View Full Version : results of trial of Lapatinib for IBC --Lani (having trouble logging in)

04-28-2009, 06:54 AM

04-28-2009, 09:38 AM
Direct anti-tumor and anti-vascular effects were studied of Tykerb in fresh biopsy specimens of breast cancer and presented at the American Society of Clinical Oncology Breast Cancer Symposium on September 5, 2008.

While the other clinically-available 'nib' drugs have been shown to have anti-vascular activity, anti-vascular activity of Tykerb has not been previously reported.

Angiogenesis studies are limited by the clinical relevance of laboratory model systems. They don't do "real world" studies under "real world" conditions. Patient outcomes need to be reported in real-time, so patients and cancer physicians can learn immediately if and how patients are benefiting from new drug therapies.

Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood can identify the activity of both single drugs and combinations of drugs at the level of individual patients with individual cancers. It works by measuring drug effects (real-time) upon endothelial cells which make up blood vessels.

Conclusions of the study had shown that Tykerb has antivascular activity superior to that of Nexavar. Avastin + Tykerb may be the first clinically-exploitable antivascular drug combination. High dose, intermittent 'bolus' schedules of Tykerb to coincide with Avastin administration may be clinically advantageous, even in HER2-negative tumors.

The system utilized for the study was a functional profiling assay, which may be used to individualize antivascular therapy. It can be adapted for simple, inexpensive and sensitive/specific detection of tissue and circulating microvascular cells in a variety of neoplastic and non-neoplastic conditions, for drug development, and individualized cancer treatment.

It can accurately sort drugs into categories of above average probability of providing clinical benefit on one hand and below average probability of providing clinical benefit on the other hand, based both on tumor response and patient survival.

04-28-2009, 08:39 PM
<dl class="AbstractPlusReport"><dt class="head">1: Lancet Oncol. (javascript:AL_get(this,%20'jour',%20'Lancet%20Onc ol.');) 2009 Apr 24. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-14702045-ONC.gif (http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=19394894&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S1470-2045%2809%2970087-7) <script language="JavaScript1.2"><!-- var Menu19394894 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=19394894&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""] ] --></script>Links (javascript:PopUpMenu2_Set(Menu19394894);)
</dt><dd class="abstract"> Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study.

<!--AuthorList-->Kaufman B (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Kaufman%20B%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Trudeau M (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Trudeau%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Awada A (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Awada%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Blackwell K (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Blackwell%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Bachelot T (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Bachelot%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Salazar V (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Salazar%20V%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Desilvio M (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Desilvio%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Westlund R (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Westlund%20R%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Zaks T (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Zaks%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Spector N (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Spector%20N%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Johnston S (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Johnston%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
The Chaim Sheba Medical Center, Tel Hashomer, Israel.
BACKGROUND: Inflammatory breast cancer is an aggressive and biologically distinct form with a higher frequency of HER2 overexpression than other breast cancers. For patients with resistance to conventional anthracycline or taxane and trastuzumab treatment, options are limited. Lapatinib, an oral reversible inhibitor of epidermal growth factor receptor tyrosine kinases, previously had a 50% response rate in a cohort of 30 patients with HER2-overexpressing (HER2+) recurrent or anthracycline-refractory inflammatory breast cancer. We aimed to assess efficacy of lapatinib in an expanded cohort of patients with relapsed or refractory HER2+ disease. METHODS: From March, 2005, to September, 2007, 126 patients with relapsed or refractory HER2+ inflammatory breast cancer were treated with lapatinib 1500 mg once daily in a non-randomised, open-label, phase II study. Pretreatment tumour biopsies were done to verify pathological features of inflammatory breast cancer. Skin disease was assessed every 4 weeks, and response in sites of measurable locally advanced or metastatic disease were assessed by response evaluation in solid tumours (RECIST) criteria every 8 weeks. The primary aim was to assess combined objective response rate, by clinically evaluable skin disease criteria and RECIST, if applicable. Analyses were done by intention to treat; patients with missing data were treated as non-responders. This study is registered with ClinicalTrials.gov, number NCT00105950. FINDINGS: Clinical presentation and biomarker analysis showed a tumour molecular profile consistent with inflammatory breast cancer. No patients had complete response. 49 patients (39%; 95% CI 30-48) had partial response. Median progression-free survival was 14.6 weeks (95% CI 12.1-16.0), with median duration of response of 20.9 weeks (12.7-32.1). Likelihood of response to lapatinib was not affected by previous treatment with trastuzumab. 130 (92%) of 141 patients had at least one adverse event; 45 (32%) had serious adverse events, the most common were dyspnoea (eight patients) and pleural effusion (six). Five patients had fatal adverse events that were possibly treatment related. INTERPRETATION: Lapatinib monotherapy is a potentially effective treatment for relapsed or refractory HER2+ inflammatory breast cancer. FUNDING: GlaxoSmithKline.