LAPATINIB-TRASTUZUMAB COMBINATION NOT READY YET 

July 16, 2012 — A registration application for the use of dual HER2inhibition in the treatment of metastatic breast cancer has been pulled in the United States.

GlaxoSmithKline has withdrawn an application for approval from the US Food and Drug Administration (FDA) for a new indication for its HER2 inhibitor lapatinib (Tykerb). The new indication would have extended the use of lapatinib, in combination with another HER2 inhibitor, trastuzumab (Herceptin, Roche), in patients with metastatic breast cancer with a high expression of HER2 who had already been treated with trastuzumab alone and who had disease progression.

This new indication was to have been discussed by the FDA Oncologic Drugs Advisory Committee this week, but the meeting has now been cancelled.

GlaxoSmithKline said that its discussions with the FDA "highlighted questions that could not be addressed with the data currently available," so the company decided to withdraw the application and wait for the results of ongoing clinical trials.

However, similar applications in other countries and in Europe have not been withdrawn.

Synergistic Combination

Data from a phase 3 trial, first presented at the 2008 annual meeting of the American Society of Clinical Oncology, showed that lapatinib plus trastuzumab had synergy when used together. The combination improved clinical outcomes in patients who had progressed on trastuzumab alone, without a substantial change in the adverse-effect profile, noted lead author Joyce O'Shaughnessy, MD, from the Baylor-Sammons Cancer Center, in Dallas, Texas. She suggested that the combination might "provide a chemotherapy-free option" for women with metastatic HER2-positive breast cancer.

Although both drugs act to block HER2, they do so in different ways. Trastuzumab (an injectable monoclonal antibody) is a large-protein molecule that targets the part of the HER2 protein on the outside of the cell, whereas lapatinib (an oral drug) is a smaller molecule that enters the cell and blocks the intracellular function of this and other proteins.