GlaxoSmithKline begins phase 2 trial of Tykerb in cancer patients

By Angela McDaniels

Seattle, Dec. 9 - GlaxoSmithKline said it has begun a global multicenter phase 2 trial to evaluate Tykerb (lapatinib) for the treatment of ErbB2-overexpressing breast cancer that has metastasized to the brain.

The multi-center trial will assess the safety and efficacy of Tykerb therapy by monitoring lesions in the brain using magnetic resonance imaging and through a centralized radiological review.

Other treatment endpoints include reduction in tumor-related neurological symptoms, duration of response to therapy, time to progression at any site and overall survival.

The study will soon begin enrolling 220 patients with breast cancer who have progressive brain metastases following cranial radiotherapy and prior Herceptin (trastuzumab)-based therapy, the company said.

Patients will be separated into two cohorts: (1) patients able to carry out most daily activities and who have received one or two prior Herceptin-containing regimens and (2) patients ambulatory and capable of self-care but unable to carry out any work activities or who have received more than two prior Herceptin-containing regimens.

Herceptin-based regimens have improved both systemic control and overall survival in patients with metastatic ErbB2-overexpressing breast cancer, the company said. However, it may not cross the blood-brain barrier and ErbB2-overexpressing breast cancer may have a predilection for metastases to visceral sites including the brain.

As a result, central nervous system disease progression is emerging as a significant clinical problem in this patient population, the company said.

About 20% of breast cancer patients with metastatic or stage IV disease are diagnosed with brain metastases, and autopsy data suggests a true incidence of nearly 30%. Retrospective analyses have disclosed a 28% to 43% incidence of brain metastases among women treated with Herceptin for stage IV ErbB2-overexpressing breast cancer across multiple institutions, the company said.

Preliminary evidence of activity with Tykerb as a first-line treatment has been observed in ongoing clinical trials of ErbB2-overexpressing breast cancer brain metastases, the company said.

Tykerb is an orally bioavailable small molecule which potently inhibits two receptors, ErbB2 and ErbB1. Stimulation of ErbB1 and ErbB2 is associated with cell proliferation and with multiple processes involved in tumor progression, invasion and metastasis, the company said.

GlaxoSmithKline is a pharmaceutical company with U.S. operations in Philadelphia and Research Triangle Park, N.C.

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