PMID- 18421051 OWN - NLM STAT- MEDLINE DCOM- 20080429 LR - 20240323 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 26 IP - 12 DP - 2008 Apr 20 TI - Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. PG - 1993-9 LID - 10.1200/JCO.2007.12.3588 [doi] AB - PURPOSE: One third of women with advanced human epidermal growth factor receptor 2 (HER-2)-positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2-positive brain metastases. PATIENTS AND METHODS: Patients had HER-2-positive breast cancer, progressive brain metastases, prior trastuzumab treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included objective response in non-CNS sites, time to progression, overall survival, and toxicity. RESULTS: Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%). CONCLUSION: The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2-positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point. FAU - Lin, Nancy U AU - Lin NU AD - Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. FAU - Carey, Lisa A AU - Carey LA FAU - Liu, Minetta C AU - Liu MC FAU - Younger, Jerry AU - Younger J FAU - Come, Steven E AU - Come SE FAU - Ewend, Matthew AU - Ewend M FAU - Harris, Gordon J AU - Harris GJ FAU - Bullitt, Elizabeth AU - Bullitt E FAU - Van den Abbeele, Annick D AU - Van den Abbeele AD FAU - Henson, John W AU - Henson JW FAU - Li, Xiaochun AU - Li X FAU - Gelman, Rebecca AU - Gelman R FAU - Burstein, Harold J AU - Burstein HJ FAU - Kasparian, Elizabeth AU - Kasparian E FAU - Kirsch, David G AU - Kirsch DG FAU - Crawford, Ann AU - Crawford A FAU - Hochberg, Fred AU - Hochberg F FAU - Winer, Eric P AU - Winer EP LA - eng GR - M01 RR000046/RR/NCRR NIH HHS/United States GR - P50 CA058223/CA/NCI NIH HHS/United States GR - R01 EB000219/EB/NIBIB NIH HHS/United States GR - M01RR00046/RR/NCRR NIH HHS/United States GR - CA58223/CA/NCI NIH HHS/United States GR - CA89393/CA/NCI NIH HHS/United States GR - R01EB000219/EB/NIBIB NIH HHS/United States GR - P50 CA089393/CA/NCI NIH HHS/United States GR - R01 EB000219-09/EB/NIBIB NIH HHS/United States GR - P30 CA006516/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - 0VUA21238F (Lapatinib) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM CIN - J Clin Oncol. 2008 Nov 1;26(31):5137-8; author reply 5138-9. PMID: 18838700 MH - Adult MH - Aged MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Brain Neoplasms/*drug therapy/enzymology/*secondary MH - Breast Neoplasms/*drug therapy/enzymology/*pathology MH - Female MH - Humans MH - Lapatinib MH - Middle Aged MH - Prospective Studies MH - Protein Kinase Inhibitors/adverse effects/therapeutic use MH - Quinazolines/adverse effects/*therapeutic use MH - Receptor, ErbB-2/*biosynthesis MH - Treatment Outcome PMC - PMC4524351 MID - NIHMS511902 COIS- Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Nancy U. Lin, GlaxoSmithKline (C); Lisa A. Carey, Genentech (U), GlaxoSmithKline (U), Pfizer (U), Bristol Meyers Squib (U); John W. Henson, GlaxoSmithKline (C); Elizabeth Kasparian, GlaxoSmithKline (C); Eric P. Winer, Genentech (C), GlaxoSmithKline (C) Stock Ownership: None Honoraria: Minetta C. Liu, GlaxoSmithKline; Elizabeth Kasparian, GlaxoSmithKline Research Funding: Nancy U. Lin, GlaxoSmithKline; Lisa A. Carey, Genentech, GlaxoSmithKline, Bristol Meyers Squib; Minetta C. Liu, GlaxoSmithKline; Eric P. Winer, Genentech, GlaxoSmithKline Expert Testimony: None Other Remuneration: None EDAT- 2008/04/19 09:00 MHDA- 2008/04/30 09:00 PMCR- 2015/08/04 CRDT- 2008/04/19 09:00 PHST- 2008/04/19 09:00 [pubmed] PHST- 2008/04/30 09:00 [medline] PHST- 2008/04/19 09:00 [entrez] PHST- 2015/08/04 00:00 [pmc-release] AID - 26/12/1993 [pii] AID - 10.1200/JCO.2007.12.3588 [doi] PST - ppublish SO - J Clin Oncol. 2008 Apr 20;26(12):1993-9. doi: 10.1200/JCO.2007.12.3588.