDAM, NL LNKD- DOI:10.1016/0169-2607(92)90103-E, vol. 38, no. 4, 1 August 1992 (1992-08-01) , pages 227-239, XP024237123, ISSN: 0169-2607 [retrieved on 1992-08-01] (B1)

WONG KWOK-K ET AL: "A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.", 1 April 2009 (2009-04-01), CLINICAL CANCER RESEARCH : AN OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH 1 APR 2009 LNKD- PUBMED:19318484, VOL. 15, NR. 7, PAGE(S) 2552 - 2558, XP002591681, ISSN: 1078-0432 * See abstract, page 2553, first column and passage bridging pages 2556 and 2557: phase II trials indicates that neratinib has antitumoral activity in patients affected by breast cancer positive to HER-2/neu (ErbB-2), previously treated with trastuzumab * (B1)

WIDAKOWICH C ET AL: "HER-2 positive breast cancer: What else beyond trastuzumab-based therapy?", ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, BENTHAM SCIENCE PUBLISHERS LTD, NL LNKD- DOI:10.2174/187152008784533062, vol. 8, no. 5, 1 June 2008 (2008-06-01), pages 488-496, XP008114462, ISSN: 1871-5206 (B1)

WISSNER ALLAN ET AL: "The development of HKI-272 and related compounds for the treatment of cancer.", August 2008 (2008-08), ARCHIV DER PHARMAZIE AUG 2008 LNKD- PUBMED:18493974, VOL. 341, NR. 8, PAGE(S) 465 - 477, XP002591683, ISSN: 0365-6233 * See abstract and see page 475, passage bridging columns 1-2: HKI-272 is an irreversible HER-2 inhibitor which maintains activity against cancers resistant to reversible inhibitors (gefitinib and erlotinib) * * See page 476, passage bridging columns 1-2: HKI-272 produces 51% response in patients affected by breast cancer after trastumab therapy * (B1)

WO-A1-2007/056118 (B1)

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