Two Phase III trials of Herceptin ( Trastuzumab), a monoclonal antibody, were stopped early after a preliminary joint interim analysis demonstrated an improvement in disease-free survival and in overall survival.

The trials compared Herceptin plus chemotherapy to chemotherapy alone as adjuvant therapy following initial treatment with surgery for women with early-stage human epidermal growth factor receptor 2 ( HER2 ) positive breast cancer.

The two studies were sponsored by the National Cancer Institute ( NCI ), part of the National Institutes of Health ( NIH ), and conducted by a network of researchers led by the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) and the North Central Cancer Treatment Group ( NCCTG ), who conducted this prospectively-designed joint interim analysis following consultation with the FDA.

The NCCTG study has enrolled 3,406 patients to date; the NSABP study has enrolled 2,085 patients to date.

The interim analysis was based on information from 3,300 patients.
These studies will stop enrolling new patients and the cooperative groups will continue to monitor patients for longer-term data.
Each of the studies was a randomized, controlled trial that evaluated the combination of anthracycline and Cyclophosphamide, followed by Paclitaxel, with or without Herceptin using different treatment schedules of Paclitaxel in women with HER2-positive breast cancer.

Adverse events in these studies were consistent with those seen in previous Herceptin clinical trials. There were three to four percent more cases of serious or life-threatening ( and in rare cases, fatal ) cardiac events, most commonly congestive heart failure in patients receiving the combination of Herceptin plus chemotherapy.

Herceptin is a targeted therapeutic antibody treatment for women with HER2-positive metastatic breast cancer.
Special testing is required to identify women who are HER2-positive and candidates for treatment with Herceptin.

Herceptin received U.S. Food and Drug Administration ( FDA ) approval in September 1998 for use in women with metastatic breast cancer who have tumors that overexpress the HER2 protein.
It is indicated for weekly treatment of patients both as first-line therapy in combination with Paclitaxel and as a single agent in second- and third-line therapy.

In clinical trials, Herceptin has shown a survival benefit when used in combination with chemotherapy. In December 2001, Genentech received FDA approval to include data that showed a 24 percent increase in median overall survival for women with HER2-positive metastatic breast cancer treated initially with Herceptin and chemotherapy compared to chemotherapy alone ( median 25.1 months compared to 20.3 months ).

Serious side effects have occurred in patients treated with Herceptin in metastatic breast cancer.
Herceptin administration can result in the development of ventricular dysfunction and cardiac failure. Severe hypersensitivity reactions ( including anaphylaxis ), infusion reactions, and pulmonary events have been infrequently reported. Rarely, these were fatal.

Serious reactions were treated by discontinuing Herceptin and administering supportive therapy.
In clinical trials, the incidence and severity of cardiac dysfunction was highest in patients receiving Herceptin with anthracycline and Cyclophosphamide.
Most patients responded to medical therapy, including discontinuation of Herceptin. However, some patients were successfully managed while continuing Herceptin therapy.
Patients receiving Herceptin should be monitored for deteriorating cardiac function.

In clinical trials, approximately 40 percent of patients experienced symptoms such as chills and fever during the first infusion.
These and other symptoms, including nausea, vomiting, and pain, occurred infrequently with subsequent infusions.
In clinical trials, the incidence of moderate to severe neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those receiving chemotherapy alone.
There was an increased incidence of anemia, leukopenia, diarrhea, and infection when Herceptin was used in combination with chemotherapy.

Source: Genentech, 2005


XagenaMedicine2005