Seagen UK Ltd. today announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation in Great Britain 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.
The European centralised marketing authorisation granted by the European Commission for tucatinib is valid in Northern Ireland.
MHRA had previously granted tucatinib a Promising Innovative Medicine (PIM) designation. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.
“Every year, an estimated 55,000 people are diagnosed with breast cancer in the UK, of which up to one in five are estimated to have HER2-positive tumours,” said Dr. Alicia Okines, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust.
“The authorisation of tucatinib in combination with trastuzumab and capecitabine is a significant step forward for adult patients with advanced, incurable HER2-positive breast cancer.
With this authorisation, our patients, including those with disease that has spread to the brain, may have a new alternative therapeutic option that offers a meaningful survival benefit with a generally manageable side effect profile.”
“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 authorised in the UK, and we look forward to further collaborating with the national reimbursement bodies to ensure it is available to adult patients.”
The authorisation is based on results from the pivotal trial HER2CLIMB, 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 ado-trastuzumab emtansine (T-DM1).
HER2CLIMB Efficacy and Safety
The results for the primary endpoint showed patients who received tucatinib in combination with trastuzumab and capecitabine had a 46 percent reduction in the risk of cancer progression or death (progression free survival (PFS)) compared to patients who received trastuzumab and capecitabine alone, with a median PFS of 7.8 months vs. 5.6 months respectively (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001).
A secondary endpoint showed that the addition of TUKYSA reduced the risk of death (overall survival (OS)) by 34 percent (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048), with a median OS of 21.9 months (95% CI: 18.3 to 31.0) vs. 17.4 months (95% CI: 13.6 to 19.9).
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.
About HER2-Positive Breast Cancer
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. Historically, 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.
Tucatinib is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein.
In vitro (in lab studies), tucatinib inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signalling and cell growth (proliferation), and showed anti-tumour activity in HER2-expressing tumour cells.
In vivo (in living organisms), tucatinib inhibited the growth of HER2-expressing tumours.
The combination of tucatinib and the anti-HER2 antibody trastuzumab showed increased anti-tumour activity in vitro and in vivo compared to either medicine alone.