[en] BACKGROUND: The Lapatinib Expanded Access Program (LEAP) was designed to provide access to lapatinib plus capecitabine for HER2-positive metastatic breast cancer patients who previously received an anthracycline, a taxane, and a trastuzumab and had no other treatment options. PATIENTS AND METHODS: LEAP opened globally and enrollment continued until lapatinib received regulatory approval in each participating country. Patients were assessed for progression-free survival (PFS) and overall survival (OS) and monitored for serious adverse events (SAEs). RESULTS: As of 30 September 2008, 4283 patients from 45 countries enrolled in LEAP. The median treatment duration was 24.7 weeks. The most common drug-related SAEs were diarrhea (9.7%), vomiting (4.3%), and nausea (2.4%) and were mainly grade 3 or higher. The incidences of special interest SAEs were decreased left ventricle ejection fraction (0.5%), interstitial lung disease/pneumonitis (0.2%), and serious hepatobiliary events (0.4%). This safety profile is consistent with the overall lapatinib program. The median PFS and OS were 21.1 [95% confidence interval (CI) = 20.1-22.3] and 39.6 (95% CI = 37.7-40.7) weeks, respectively (n = 4006). Subgroup analysis showed longer PFS and OS in patients who had not received prior capecitabine. CONCLUSIONS: These results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial.
Disciplines :
Oncology
Author, co-author :
Capri, G.
Chang, J.
Chen, S. C.
Conte, P.
Cwiertka, K.
Jerusalem, Guy ; Centre Hospitalier Universitaire de Liège - CHU > Oncologie médicale
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Bibliography
American Cancer Society. Global Cancer Facts and Figures 2007 [on-line]; http://www.cancer.org/docroot/STT/content/STT_1x_Global_Cancer_Facts_and_Figures_2007.asp (10 March, 2009, date last accessed).
Johnston S, Pegram M, Press M et al. Lapatinib combined with letrozole vs. letrozole alone for front line postmenopausal hormone receptor positive (HR+) metastatic breast cancer (MBC): first results from the EGF30008 Trial. Abstract presented at 31st Annual San Antonio Breast Cancer Symposium; December 10-14, 2008; San Antonio, TX.
Zahnow CA. ErbB receptors and their ligands in the breast. Expert Rev Mol Med 2006; 8: 1-21.
Zhang H, Berezov A, Wang Q et al. ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest 2007; 117: 2051-2058.
Badache A, Goncalves A. The ErbB2 signaling network as a target for breast cancer therapy. J Mammary Gland Biol Neoplasia 2006; 11: 13-25.
Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707-712.
Rusnak DW, Lackey K, Affleck K et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther 2001; 1: 85-94.
Geyer CE, Forster J, Lindquist D et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355: 2733-2743.
Cameron D, Casey M, Press M et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 2008; 112: 533-543.
Di Leo A, Gomez HL, Aziz Z et al. Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol 2008; 26: 5544-5552.
Gomez HL, Doval DC, Chavez MA et al. Efficacy and safety of lapatinib as firstline therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol 2008; 26: 2999-3005.
Boccardo F, Kaufman B, Baselga J et al. Evaluation of lapatinib plus capecitabine in patients with brain metastases from HER2+ breast cancer enrolled in the Lapatinib Expanded Access Program (LEAP) and French Authorisation Temporaire d'Utilisation (ATU) Poster presented at 44th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2008; Chicago, IL.
Campone M, El-Kouri C, Cottu P et al. French Lapatinib Authorization for Temporary Use (ATU): design, operation and initial safety data. Poster presented at 6th European Breast Cancer Conference; April 15-19, 2008; Berlin, Germany.
De Placido S, Capri G, Ro J et al. Lapatinib Expanded Access Program (LEAP): updated safety data Poster presented at European Society for Medical Oncology 33rd Annual Meeting; September 12-16, 2008; Stockholm, Sweden.
Capdeville R, Krahnke T, Hatfield A et al. Report of an international expanded access program of imatinib in adults with Philadelphia chromosome positive leukemias. Ann Oncol 2008; 19: 1320-1326.
Venturini M, Paridaens R, Rossner D et al. An open-label, multicenter study of outpatient capecitabine monotherapy in 631 patients with pretreated advanced breast cancer. Oncology 2007; 72: 51-57.
Lin NU, Diéras V, Paul D et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res 2009; 15: 1452-1459.
Suter TM, Cook-Bruns N, Barton C. Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer. Breast 2004; 13: 173-183.
Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783-792.
Perez EA, Koehler M, Byrne J et al. Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin Proc 2008; 83: 679-686.
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