Tyverb in combination with capecitabine for HER2+ metastatic breast cancer EGF100151 pivotal study
Efficacy and safety from the EGF100151 registration study
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Tyverb (lapatinib) is an oral small molecule dual tyrosine kinase inhibitor that targets the ErbB1 (epidermal growth factor receptor) and HER2 receptors (human epidermal growth factor receptor type 2).
To compare Tyverb plus capecitabine with capecitabine alone in women with progressive, HER2-positive, advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline, a taxane and trastuzumab.
- Phase III, international, multicentre, randomised, open-label study involving 399 patients with HER2+ locally advanced or metastatic breast cancer who have progressed despite treatment with anthracyclines, taxanes and trastuzumab for metastatic disease.
- Women were randomised to treatment with Tyverb in combination with capecitabine (n=198) or capecitabine monotherapy (n=201).
- Tyverb was administered continuously at a dose of 1250 mg/day in combination with capecitabine 2000 mg/m2/day on Days 1–14 of a 21-day cycle. When used as monotherapy, the dose of capecitabine was 2500 mg/m2/day.
- The primary endpoint of independently assessed time to progression was 6.2 months with Tyverb–capecitabine combination therapy and 4.3 months with capecitabine alone (P=0.00013).
- The addition of Tyverb to capecitabine was associated with a 43% reduction in the risk of disease progression (hazard ratio: 0.57, 95% confidence interval 0.43–0.77; P=0.00013) compared with capecitabine monotherapy.
- Patients receiving Tyverb in combination with capecitabine had an increased overall response rate compared with those given capecitabine monotherapy (23.7% vs. 13.9%; P=0.017). The respective clinical benefit rates were 29.3% and 17.4% (P=0.008).
- The majority of adverse events were grade 1 or 2. Diarrhoea and rash were more common with Tyverb plus capecitabine treatment than with capecitabine alone.
- Reports of grade 3 and 4 adverse events were low and similar in both treatment arms. Serious hepatobiliary events were reported in 4 patients (1.9%) treated with Tyverb plus capecitabine and 3 patients (1.6%) treated with capecitabine alone.
- LVEF decreases were reported in 2.5% of patients treated with Tyverb plus capecitabine and 1.0% of patients treated with capecitabine alone. There were no withdrawals due to decreased LVEF in the combination arm.
- Serious adverse events resulted in 12 deaths, these included a cardiorespiratory arrest in the combination arm and a cardiac arrest and a respiratory arrest in the capecitabine arm.
When compared with capecitabine alone, the combination of Tyverb and capecitabine is superior in the treatment of women with advanced breast cancer whose tumours over-express HER2+ and who had progressed after treatment with regimens that included an anthracycline, a taxane and trastuzumab.
The Lapatinib Expanded Access Programme