HER2-postive breast cancer drugs show promise for bile duct cancer treatment

Drugs designed to target HER2-postive breast cancer could also benefit some patients with bile duct cancer, according to results of a patient trial to be presented on Thursday at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. Bile duct cancer is rare, treatment options are limited, and the survival rates are low.

The trial also suggests that a wider group of breast cancer patients – those with HER2-mutated breast cancer – could be treated with these drugs.

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.

The phase II trial included 217 patients from Europe, the USA, Japan and South Korea with various different 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 on 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.

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%.

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 diarrhoea, nausea and anaemia.

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.

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."

Dr. Yoshiaki Nakamura, National Cancer Center Hospital East, Kashiwa, Japan

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

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 make-up 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.

"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."