CHICAGO--A monoclonal antibody expected to be approved by the FDA before years end is as potent as taxane therapy in certain virulent refractory breast cancers, according to research presented at an integrated symposium at the 34th Annual Meeting of the American Society of Clinical Oncology.
Melody A. Cobleigh, MD, reported an overall response rate of 15% in patients with metastatic breast cancer whose tumors overexpress the HER2/neu oncogene. The new drug is trastuzumab(Drug information on trastuzumab) (Herceptin), a humanized anti-HER2 monoclonal antibody developed by Genentech, Inc.
In a related study, other researchers reported that trastuzumab used in combination with standard chemotherapy significantly improves both response rate and response durability in this type of high-risk breast cancer .
Dr. Cobleigh and her colleagues at Rush Cancer Institute studied trastuzumab in an open-label trial of 222 women with HER2 overexpressing metastatic breast cancer. She said these were "extremely refractory patients." All had progressive disease during one or two previous chemotherapy regimens.
"Ninety-two percent had progression during a doxorubicin(Drug information on doxorubicin)-containing regimen, two-thirds had progression during taxane therapy, and 9% had already had high-dose chemotherapy with autologous bone marrow or stem cell rescue," she said.
Patients received a 4 mg/kg loading dose of trastuzumab and then a weekly dose of 2 mg/kg.
After a median follow-up of 11 months, the overall response rate was 15%, including 6 confirmed complete responses and 25 partial responses. The Kaplan-Meier estimate of the median response duration is 9.1 months. Median time to progression was 3.1 months.
Median survival is 13 months, "which compares favorably with an anticipated survival of 8 months in a similar population treated with chemotherapy," Dr. Cobleigh said.
Dr. Cobleigh reported two main types of adverse effects. At the first infusion of antibody, about 40% of patients developed an infusion-related symptom complex, including fever, chills, asthenia, pain at the tumor site, nausea, vomiting, and headache.
The typical presentation is a patient who is pale and shaking. "Dont be scared," she advised. "Reassure the patient that these symptoms will go away. Turn off the infusion. Give Benadryl and acetaminophen. Then restart the infusion at a slower rate."
A more serious problem is treatment-related cardiac dysfunction. Ten of 213 patients (5%) developed problems resembling myotoxicity caused by anthracyclines. This included a reduction of 10% or more in cardiac ejection fraction. These problems responded to treatment, and most patients were able to continue trastuzumab.
The mechanism behind this problem is unknown. It appears to be more common in patients treated with doxorubicin or other anthracyclines, but one of Dr. Cobleighs patients with this effect reportedly had no prior doxorubicin exposure.
Direct cardiotoxicity is unlikely, but Dr. Cobleigh did point out that although there are no HER2 receptors in the heart, there are HER4 receptors. These receptors may be similar enough to react in some way with the antibody.
Immune reactions are always a concern with antibody therapy, but there seems to be little risk with trastuzumab. Neutralizing antibody against trastuzumab was seen in only 1 of about 900 patients who have been treated with the antibody. "This is a very effective, very safe drug for women with extremely refractory breast cancer," she concluded.