Trastuzumab is a medication used in treatment of metastatic breast cancer. Trastuzumab targets the HER2 signaling pathway to reduce proliferation and survival of cancerous cells. The drug is FDA approved and many clinical trials have been conducted to test its safety and efficiency. Breast cancers that detect a high copy of HER2 gene are the most eligible candidates for treatment with Trastuzumab. Let us take a look at the results of some of the significant clinical trials conducted for Trastuzumab.
Clinical Trials for Trastuzumab – An Overview
- In the first Phase 2 Trial of Trastuzumab, 46 women with previously treated metastatic breast cancer and tumors took part. These cancers expressed HER2 at +2 or +3 levels. The trial began with 250mg of the drug being used as loading dose, followed by 100mg of drug administered every week for 10 weeks. This allowed serum antibody concentration to be maintained at 10µg/milliliter. Treatment continued until toxic effects or progression of disease occurred. 12% of patients responded to treatment with Trastuzumab proving that drug was indeed effective against some patients. A multicenter phase2 trial also showed similar results. The modest response rates were attributed to many factors including the fact that patients with cancers that tested +2 immunostaining for HER2 were included.
- Subsequent randomized trials proved that dose escalation did not increase response rate. 114 patients with metastatic breast cancer participated in the trials. The loading dose of the drug was 4mg/kg of body weight, followed by 2mg/kg every week. The response rate was recorded at 35% and this was higher in patients who had not undergone chemotherapy compared to those who had some kind of therapy (antiestrogen, Trastuzumab, etc). The results of this trial suggested that Trastuzumab could be used as s single agent before going in for conventional chemotherapy.
- A pivotal randomized clinical trial was conducted which demonstrated the activity of Trastuzumab in conjunction with chemotherapy. 469 patients enrolled for the trial. They had previously detected HER2 positive metastatic breast cancer that were not treated. Patients were grouped into two, with one group receiving conventional chemotherapy alone, while other group was given both drug and chemotherapy. HER2 expression was monitored using immunohistochemical staining. When patients receiving only chemotherapy demonstrated a progression in disease they were given Trastuzumab, while patients on the drug were administered the same on discretion of the physician. Results indicated that:
- Time required for disease progression increased from 4.6 months in group receiving only chemotherapy to 7.4 months among those who received both.
- Patients who received drug showed increased response rate.
- In addition, they also recorded response for longer timer.
- Patients who received both demonstrated a lower death rate along with 20% reduction in risk of death.
Various nonrandomized trials have shown that Trastuzumab is relatively safe and can be used in combination with chemotherapeutic agents used in conventional treatment of breast cancer.
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