Tucatinib and Trastuzumab Combo as Maintenance Therapy for HER2+ Breast Cancer

The present first-line (1L) standard of care (SOC) for metastatic breast cancer (MBC) is human epidermal growth factor receptor 2-positive (HER2+) involves the administration of trastuzumab (T) and pertuzumab (P) along with a taxane. Despite the advancements in the first-line standard of care (SOC), most patients (pts) experience progression while undergoing maintenance therapy with T+P. Tucatinib, a tyrosine kinase inhibitor (TKI), has been authorized for use with T and capecitabine in adults with or without HER2+ MBC, with or without brain metastases (BM). The HER2CLIMB study demonstrated that the inclusion of tucatinib substantially extended the progression-free survival (PFS) and overall survival (OS) of patients diagnosed with HER2+ metastatic breast cancer (MBC) while being well-tolerated. Including tucatinib has decreased the likelihood of disease progression or mortality in patients with untreated and/or active brain metastases, as per Murthy et al. 2020 and Curigliano et al. 2021. The clinical trial HER2CLIMB-05 aims to evaluate the efficacy of tucatinib as an adjunct to first-line standard of care (SOC) in the maintenance therapy of patients, to prolong progression-free survival (PFS) without compromising their quality of life (QOL).

The HER2CLIMB-05 (NCT05132582) is a clinical trial in phase 3 that is randomized and double-blind. It aims to assess the effectiveness of tucatinib in combination with T+P as maintenance therapy for metastatic breast cancer that is HER2 positive. There will be an enrollment of approximately 650 patients. Patients who meet the criteria for eligibility will exhibit advanced HER2-positive disease, absence of progression following 4-8 cycles of the prior first-line standard of care, an ECOG Performance Status of 0 or 1, and either no brain metastases or asymptomatic brain metastases. The exclusion criteria comprise the previous administration of anti-HER2 and/or anti-epidermal growth factor receptor TKI (except prior SOC for early BC) and the incapability to undergo brain contrast magnetic resonance imaging. The patients will be randomly assigned in a 1:1 ratio to receive either tucatinib or placebo twice daily. The administration of Tucatinib and Placebo will be done once every 21 days. Patients diagnosed with hormone receptor-positive disease may be prescribed endocrine therapy. The principal objective is the investigator-evaluated progression-free survival (PFS). The secondary endpoints comprise overall survival (OS) as the primary endpoint, time taken for the decline in health-related quality of life, central nervous system progression-free survival (PFS), safety, and pharmacokinetic (PK) parameters. PFS and OS will be compared using a 2-sided stratified log-rank test between the treatment groups. The Kaplan-Meier method will be utilized to summarise time-to-event endpoints. The pharmacokinetic and safety information shall be summarised utilizing descriptive statistical methods. Enrollment is currently in progress within the United States, with plans for establishing further sites.

Source:https://meetings.asco.org/abstracts-presentations/213079

Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT05132582

Erika P. Hamilton, Ciara Catherine Maria O’Sullivan, Miguel Martin, Joohyuk Sohn, Konstantinos Tryfonidis, Libero Santarpia, Shan Yang, Veronique C Dieras/Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer (HER2CLIMB-05, trial in progress)/J Clin Oncol 40, 2022 (suppl 16; abstr TPS1108) DOI10.1200/JCO.2022.40.16_suppl.TPS1108