Lapatinib (Tykerb) is an oral drug that has been shown to have activity in HER+ breast cancer in several phase II and III clinical trials. Specifically, Lapatinib is effective in patients with metastatic breast cancer, with inflammatory breast cancer, and possibly, with brain metastases. An ongoing clinical trial and another anticipated clinical trial will investigate Lapatinib as adjuvant treatment in early-stage disease.
Lapatinib is indicated for the treatment of metastatic HER2-positive breast cancer, both in combination with capecitabine in patients who have received taxane, anthracycline and trastuzumab and in combination with letrozole for postmenopausal patients with hormone receptor- and HER2-overexpressing breast cancer.
Not infrequently one encounters HER+ patients who had not been treated with both anthracycline, such as Adriamycin, and taxanes. What about Tykerb for them, alone or in combination? As Adriamycin use declines, this situation has become more and more common.
To understand how off label use can still be reasonable and medically appropriate, one must recall that FDA usually, and certainly in the past, based its approval on randomized prospective studies. Because such studies are expensive and time-consuming, once a drug is approved manufacturers do not often attempt to obtain additional indications. Because studies to the FDA were in patients previously exposed to the anthracyclines and taxanes, the approval was for only such patients; however, Tykerb in other HER+ patients is well supported by a variety of phase II and other studies.
E. Frampton Lapatinib: a review of its use in the treatment of HER2-overexpressing, trastuzumab-refractory, advanced or metastatic breast cancer. Drugs. 2009 Oct 22;69(15):2125-48.
O’Shaughnessy J, Blackwell KL, Burstein H, et al. A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy. Program and abstracts of the 44th American Society of Clinical Oncology Annual Meeting; May 30 – June 3, 2008; Chicago, Illinois. Abstract 1015
W. Janni, J. V. Álvarez, C. A. Papadimitriou, B. Karaszewska, W. Wiest, M. L. Lim, A. Das-Gupta; Heinrich-Heine-Universitaet, Duesseldorf, Germany; Hospital Provincial de Zamora, Zamora, Spain; Hellenic Cooperative Oncology Group Data Office, Athens, Greece; A phase II randomized trial of lapatinib with either vinorelbine or capecitabine in ErbB2-overexpressing first- and second-line metastatic breast cancer (MBC).J Clin Oncol 28:15s, 2010 (suppl; abstr TPS135)