Tucatinib approval by EMA expands options for HER2-positive locally advanced or metastatic breast cancer

Abstract

On 10 December 2020, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for Tukysa (tucatinib) in combination with trastuzumab and capecitabine for the treatment of adult patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer (BC) who have received at least two prior anti-HER2 treatment regimens. The EMA’s recommendation is mainly based on the HER2CLIMB phase II trial, which randomized BC patients to receive trastuzumab and capecitabine with either tucatinib or placebo. Tucatinib demonstrated efficacy compared with placebo in terms of both progression-free survival (PFS) and overall survival (OS). A key unique feature of the HER2CLIMB trial was that, out of the w600 patients enrolled, 291 patients had brain metastases (BMs) at baseline. Furthermore, of these 291 patients, 60% had new or active BMs at study entry, defined as either new lesions or untreated lesions at baseline, or previously treated but progressing existing lesions. Of note, such patients have been traditionally excluded from enrollment in clinical trials. This is the first randomized trial in which an OS benefit for patients with BC and BMs was observed, which is an unmet medical need, especially in HER2-positive metastatic BC, where the occurrence of BMs is frequent, with at least half of patients developing BMs over the course of their disease. Until now, we had no drugs approved for the systemic treatment of BMs. In light of these clinical results, EMA’s announcement about tucatinib expands options for HER2-positive advanced BC (ABC).