Pembrolizumab in Triple Negative Metastatic Breast Cancer

Pembrolizumab in Triple Negative Metastatic Breast Cancer

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Highlights:
  • Pembrolizumab is used for the treatment of several cancers like squamous cell cancer, malignant melanoma, classical Hodgkin's lymphoma, and non-small cell lung cancer
  • Researchers are evaluating the drug for the treatment of triple negative metastatic breast cancer
  • Initial results are promising, though further studies are needed
Pembrolizumab, an immune-based treatment, may be effective in treating triple negative breast cancer that has spread to distant sites, irrespective of whether the patient had received prior treatments for the cancer, finds a new study.
Pembrolizumab in Triple Negative Metastatic Breast Cancer

The results of the study, which was conducted in 17 centers in 4 continents, were presented at the annual meeting of the American Society of Clinical Oncology in Chicago.

Breast cancer is a major killer in women the world over. Despite attempts by health organizations to create awareness, screening methods to detect the cancer early, and the availability of effective and safe medications, there are still a large number of women who present with the cancer at a late stage when it has spread beyond the breast, often with fatal consequences. It is therefore important that effective treatment options should be developed for late stages, to improve survival in these patients as well.

Triple negative breast cancer is a type of breast cancer that lacks three well categorized molecular components, the progesterone receptors, the estrogen receptors and the HER-2 receptors. These cancers do not respond to hormonal treatments like Tamoxifene or HER-2 receptor blockers like Trastuzumab. They can however be treated with chemotherapy medications, radiation and/or surgery. Efforts are being made to increase the number of treatment options for these patients.

The research team are evaluating the use of the monoclonal antibody pembrolizumab in the treatment of metastatic triple negative breast cancer. Monoclonal antibodies are protein molecules produced in the laboratory.

Pembrolizumab has already been approved by the US Food and Drug Administration for the treatment of a variety of cancers including skin cancers like squamous cell cancers of the head and neck, malignant melanoma, classical Hodgkin's lymphoma (which is a type of blood cancer), and non-small cell lung cancer. Adverse effects include fatigue, high blood glucose levels, reduced blood counts, itching and liver enzyme abnormalities. Pembrolizumab prevents the binding of programmed cell death-1 (PD-1) receptors on cancer cells with PD-1 ligands (PD-L1 and PD-L2). It thus prevents the suppression of the immune system caused by the binding, and allows the immune system to attack the cancer cells.

In a clinical trial sponsored by the makers of pembrolizumab, researchers administered 200 mg of pembrolizumab every three weeks to patients with triple negative breast cancer that had spread to other sites (referred to as "metastatic"). The patients received the treatment for 24 months or until the disease continued to progress despite treatment, the patient experienced intolerable toxicity, or due to a decision taken by the investigator or the patient. Imaging tests to evaluate the cancer were carried out every 9 weeks during the first year of treatment, and every 12 weeks thereafter.

In the first group called cohort A, the research team tested the drug in 170 patients who were previously treated with other medications. The patients were included in this group regardless of PD-L1 expression in their cancer cells. The researchers found the following effects of the treatment:
  • The tumors shrank by more than 30 percent in 5% patients. These patients survived for at least a year following the treatment
  • The cancer stabilized in 21% patients
  • Severe side effects were experienced by 12% patients. Seven patients discontinued the treatment due to the side effects
In the second group called Cohort B, the researchers tested the drug in 52 patients with cancers that were PD-L1-positive as the first-line treatment. They found that:
  • The tumors shrank by more than 30 percent in 23% patients
  • The cancer stabilized in 17% patients
  • Severe side effects were experienced by 8% patients, which included back pain, fatigue, low blood sodium levels, low blood pressure, and migraine
The common side effects experienced by patients in both groups were fatigue and nausea.

More research in a larger group of patients is needed before the medication can be approved for use in triple negative metastatic breast cancer.

Reference:
  1. Adams S. Phase 2 study of pembrolizumab as first-line therapy for PD-L1-positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B. J Clin Oncol 35, (2017) (suppl; abstr 1088)
  2. Adams S. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol 35, (2017) (suppl; abstr 1008)


Source: Medindia

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