HER2-targeted therapies, originally developed for breast cancer, may also benefit patients with rare bile duct cancer and HER2-mutated breast cancer.

Drugs aimed at HER2-positive breast cancer may also help certain patients with bile duct cancer, as indicated by findings from a patient trial that will be presented at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. Bile duct cancer is uncommon, with few treatment options and low survival rates.
The trial also indicates that a broader category of breast cancer patients—specifically, those with HER2-mutated breast cancer—may benefit from these treatments.

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Combination Treatment Approach

In the trial, researchers used a combination of tucatinib and trastuzumab to treat patients with a variety of different tumors, all of which had signs of changes to a protein called human epidermal growth factor receptor 2 (HER2).

The research was presented by Dr. Yoshiaki Nakamura from the National Cancer Center Hospital East, Kashiwa, Japan.

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Trial Design and Treatment Regimen

The phase II trial included 217 patients from Europe, the USA, Japan, and South Korea with various types of tumors that either had unusually high levels of HER2 expression or alterations in HER2. Despite previous treatment, all the patients had tumors that had spread within the body (metastatic cancer).

Patients in the trial received 21-day cycles of tucatinib tablets twice every day and trastuzumab intravenously once every three weeks. Tucatinib and trastuzumab are drugs that have been designed to stop cancer cells from growing by targeting HER2. Because these treatments specifically target cancer cells, they can have fewer side effects than traditional chemotherapy.

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Trial Response Rates

Overall, patients in the trial had a 22.2% objective response rate (ORR). This is the proportion of patients whose cancer shrank. However, among the 30 patients with bile duct cancer who were taking part in the trial, the ORR was 46.7%.

Approved Combination Therapy for HER2-Positive Breast Cancer

A combination of tucatinib, trastuzumab and chemotherapy drug capecitabine is already approved for patients who have metastatic breast cancer with high levels of HER2 expression (known as HER2-positive). In the new trial of tucatinib and trastuzumab without capecitabine, for patients with metastatic breast cancer with alterations in HER2 (known as HER2-mutated), the ORR was 41.9% (31 patients).

Side effects experienced by patients included diarrhea, nausea, and anemia.

Dr. Nakamura said: “This chemotherapy-free combination was shown to be safe and well-tolerated. Very few patients had to stop treatment due to side effects.”

Variable Effects Across Different Types of Cancer

“The results of the study show variable effects across different tumor types. However, patients with HER2-positive metastatic bile duct cancer and HER2-mutated metastatic breast cancer experienced clinically relevant overall response rates.”

“These results support inclusion of this drug combination in guidelines for patients with previously treated HER2-postive bile duct cancer. The results for the patients with metastatic breast cancer suggest that those with HER2-mutated tumors could also benefit from these HER2-targeted treatments.”

Several other trials are testing tucatinib in combination with various different drug treatments, including in HER2-positive breast and bowel cancers.

Inclusivity of Rare Tumor Types

Dr. Tim Greten, senior investigator at the Center for Cancer Research, National Cancer Institute, USA, is co-chair of the EORTC-NCI-AACR Symposium and was not involved in the research. He said: “Cancer trials often focus on a particular type of tumor, such as breast or bowel cancer. This trial was designed to focus on the molecular makeup of the tumor, regardless of where it is in the body. This means that researchers can include rare forms of the disease, such as bile duct cancer, that urgently need more treatment options.”

Expanding HER2 Targeting Beyond Breast Cancer

“HER2 has been well-studied in breast cancer, but we are starting to see that it could be a useful target for treating other cancers. This study suggests that using two drugs that both target HER2 could prove beneficial for a wider group of breast cancer patients and for some patients with bile duct cancer. However, this is an early trial, and we need to see further research to confirm these results.”

Source-Eurekalert