FDA Okays Lapatinib (Tykerb) for Treatment-Resistant Breast Cancer

ROCKVILLE, Md., March 13 -- The FDA today approved lapatinib (Tykerb), an oral kinase inhibitor that targets HER2-positive tumors, for treatment-refractory metastatic breast cancer, to be used in combination with capectabine (Xeloda).

The FDA said lapatinib-capectabine combination is indicated for women who have received prior therapy with anthracycline chemotherapy and trastuzumab (Herceptin).

In clinical trials the duo led to a statistically significant improvement in the time to tumor progression over capectabine alone in women with HER2-positive metastatic disease and to a higher rate of tumor response (24% vs. 14%). Mortality data wee described as "not yet mature."

Lapatinib, a new molecular entity, is the yin to trastuzumab's yang. Trastuzumab, which was the first molecular targeted therapy to win FDA approval, is a large protein molecule that targets HER2 receptors on the outside of the cell. By contrast, lapatinib is a small molecule that penetrates the cell and homes in on a number of proteins including HER2.

These differences in mechanism of action explain the efficacy of lapatinib in women who have become resistance to trastuzumab, said the FDA.

Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research, called the lapatinib approval "a step forward in making new treatments available for patients who have progression of their breast cancer after treatment with some of the most effective breast cancer therapies available."

The FDA said the lapatinib approval was based on a randomized clinical trial in about 400 women with advanced or metastatic HER2 positive breast cancer. In the trial, half the patients received lapatinib with capecitabine and half received capecitabine alone. Lapatinib, which is formulated in 250 mg tablets, was given in an undivided dose of 1,250 mg once daily for 21 days and in combination with capecitabine on days 1-14 of a 21-day cycle.

Tykerb Plus Chemotherapy Slows Advance of Metastatic Breast Cancer http://www.medpagetoday.com/HematologyOncology/BreastCancer/tb/4773

The most commonly reported lapatinib-related side effects included diarrhea, nausea, vomiting, rash and hand-foot syndrome which may include numbness, tingling, redness, swelling and discomfort of hands and feet. Generally reversible decreases in heart function were also reported in a small percentage of patients.

Lapatinib will be marketed by GlaxoSmithKline.