ENCOURAGING RESEARCH RESULTS
Patients with metastatic breast cancer are living longer than ever, thanks to a new class of agents that target cell division to slow the progression of cancer when used with a hormonal treatment.
Breast cancer is considered metastatic when it originates in the breast and then moves to other organs such as the bones or liver.
“The goal of treatment is to try to control the disease,” said Dr. Patricia DeFusco, an oncologist and director of the Hartford HealthCare Cancer Institute Breast Program. “In the old days the survival rate used to be 18 months to two years. We are more successful now.”
Recent studies have shown an improvement in median survival for patients with metastatic breast cancer from 21 months to 38 months. Median survival in certain subsets of women with metastatic breast cancer now approaches five years, DeFusco said. From 2007 to 2016, the breast cancer death rate has decreased by 1.8 percent per year, according to American Cancer Society statistics.
One of these drugs has been studied in clinical trials at Hartford HealthCare in alliance with Memorial Sloan Kettering. Now that researchers know that hormonal treatments like letrozole combined with a targeted drug like palbociclib slow the progression of metastatic cancer, a next step is to see whether adding palbociclib to hormonal therapy in the post-operative setting can prevent metastases.
Women who have breast cancer tumors classified as hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative are at risk for late recurrence, sometimes 10 to 20 or more years after the first cancer. A study at the Hospital of Central Connecticut is examining whether there is any benefit to adding ribociclib to the standard treatment for patients with these types of breast cancer, DeFusco said.
“If it works in people with metastatic disease maybe it can help women if they are at high risk for a recurrence,” DeFusco said.
Three drugs, brand-named Ibrance (palbociclib), Kisquali (ribociclib) and Verzenio (abemaciclib), have been approved to treat metastatic breast cancer. They work by interfering with cell division and have been shown to be extremely effective in providing prolonged progression free-survival, DeFusco said.
These drugs are called cyclin-dependent kinase 4/6 inhibitors. CDK4 and CDK6 are enzymes used in cell division. Inhibiting these enzymes interrupts the growth of cancer cells. Adding a CDK4/6 inhibitor to endocrine therapy has been shown to increase survival in women vs. endocrine therapy alone, said Dr. Susanna Hong, a Middlesex Hospital oncologist.
However, the drugs are extremely expensive. Out of pocket, Ibrance costs $677 per capsule or $12,000 to $15,000 a month.
“Yes, financial toxicity is an issue,” DeFusco said.
All the drug companies have programs to help patients afford the drugs, and Hartford Hospital’s clinical pharmacists help the oncology team and the patient through the process of figuring out how to afford treatment. The team reviews a patient’s insurance to figure out how to minimize the cost to patient.
There can also be physical side-effects that need to be managed for CDK4/6 inhibitors, including drops in blood counts, increased risk of infection, fatigue and bone pain. But the drugs work and 70 percent of patients tolerate the drugs and reap the benefits, DeFusco said.
Treatment for metastatic breast cancer depends of the type of tumor, Hong said.
For example, patients with triple-negative breast cancer, the most aggressive type, can only be treated with chemotherapy at present.
However, a form of immunotherapy, called checkpoint inhibitors, is being investigated for breast cancer patients. A checkpoint inhibitor has recently been approved for use in women who have metastatic triple negative breast cancer that also has high expression of the PDL1 protein.
“Typically, we have cells called T-cells which attack viruses and foreign cells in our body,” Hong explained. “Cancer cells can attach to these cells via the PD-1 pathway, thus inactivating these cells. These medications prevent the cancer cells from inactivating the T-cells. This helps the T-cell see the cancer as foreign and attack it. At Middlesex, we are involved in a trial utilizing a type of immunotherapy after chemotherapy in women with triple negative breast cancer, with high expression of PDL1. The immunotherapy is given after surgery or in the adjuvant setting.”
Middlesex is also participating in a trial in which women who have had their cancer removed and have had it in the lymph nodes are given aspirin.
“Aspirin is an anti-inflammatory, and the goal is to determine if this can help prevent the cancer from returning,” Hong said.
Patients interested in participating in a clinical trial can check the website clinicaltrials.gov to see if there are any studies open for their particular type of disease.
Dr. Patricia DeFusco, left, is an oncologist and director of the Hartford HealthCare Cancer Institute Breast Program. Dr. Susanna Hong, at right, is a medical oncologist at Middlesex Hospital in Middletown.