1.A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation
Brian Thiessen • Clinton Stewart • Ming Tsao • Suzanne Kamel-Reid. Cancer Chemother Pharmacol (2010) 65:353–361
We were unable to demonstrate any beneWt of lapatinib in the 17 patients enrolled in the phase II arm of this trial. Only four patients demonstrated stable disease and 13 patients showed early progression, thus, even in the absence of response, there was no signal of activity in terms of delay in progression in meaningful numbers of patients. Because of these results, as per protocol, the phase II portion of the trial was closed to accrual. At that time, seven patients had been enrolled into the phase I arm of the trial and although a recommended dose had not been identiWed, the lack of eYcacy of the agent made the pursuit of a recommended dose in this population no longer relevant. In both EIAED and non-EIAED patients, we were able to con- Wrm that lapatinib was a well tolerated agent. No Grade 4 toxicities were seen and no cardiac toxicity was identiWed. There are several possible reasons for the lack of eYcacy in this tumor group. Lapatinib may perform better in cells that have both ErB-1 and ErbB-2 expression rather than isolated ErbB-1 overexpression. In fact, lapatinib may bind only to inactive/intermediate form of EGFR and constitutively active EGFR (i.e., EGFRvIII mutation) may not be inhibited at all.
2.Cost-effectiveness of lapatinib plus capecitabine in women with HER2+ metastatic breast cancer who have received prior therapy with trastuzumab
Thomas E. Delea • Paul Tappenden • Oleg Sofrygin • Dominy Browning. Eur J Health Econ (2012) 13:589–603
EGF100151 was a phase III randomized controlled trial to evaluate the efﬁcacy and safety of combined therapy with lapatinib, an orally administered dual inhibitor of ErbB1 and HER2, plus capecitabine versus capecitabine monotherapy in women with HER2-positive metastatic breast cancer previously treated with an anthracycline and a taxane (for adjuvant and/or metastatic disease) and trastuzumab (for metastatic disease) . Patients in the combination therapy arm received lapatinib 1,250 mg daily continuously plus capecitabine 2,000 mg/m2 daily for 14 days every 3 weeks. Those in the capecitabine monotherapy arm received capecitabine 2,500 mg/m2 daily for 14 days every 3 weeks. Approximately one-half of subjects had received C4 prior lines of chemotherapy prior to randomization. Based on the recommendation of an independent data-monitoring committee reviewing data up to 15 November 2005, enrolment into the trial was discontinued and crossover to lapatinib plus capecitabine was offered to women receiving capecitabine monotherapy as of 3 April 2006.
3.Pooled analysis of diarrhea events in patients with cancer treated with lapatinib
John P. Crown, Harold A. Burris III, Fran Boyle , Suzanne Jones, Maria Koehler. Breast Cancer Res Treat (2008) 112:317–325
Lapatinib (Tykerb®/Tyverb®; GlaxoSmithKline, Philadelphia, PA) is an oral, dual tyrosine kinase inhibitor targeting both EGFR (ErbB1) and HER2 (ErbB2) receptors. Lapatinib is approved in the United States, Switzerland, Australia, and several other international markets for the treatment of advanced or metastatic breast cancer in patients with HER2-positive tumors who have progressed on treatment regimens containing an anthracycline, a taxane, and trastuzumab. Lapatinib is clinically active as a single agent or in combination with various chemotherapy agents in patients with HER2-positive breast cancer and other solid tumors.
4.Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases
Nancy U. Lin • Wolfgang Eierman • Richard Greil • Mario Campone. J Neurooncol (2011) 105:613–620
Lapatinib is an orally bioavailable, 4-aniloquinazoline tyrosine kinase inhibitor of the epidermal growth factor and HER2. In animal models, lapatinib inhibits CNS outgrowth of HER2-positive cell lines. CNS therapeutic levels have been demonstrated in tumor resection specimens in patients with glioblastoma multiforme. Two phase 2 trials have evaluated lapatinib monotherapy in patients with progressive HER2-positive, brain metastases.