It was announced today that the European Commission (EC) has granted marketing authorisation for tucatinib in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 treatment regimens.

Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.

“This approval is a significant advancement for patients in Europe, who will for the first time have an approved medicine demonstrating a survival benefit for HER2-positive metastatic breast cancer after disease progression following two standard anti-HER2 treatment regimens,” said Prof. Dr. Med Volkmar Mueller, Deputy Director at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany and investigator for the pivotal trial. “In the HER2CLIMB pivotal trial, the tucatinib combination regimen improved overall and progression-free survival compared to trastuzumab and capecitabine alone, including in patients with active, untreated or progressing brain metastases, a population with significant unmet need.”

“The tucatinib combination is a landmark therapy for patients with HER2-positive metastatic breast cancer with or without brain metastases, extending overall survival in these patients after two prior anti-HER2 treatment regimens,” said Clay Siegall, Ph.D., Chief Executive Officer at Seagen. “We are pleased tucatinib is now approved in Europe, and we look forward to further collaborating with individual countries to ensure it is available to patients.”

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion for tucatinib in December 2020.

The approval of tucatinib is valid in all countries of the European Union, as well as Norway, Liechtenstein, Iceland and Northern Ireland.

Patients who received tucatinib in combination with trastuzumab and capecitabine in the pivotal trial had a 46 percent reduction in the risk of cancer progression or death (PFS), the primary endpoint, compared to patients who received trastuzumab and capecitabine alone (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001) and improved overall survival with a reduction in the risk of death by 34 percent (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048).

The most common adverse reactions occurring in 20 percent or more of patients who received tucatinib were diarrhoea, nausea, vomiting, stomatitis, AST increase, ALT increase, and rash.

The pivotal trial, HER2CLIMB, is a randomised (2:1), double-blind, placebo-controlled, active comparator, global trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1 SmPC).

Patients with HER2-positive breast cancer have tumours with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells.

In 2020, more than two million new cases of breast cancer were diagnosed worldwide, including 531,086 in Europe. 

Between 15 and 20 percent of breast cancer cases are HER2-positive.

HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.

Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.

Source: Seagen