PERTUZUMAB REVERSES TRASTUZUMAB RESISTANCE?

NEW YORK (Reuters Health) Feb 01 - When given with trastuzumab, pertuzumab, a HER2-targeted monoclonal antibody, can be an effective treatment for HER2-positive breast cancer that progressed during prior trastuzumab therapy, new research suggests.

By contrast, pertuzumab (rhuMAb 2C4) is probably not useful for HER2-negative disease, according to a separate study conducted by many of the same researchers.

Both papers appear in the February 1 Journal of Clinical Oncology.

The first study -- an open-label phase II trial led by Dr. Jose Baselga, from Vall d'Hebron University Hospital in Barcelona - involved 66 patients who received pertuzumab plus trastuzumab after disease progression with trastuzumab-based therapy. Along with trastuzumab, patients received pertuzumab in an 840-mg loading dose, followed by 420 mg every 3 weeks until disease progression or excessive toxicity.

Roughly 24% of patients had an objective response, defined as confirmed complete or partial responses. Fifty percent of patients had a clinical benefit, defined as the total number of objective responses plus stable disease >6 months. Complete response, partial response, and stable disease rates were roughly 8%, 17%, and 26%, respectively.

The median progression-free survival period was 5.5 months, the researchers note.

The drug combination was generally well tolerated, and side effects were mild to moderate. Cardiac toxicity was minimal and no patients discontinued therapy for cardiac-related reasons.

The authors note that single-agent pertuzumab is now being evaluated in the same patient population.

The second study, headed by Dr. Luca Gianni from Istituto Nazionale Tumori in Milan, assessed stable disease rates in 78 patients with HER2-negative metastatic breast cancer, all of whom received an 840-mg loading dose of pertuzumab. The patients were then randomized to continue with either 420 mg or 1050 mg given every 3 weeks.

Eighteen patients (44%) given 420 mg of pertuzumab and 14 (38%) given 1050 mg had stable disease lasting 12 weeks or longer. However, only 6 patients had a treatment response or stable disease lasting 6 months or more.

As in the first study, pertuzumab was generally well tolerated with minimal side effects. Eight patients had a potentially clinically relevant drop in cardiac function, including one with congestive heart failure.

"The limited efficacy observed in this study" and the "generally stable disease of relatively short duration" suggests there is little point to further studies of monotherapy with pertuzumab in unselected patients with HER2-negative breast cancer, the authors conclude.

Both studies were supported by F. Hoffmann-La Roche, which manufactures pertuzumab.

J Clin Oncol 2010.