ATLANTA ? For women with HER2-positive breast cancer who develop Herceptin (trastuzumab) resistance, the investigational drug Tykerb (lapatinib) in combination with Xeloda (capecitabine) essentially doubles time to progression compared with Xeloda monotherapy, investigators reported here.
ATLANTA, June 3 ? For women with HER2-positive breast cancer who develop Herceptin (trastuzumab) resistance, the investigational drug Tykerb (lapatinib) in combination with Xeloda (capecitabine) essentially doubles time to progression compared with Xeloda monotherapy, investigators reported here.
That was the major finding of a phase III open-label study that randomized 160 women with HER2-positive breast cancer to the combination and 160 women to Xeloda monotherapy. The results were presented today at a special session at the American Society of Clinical Oncology meeting.
The median time to progression was 36.9 weeks for women who received Tykerb plus Xeloda versus 19.7 weeks for women receiving Xeloda alone, which was a hazard ration of 0.51 (95% confidence intervals 0.35-0.74, P value = 0.00016).
"This is an effective treatment that should be considered the new standard of care," said Charles E. Geyer Jr., M.D., director of breast cancer medical oncology at Allegheny General Hospital in Pittsburgh the study's principal investigator.
All women had previously been treated with anthracyclines, taxanes, and Herceptin. They were randomized to Tykerb 1,250 mg/d continuously plus Xeloda 2,000 mg/m2 /d at days one to 14 every three weeks or Xeloda 2500 mg/m2 /d days one to 14 every three weeks.
Tykerb, also known as GSK572016, is being developed by GlaxoSmithKline for treatment of solid tumors. It is a tyroxine kinase inhibitor of components of epidermal growth factor receptor (EGFR) receptors and HER2 receptors.
Julie Gralow, M.D., of the University of Washington and Fred Hutchinson Cancer Center in Seattle said ASCO was "expecting an announcement this weekend about increased availability of this agent while it is in development."
Dr. Gralow, who was not involved in the trial, chaired a press conference where the data were reported.
The finding was significant because while the chemotherapy agent can be changed when women become resistant to Herceptin, Dr. Gralow said, "There are no other targeted therapies available when Herceptin doesn't work."
Dr. Geyer said the trial was halted last March 20 on the unanimous recommendation of the independent data monitoring committee "based on clinically meaningful, statistically significant advantage in primary endpoint at planned interim analysis."
Asked to predict the potential impact of the drug if approved, Dr. Geyer said "Eventually every women treated with Herceptin will develop resistance, so it is likely that all of those women would be treated with [Tykerb]."
Another plus for Tykerb is that there has not yet been any evidence of cardiovascular complications, which have been reported with Herceptin. "Declines in left-ventricular ejection fraction were infrequent, asymptomatic, and reversible," Dr. Geyer said.
The Tykerb-Xeloda combination increased diarrhea, but most of the increase was in grade 1 toxicities, Dr. Geyer said. There was also a slight increase in reports of hand-foot reactions, which has been previously reported with Xeloda.
Dr. Gralow said the study results were available too late be included in the late-breaking clinical trials session, so Dr. Geyer presented at a special scientific session, and there was no published abstract.