A joint interim analysis of two studies of Trastuzumab ( Herceptin ) in early-stage breast cancer showed that HER2-positive breast cancer patients receiving Herceptin plus chemotherapy had a 52 percent reduction in the risk of disease recurrence compared to those patients who received chemotherapy alone

After four years in the study, 15 percent of women treated with Herceptin plus chemotherapy experienced disease recurrence, compared to 33 percent of women treated with chemotherapy alone.

Preliminary survival data showed a 49 percent improvement in overall survival ( or a hazard ratio of 0.67, which is equivalent to a 33 percent reduction in the risk of death ).

“ The reduction in disease recurrence observed in these trials was the largest improvement I’ve seen in breast cancer clinical research. Herceptin plus chemotherapy can potentially stop or delay early-stage HER2 ( human epidermal growth factor receptor 2 ) -positive breast cancer from relapsing, ” said Edith Perez, of the Mayo Clinic in Jacksonville, and the lead investigator in one of the two Herceptin trials. “ These trials also underscore the importance for every woman diagnosed with breast cancer to receive a HER2 test. ”

A preliminary safety analysis showed that adverse events in these studies were consistent with those seen in previous Herceptin clinical trials.
Each study had an independent external Data Monitoring Committee ( DMC ) that reviewed data from the studies, including cardiac safety data on a regular basis.

According to the investigators, serious or life-threatening ( and in rare cases, fatal ) cardiac events, most commonly congestive heart failure ( weakening of the heart muscle ) occurred approximately 3 to 4 percent more often in the Herceptin plus chemotherapy arms than in the chemotherapy alone arms.

In these studies, women with early-stage ( or cancer that has not spread beyond the breast and the associated lymph nodes ) HER2-positive breast cancer received Herceptin plus chemotherapy or chemotherapy alone following initial treatment with surgery and anthracycline and Cyclophosphamide ( AC ).

HER2-positive breast cancer is an especially aggressive form of the disease that affects approximately 25 percent of women with breast cancer.

The National Surgical Adjuvant Breast and Bowel Project ( NSABP ) study began enrollment in March 2000 and 2,085 patients have participated in the trial to date.
The North Central Cancer Treatment Group ( NCCTG ) study enrolled its first patient in June 2000 and 3,406 patients have participated to date.
Both studies are supported by the National Cancer Institute ( NCI ).
The joint interim analysis was based on data from 3,351 patients.
Each of the studies was a randomized, controlled trial that evaluated the combination of anthracycline and Cyclophosphamide (AC) followed by Paclitaxel chemotherapy, with or without Herceptin, using different treatment schedules of Paclitaxel in women with HER2-positive breast cancer.

Trastuzumab 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 who may be candidates for treatment with Herceptin.

Herceptin received 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 Paclitaxel 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 ).

Herceptin therapy does involve risks. 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 febrile neutropenia was 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: 41st Annual Meeting of the American Society of Clinical Oncology (ASCO), 2005


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