Anticancer antibody - pertuzumab
The HER2 human epidermal growth factor receptor has become well known as the target for Roche's breast cancer drug Herceptin (trastuzumab). It is now a standard treatment in the subsection of breast cancers that are HER2 positive, but it works well only in those cancers that have a high level of HER2 expression.
The HER2 human epidermal growth factor receptor has become well known as the target for Roche's breast cancer drug Herceptin (trastuzumab). It is now a standard treatment in the subsection of breast cancers that are HER2 positive, but it works well only in those cancers that have a high level of HER2 expression.
Another monoclonal antibody that targets HER2, pertuzumab, is being developed by Genentech and Roche.1 However, it binds to a different HER epitope, which makes it active even in cancers that are low expressers of HER2.
The antibody is being investigated as a potential treatment for a number of different cancers, including breast, lung, ovarian and prostate. In one Phase II trial, 123 patients were treated in a single agent study.2 Five partial responses were achieved, and a further 32 subjects achieved stable disease.
It has also been evaluated in metastatic breast cancer with low levels of HER2 expression.3 In the first arm of the randomised trial, 41 patients were given an intravenous loading dose of 840mg of the antibody, followed by a further 420mg every three weeks. The 37 subjects in the second arm were given 1050mg every three weeks. In all, six of the 78 patients either had a response or achieved stable disease for at least six months. Although the response rate in HER2 negative breast cancer was low, it could have possibilities for this indication in combination with other drugs.
Another trial has been carried out in prostate cancer patients whose disease had progressed after taxane therapy.4 A total of 41 patients were given a loading dose of 840mg, followed by 420mg every three weeks. There were no complete or partial responses, but five patients achieved stable disease for at least 23 weeks; retrospective analysis indicated that pertuzumab prolonged survival.
The drug has also been investigated in combination with trastuzumab in HER2 positive breast cancer patients who are resistant to trastuzumab alone.5 Subjects were given 8 or 6mg/kg trastuzumab and 840mg pertuzumab as a loading dose, and then 6mg/kg trastuzumab and 420mg pertuzumab every three weeks. A total of 11 patients received 64 cycles of treatment. The objective response rate was 18%, two patients had partial responses, three had stable disease, and six had disease progression. Cardiac toxicity was also observed, although it was largely unsymptomatic. However, the regime may prove of benefit in some patients for whom trastuzumab is not working.