According to results recently presented at the 2006 annual San Antonio Breast Cancer Symposium (SABCS), the addition of Tykerb (lapatinib) to Xeloda® (capecitabine) improves progression-free survival compared to Xeloda alone in the treatment of HER2-positive, advanced refractory or metastatic breast cancer.

Tykerb is an oral small molecule that targets both ErbB1 and ErbB2 tyrosine kinases. Tykerb has demonstrated activity in HER2-positive breast cancers and continues to be evaluated in different patient populations. 

Researchers from England and the Allegheny General Hospital in Pennsylvania recently conducted a clinical trial to compare Tykerb plus Xeloda to Xeloda alone in the treatment of HER2-positive breast cancer patients. Data from this trial included 321 patients who had HER2-positive refractory advanced or metastatic breast cancer. Patients had received, at minimum, prior therapy with an anthracycline, taxane, and Herceptin® (trastuzumab). Patients were randomized to receive Tykerb (1250 mg once daily) with Xeloda (2000 mg/m2/day on days 1-14, every 21 days) or Xeloda 2500 mg/m2/day on days 1-14, every 21 days. 

• Median time to progression was 36.7 weeks for patients on combination therapy, compared with 19.1 weeks for patients on monotherapy (HR=.49)
• Median progression-free survival was 36.7 weeks for patients on combination therapy, compared with 17.9 weeks for patients on monotherapy (HR=.48).
• Diarrhea was more common among patients treated with Tykerb/Xeloda (58%) compared with patients treated with Xeloda (39%); this difference was due to grade I diarrhea.
• HER-2 positivity on FISH was correlated with an increased response to Tykerb (p=0.005)

Increased levels of the HER2 extracellular domain (HER2 ECD) conferred a poorer progression-free survival among patients treated with Xeloda alone; conversely, increased HER2 ECD levels did not confer changes in progression-free survival among patients treated with combination therapy. 

The researchers concluded that the addition of Tykerb to Xeloda significantly improves median time to progression and progression-free survival compared to Xeloda alone in HER2-positive, advanced refractory or metastatic breast cancer.  Researchers will continue to evaluate biomarkers and potential markers of resistance to Tykerb.

Reference: Cameron D, Stein S, Zaks T, et al. Lapatinib plus Capecitabine Shows Superior Efficacy Compared to Capecitabine Alone in Patients with ErbB2 Positive Advanced or Metastatic Breast Cancer- Initial Biomarker Data. Proceedings from the 29th Annual San Antonio Breast Cancer Symposium (SABCS). San Antonio, Texas. Oral presentation December 15, 2006. Abstract 2. 

Related News 

Tykerb® Effective in Inflammatory Breast Cancer (12/20/2006)

Phase II Trial Suggests that Tykerb® is Active in Inflammatory Breast Cancer (06/05/2006)

Phase III Trial of Tykerb® Produces Promising Results in Refractory or Metastatic Breast Cancer (06/04/2006)