A promising new line of treatment has emerged for HER2-positive breast cancer

A recent clinical trial carried out across 15 different countries reported an unprecedented successful outcome using the drug, Tucatinib, as a treatment option for HER2-positive metastatic breast cancer patients. Patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer make up approximately 20% of all breast cancers. HER2 is a protein that promotes the growth of cancer cells because it encourages cells to grow and divide quickly. Cancer is a disease where abnormal cells divide and grow unconditionally, and so you can imagine that people who have HER2-positive cancer and thus an abnormally large amount of the cancer-causing protein, will have a very aggressive form of cancer that can quickly become worse. 

HER2-positive breast cancer patients have an increased amount of the HER2 protein present, which causes the cancer cells to grow and divide much faster.

Despite significant therapeutic advances in the past twenty years, most HER2-positive breast cancer patients are unlikely to recover from their cancer and often ultimately die from their disease. As therapies have improved, the incidence of brain metastases, which is the invasion of cancer cells originating from the breast into the brain, has simultaneously increased. This invasion of cancer cells into the brain is occurring in up to half of all HER2-positive breast cancer patients. There are very limited treatment options for patients who relapse after standard therapy with multiple HER2-targeted agents; but for patients who relapse and also have brain metastases, the outlook is even worse.

Doctors and scientists from all over the US, Europe and Australia have collaborated on a 612-person clinical trial using Tucatinib as a treatment option for HER2-positive patients who have relapsed. Since high levels of the HER2 protein are promoting cancer cells to grow and spread, the Tucatinib drug was developed to limit the production of HER2 by the body. Tucatinib is a type of drug called a tyrosine kinase inhibitor, which means that it is able to identify and attach to the HER2 protein, blocking its function. Therefore, cancerous cells which have high levels of HER2 end up dying thanks to the action of this drug, while normal cells are often left to live. Normally, HER2-positive metastatic breast cancer patients will receive a first line of 3 drugs together over a year, and then if they still show evidence of cancer cells present, they take a second line of two drugs combined. However, if the second line of treatment is unsuccessful, there is no available standard of care. Often patients attempt a third line of chemotherapy or enroll in a clinical trial, hoping for the best, but usually expecting the worst.

In this recent clinical trial, all patients were at this stage where they had received previous drug combinations that were not successful in removing all cancer cells. The women were randomly divided into two groups: one group was given the investigational drug Tucatinib with other common chemotherapies; and the other group was given a placebo drug with the same chemotherapy combination. The results were exciting! The patients treated with Tucatinib lived 2 months longer without their cancer worsening than those in the placebo group. Additionally, after two years there was a 46% lower risk of the cancer worsening or death in women treated with Tucatinib than without. However, possibly the most encouraging results were witnessed in women whose cancer had spread to the brain, which accounted for 45% of the participants. Of the women with cancer now in the brain, 25% were still alive without their cancer worsening 1 year after treatment with Tucatinib, compared to 0% survival in the placebo group. Most patients did experience some negative side effects, but only 6% of the women stopped the drug due to discomfort.

The trial’s overall findings “are unprecedented for late-line therapy in advanced breast cancer,” said its lead investigator, Rashmi Murthy, M.D., of the University of Texas MD Anderson Cancer Center, in a press release. Many cancer biologists have remarked on the promising results of Tucatinib as a treatment option for HER2-positive metastatic breast cancer patients who usually face a dismal outlook. Specifically, women who have cancer spread to the brain should benefit significantly. Based on the positive results of this clinical trial, the FDA granted ‘Breakthrough Therapy Designation’ for the addition of Tucatinib to the other chemotherapy drugs for advanced HER2-positive metastatic breast cancer, including patients with brain metastases. This decision by the FDA recognizes the urgent need for new medicines that can improve the lives of those with this breast cancer. This year, Seattle Genetics hopes to work tirelessly to make this therapy available to patients as soon as possible.

Source:
Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W and Winer EP. 2019. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. doi: 10.1056/NEJMoa1914609. [Epub ahead of print]