Tyverb in combination with capecitabine for HER2+ metastatic breast cancer EGF100151 pivotal study
Interim results of the EGF100151 registration study
Geyer C, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–2743.
The combination of the anti-HER2 tyrosine kinase inhibitor Tyverb (lapatinib) capecitabine has shown to be active in women with HER2-postitive metastatic breast cancer who have progressed after trastuzumab-based therapy. Further validation was required.
To assess the clinical effects of Tyverb in combination with capecitabine versus capecitabine alone in the treatment of women with HER2-positive metastatic breast cancer.
- Interim analysis of a multicentre, randomised, open-label, phase III clinical trial involving 324 women randomised up to that time-point to receive either to Tyverb plus capecitabine (n=163) or capecitabine monotherapy (n=161).
- The women had HER2-positve, locally advanced breast cancer (a T4 primary tumour and stage IIIB or IIIc disease) or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline, a taxane and trastuzumab.
- Combination treatment consisted of Tyverb, administered at a dose of 1250 mg daily and given 1 hour before or after eating breakfast, and capecitabine, given at a dose of 2000 mg/m2 in two divided doses on Days 1–14 of a 21-day cycle. When given as monotherapy, capecitabine was given at a dose of 2500 mg/m2 in two divided doses on Days 1–14 of a 21-day cycle.
- The primary endpoint was independently assessed time to progression (TTP). Interim analysis (n=324) met specified criteria for reporting the trial results early. Results given below have since been superseded by later a dataset published in 2008.
- The median TTP was 8.4 months with Tyverb–capecitabine combination and 4.4 months with capecitabine monotherapy (hazard ratio 0.47, 95% confidence interval 0.32–0.68; p<0.001).
- Secondary endpoints included progression-free survival (PFS), overall survival (OS), the overall response rate (ORR) and safety.
- The median PFS was 8.4 months for Tyverb plus capecitabine and 4.1 months for capecitabine alone (p<0.001). This interim result has subsequently been superseded by results published in 2008 and 2010.
- OS was similar with 36 deaths (22%) in the Tyverb–capecitabine arm and 35 deaths (22%) in the capecitabine monotherapy arm.
- The ORR was 22% for combined treatment with Tyverb and capecitabine and 14% for capecitabine monotherapy (p=0.09).
- The rate of clinical benefit (complete response, partial response or stable disease for at least 6 months) was 27% in the Tyverb plus capecitabine arm and 18% in the capecitabine monotherapy arm.
- The most common adverse events were diarrhoea, hand–foot syndrome, palmar plantar erythrodysaesthesia, nausea, vomiting, fatigue and rash that was distinct from PPE.
- Adverse events led to treatment discontinuation in 22 of women (13%) in the combination therapy arm and 18 of women (12%) in the capecitabine alone arm.
The combination of Tyverb and capecitabine achieved superior TTP to capecitabine alone in women with HER2+ advanced breast cancer who had progressed after treatment with regimens that included an anthracycline, a taxane and trastuzumab.
The Lapatinib Expanded Access Programme