Abstract GS1-01: Tucatinib vs placebo, both combined with capecitabine and trastuzumab, for patients with pretreated HER2-positive metastatic breast cancer with and without brain metastases (HER2CLIMB)

摘要: Objectives: The primary analysis from the HER2CLIMB study will describe efficacy and safety of tucatinib, trastuzumab, capecitabine, a treatment regimen under investigation for patients (pts) with advanced HER2+ metastatic breast cancer (BC) refractory to standard-of-care regimens. Rationale: Fifteen 20% pts diagnosed BC annually have overexpression or amplification HER2 receptor. While significant advances been made in BC, disease remains clinical challenge which no curative options are available. management CNS metastases (which occur at any time during course 30-50% those BC) an area unmet need. Tucatinib is investigational, oral tyrosine kinase inhibitor (TKI) that highly specific minimal inhibition EGFR In Phase 1b study, tucatinib plus capecitabine trastuzumab showed acceptable toxicity profile encouraging anti-tumour activity, including active brain metastases. Methodology: this double-blind, international, multicenter (NCT02614794), 612 locally previously treated pertuzumab, T-DM1 were randomized 2:1 receive (300 mg BID) placebo, combination (1000 mg/m2 BID, Days 1–14 each 21-day cycle) (6 mg/kg once every 21 days). Pts newly diagnosed, progressing, stable not requiring immediate local therapy included. endpoint PFS per RECIST 1.1 by blinded independent central review first 480 enrolled. Secondary endpoints, OS, be evaluated all pts. key secondary endpoints compared between arms using stratified log rank test; hazard ratio Cox regression model also reported. Anticipated Results: Baseline demographics characteristics presented arms. PFS, response rates, duration receiving vs placebo reported Common AEs SAEs both objectives, may if data sufficiently mature. Citation Format: Rashmi Murthy, Sherene Loi, Alicia Okines, Elisavet Paplomata, Erika Hamilton, Sara Hurvitz, Nancy Lin, Virginia Borges, Vandana Gupta Abramson, Carey Anders, Philippe L Bedard, Mafalda Oliveira, Erik Jakobsen, Thomas Bachelot, Shlomit S Shachar, Volkmar Mueller, Sofia Braga, Francois P Duhoux, Richard Greil, David Cameron, Lisa Carey, Giuseppe Curigliano, Karen Gelmon, Gabriel Hortobagyi, Ian Krop, Sibylle Loibl, Mark Pegram, Dennis Slamon, Maria Corinna Palanca-Wessels, Luke Walker, Wentao Feng, Eric Winer. combined pretreated HER2-positive without (HER2CLIMB) [abstract]. In: Proceedings 2019 San Antonio Breast Cancer Symposium; Dec 10-14; Antonio, TX. Philadelphia (PA): AACR; Res 2020;80(4 Suppl):Abstract nr GS1-01.