GlaxoSmithKline announced that positive data from three key studies on its first-in-class, oral small molecule HER2 kinase inhibitor, Tykerb (lapatinib). Results of these and other important Tykerb studies are being presented this week at the 2007 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois. The use of Tykerb in these settings is investigational.

"The robust clinical data presented for Tykerb at ASCO further demonstrate the great potential of this drug as an essential component of treatment regimens for women with HER2-positive breast cancer," said Paolo Paoletti, M.D., senior vice president of the Oncology Medicine Development Center at GSK. "GSK is dedicated to an ongoing Tykerb clinical programme to identify additional treatment regimens, as well as patient populations that may respond to Tykerb. The data presented at ASCO week underscore our unrelenting commitment to improving treatment for these patients."

Tykerb in Combination with Paclitaxel as first-line treatment for patients with Metastatic relapsed advanced breast cancer.

Paclitaxel is one of the most commonly used chemotherapies in breast cancer. Therefore, the evaluation of Tykerb in combination with this treatment is of high importance.

This large, randomized, multicenter, prospective trial evaluated a total of 580 patients either negative or untested for HER2 over expression. While the combination therapy did not demonstrate an incremental benefit for patients with HER2-negative disease, an analysis of 91 patients who were retrospectively identified as having HER2-positive disease showed that TYKERB plus paclitaxel increased progression-free survival in patients with HER2-positive breast cancer not previously treated with trastuzumab.

Data from this trial of Tykerb plus paclitaxel versus paclitaxel alone as first-line treatment in patients with newly diagnosed metastatic breast cancer have provided the first evidence of activity in the HER2-positive subgroup that the combination significantly improves progression-free survival of the disease compared with the chemotherapy alone.

"These results have the potential to directly impact clinical practice and may benefit patients in the first-line treatment setting," said Dr Angelo Di Leo, director of the Medical Oncology Unit, Hospitalof Prato(Italy) and lead investigator of this trial. "Tykerb in combination with paclitaxel is a step in the right direction as the oncology community explores potential combination therapies to individualise treatment for breast cancer patients."

The most common adverse events (AEs) included rash, diarrhoea, nausea, vomiting, neutropenia and mucositis. The addition of Tykerb to paclitaxel resulted in an increase in diarrhoea and rash. SAE-related deaths were higher in the combination arm.

Several additional phase III trials combining Tykerb with taxanes are being conducted in patients with HER2-positive disease.

"There is a significant need for effective alternatives to prevent and treat brain metastases arising from breast cancer as there are no currently approved systemic treatments for these patients. These data suggest that Tykerb may cross a compromised blood brain barrier and suggest the CNS activity of tykerb," said Nancy U. Lin, M.D.,