Trastuzumab combo may help in breast cancer refractory to trastuzumab alone

NEW YORK (Reuters Health) - Adding lapatinib to trastuzumab may improve progression-free survival in women whose HER2-positive metastatic breast cancer progressed on a previous trastuzumab regimen, according to a paper published online ahead of print in the Journal of Clinical Oncology.

"The study underscores how little we know about resistance to targeted therapies, as continuation of the drug was clearly beneficial despite overt (tumor) progression on previous treatment," Dr. Harold J. Burstein, one of the researchers, told Reuters Health by email.

He and his colleagues explain in their report that studies in HER2-positive cell lines showed a beneficial interaction between lapatinib and trastuzumab, suggesting that dual blockade would be more effective than a single agent.

Their phase 3 multicenter study involved 296 patients with HER2-positive breast cancer who had received a median of three prior trastuzumab-containing regimens for metastatic disease. Subjects were enrolled between November 2005 and November 2006, and they were randomly assigned to take lapatinib (1000 mg/day) in combination with trastuzumab (2 mg/kg IV per week, after a 4 mg/kg loading dose) or lapatinib alone. The median patient age was roughly 51 years.

On intent to treat analysis, the combination of lapatinib plus trastuzumab compared with lapatinib alone led to a significant improvement in progression-free survival (HR, 0.73; p = 0.008). Furthermore, the combination therapy produced a higher clinical benefit rate than lapatinib alone: 24.7% vs 12.4% (p = 0.01).

Specifically, the median progression-free survival was 8.1 weeks with lapatinib monotherapy and 12.0 weeks with the combination treatment.

There was also a trend for improved overall survival with the combination therapy (HR 0.75, p = 0.106). Even so, 39% in the combination arm and 48% in the monotherapy arm died by the data cutoff date. The median overall survival was 51.6 weeks with lapatinib plus trastuzumab, versus 39.0 weeks with monotherapy.

Adverse events led to treatment discontinuation in 11% of patients treated with combination therapy compared with 6% of patients treated with monotherapy.

"The study results support the habit that many oncologists have adopted of continuing to employ trastuzumab in multiple lines of treatment for advanced breast cancer," said Dr. Burstein.

The study was supported by GlaxoSmithKline, which markets lapatinib as Tyverb/Tykerb.

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