ASCO: Trastuzumab Tops Lapatinib for First-Line Treatment of HER2-Positive Metastatic Breast Cancer

Women with metastatic HER2-positive breast cancer treated with a taxane-based chemotherapy in combination with trastuzumab as a first-line of treatment have a longer progression-free survival compared to chemotherapy in combination with lapatinib (Tykerb). This is the interim result of an open-label NCIC phase III clinical trial. An independent review recommended release of the trial as the superiority boundary was crossed.

Dr. Gunter von Minckwitz

The primary endpoint, progression-free survival, was 8.8 months in the lapatinib-treated group compared to 11.4 months for the trastuzumab-treated group (hazard ratio, 1.33, P = .01). Overall survival, a secondary endpoint, was not different between the two study arms (P = .62).

Gunter von Minckwitz, Chairman of the German Breast Group and professor of gynecology at the University of Frankfurt in Germany, who discussed the data presentation, highlighted that the results do not provide information on the efficacy of lapatinib in patients who were more heavily pretreated in an adjuvant setting.

This is the first study that has directly compared the efficacy of lapatinib to trastuzumab, in combination with a taxane-based chemotherapy in a front-line setting. The trial compared either paclitaxel or docetaxel, with either lapatinib (Tykerb) at a dose of 1,250 mg per day or trastuzumab at a dose of 6 mg/kg every 3 weeks.

“This study confirms the need for head-to-head trials in the metastatic setting prior to mounting adjuvant studies,” said  Karen A. Gelmon of the British Columbia Cancer Agency–Vancouver Cancer Centre. Dr. Gelmon presented the trial results of the 656-patient trial at the annual meeting of the American Society of Clinical Oncology.

Lapatinib is an oral, dual tyrosine kinase inhibitor that works by inhibiting the HER2 receptor pathway and epidermal growth factor receptor (EGFR). Lapatinib is approved for treatment of HER2-overexpressing advanced breast cancer in combination with capecitabine after treatment with chemotherapy and trastuzumab. The drug was granted an accelerated approval for the treatment, in combination with letrozole (Femara), of postmenopausal women with hormone-receptor positive metastatic breast cancer whose tumors also overexpress HER2.

More high-grade diarrhea and rash was experienced by patients taking lapatinib compared to trastuzumab that was statistically significant. Other adverse events were low-grade and similar between the two treatment regiments and no new toxicities were seen (P < .001). In the lapatinib arm, 17.8% of patients discontinued treatment due to toxicity compared to 10.6% of patients in the trastuzumab arm.

Dr. von Minckwitz stated that there is now increasing evidence of lower lapatinib activity compared to trastuzumab in different breast cancer settings. He speculated that while patients given lapatinib show an initial high efficacy, this may be hindered due to the rapid acquirement of secondary resistance.

The final analysis including quality of life analysis, central nervous system metastasis, and objective response rates will be presented at a conference later this year, likely at the San Antonio Breast Cancer Symposium.

The trial was funded by GlaxoSmithKline, the maker of lapatinib, and the Canadian Cancer Society Research institute.