A Phase III study has shown that Lapatinib ( Tykerb ) and Capecitabine ( Xeloda ) versus Capecitabine alone nearly doubled time to progression ( 36.9 weeks in the combination arm versus 19.7 weeks with Capecitabine alone, p=0.00032 ) in women with refractory advanced or metastatic ErbB2 positive breast cancer whose disease had progressed following treatment with Trastuzumab ( Herceptin ) and other cancer therapies.
In April 2006, GlaxoSmithKline ( GSK ) stopped enrollment of the study based on the unanimous recommendation of an Independent Data Monitoring Committee ( IDMC ) because it had met its primary endpoint of time to disease progression, and exceeded the predetermined stopping criteria outlined in the committee charter.
Tykerb , a small molecule that is administered orally, inhibits the tyrosine kinase components of ErbB1 and ErbB2 receptors.
Stimulation of ErbB1 and ErbB2 is associated with cell proliferation and with multiple processes involved in tumor progression, invasion, and metastases.
Overexpression of these receptors has been reported in a variety of human tumors and is associated with poor prognosis and reduced overall survival.
“ Because ErbB2 positive breast cancer may eventually progress during or following treatment with Trastuzumab, there has been a need for an effective alternative treatment that can successfully block the function of ErbB2 in another way,” said Charles Geyer, at Allegheny General Hospital in Pittsburgh and principal investigator for this trial. “ These results indicate that Lapatinib can provide a needed alternative when Trastuzumab no longer appears to be helping to control the disease.”
The international, multicenter, open-label study ( EGF100151 ) enrolled 392 patients who had advanced or metastatic breast cancer with documented ErbB2 overexpression and whose disease progressed following treatment with Trastuzumab and other cancer therapies.
The interim analysis included 321 patients ( 160 in the Lapatinib-Capecitabine arm and 161 in the Capecitabine monotherapy arm ).
Discontinuation due to adverse events was 14 percent in the Lapatinib-Capecitabine combination arm versus 11 percent in the Capecitabine alone.
The commonest adverse events in the Lapatinib-Capecitabine arm included diarrhoea, hand-foot syndrome and rash.
An asymptomatic relative decrease of greater than or equal to 20 percent in left ventricular ejection fraction ( LVEF ) occurred in 2.5 percent of patients on the combination arm and less than 1 percent of patients on Capecitabine; all patients recovered normal LVEF.
Source: 2006 American Society of Clinical Oncology (ASCO) Annual Meeting