Lapatinib: A competitor or companion to trastuzumab?
Received 1 March 2009; received in revised form 9 June 2009; accepted 11 June 2009. published online 14 September 2009.
Summary
Trastuzumab (Herceptin), a monoclonal antibody against HER2 has established itself as the treatment paradigm of HER2-overexpressing breast cancer. Its success, however, has been tempered by its sequelae. In particular, most tumours become resistant to trastuzumab through a variety of mechanisms. Furthermore, there is both an increased incidence of cardiac dysfunction and a worrying pattern of CNS metastasis associated with trastuzumab. To manage these concerns, many new treatments targeting HER2 have been developed. Of these emerging therapies, the dual tyrosine kinase receptor inhibitor against EGFR and HER2, lapatinib (Tyverb/Tykerb) has shown the most promise to date. Encouraging early results in vitro have now been reproduced in phase II/III clinical trials, both as lapatinib monotherapy and synergistically with other established therapeutic regimes, including trastuzumab itself. Trial results suggest it may be of considerable benefit to patients with trastuzumab-resistant tumours and may play a role in the reduction of CNS relapses. In addition, lapatinib is well-tolerated and unlike trastuzumab, minimal cardiac dysfunction has been documented. A number of trials are underway to assess whether lapatinib will oust trastuzumab from its pole position in the management of HER2-positive breast cancer or whether their combination will prove to be superior to either therapy alone.
aEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland
bDepartment of Surgery, Beaumont Hospital, Beaumont Road, Dublin, Ireland
Corresponding author. Address: Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, York House, 123 St. Stephens Green, Dublin 2, Ireland. Tel.: +353 14028515.