Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB).

Giuseppe Curigliano Istituto Europeo di Oncologia, Milan, IRCCS and University of Milano, Milan, Italy info_outline Giuseppe Curigliano, Volkmar Mueller, Virginia F. Borges, Erika P. Hamilton, Sara A. Hurvitz, Sherene Loi, Rashmi Krishna Murthy, Alicia Frances Clare Okines, Elisavet Paplomata, David A. Cameron, Lisa A. Carey, Karen A. Gelmon, Gabriel N. Hortobagyi, Ian E. Krop, Sibylle Loibl, Mark D. Pegram, Dennis J. Slamon, Jorge Ramos, Chiyu Zhang, Eric P. Winer

Authors Giuseppe Curigliano Istituto Europeo di Oncologia, Milan, IRCCS and University of Milano, Milan, Italy info_outline Giuseppe Curigliano, Volkmar Mueller, Virginia F. Borges, Erika P. Hamilton, Sara A. Hurvitz, Sherene Loi, Rashmi Krishna Murthy, Alicia Frances Clare Okines, Elisavet Paplomata, David A. Cameron, Lisa A. Carey, Karen A. Gelmon, Gabriel N. Hortobagyi, Ian E. Krop, Sibylle Loibl, Mark D. Pegram, Dennis J. Slamon, Jorge Ramos, Chiyu Zhang, Eric P. Winer Organizations Istituto Europeo di Oncologia, Milan, IRCCS and University of Milano, Milan, Italy, Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany, University of Colorado Hospital, Aurora, CO, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, MD Anderson Cancer Center, Houston, TX, The Royal Marsden NHS Foundation Trust, London, United Kingdom, Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, Edinburgh Cancer Research Centre, Edinburgh, United Kingdom, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, British Columbia Cancer - Vancouver Centre, Vancouver, BC, Canada, Dana-Farber Cancer Institute, Boston, MA, German Breast Group, Neu-Isenburg, Germany, Stanford Cancer Institute, Palo Alto, CA, University of California, Los Angeles/Jonsson Comprehensive Cancer Center, Los Angeles, CA, Seagen Inc., Bothell, WA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Seagen Inc Background: Tucatinib (TUC) is an oral tyrosine kinase inhibitor (TKI) highly specific for HER2. TUC is approved for use in combination with trastuzumab (T) and capecitabine (C) in patients (pts) with and without brain metastases (BM) who have received 1 or more prior anti-HER2–based regimens in the metastatic setting. In the primary analysis from the pivotal HER2CLIMB trial, the addition of TUC to T and C in pts with HER2+ metastatic breast cancer showed a statistically significant and clinically meaningful prolongation of progression-free (PFS) (HR = 0.54 [95% CI: 0.42, 0.71]; P < 0.001) and overall survival (OS) (HR = 0.66 [95% CI: 0.50, 0.88]; P = 0.005) (Murthy, et al. NEJM 2020). TUC in combination with T and C was well tolerated with few discontinuations other than for disease progression. Based on these data, the protocol was amended for unblinding of sites to treatment assignment to allow for crossover from the placebo arm to receive TUC in combination with T and C. Methods: HER2CLIMB (NCT02614794) is a global, randomized, double-blind, placebo-controlled trial in pts with unresectable locally advanced or metastatic HER2+ breast cancer previously treated with T, pertuzumab, and T-emtansine (T-DM1), including pts with untreated, treated stable, or treated and progressing BM. Overall 612 pts were randomized 2:1 to receive TUC 300 mg BID or placebo, each in combination with T and C. Randomization was stratified by BM, ECOG performance status, and geographic region. Protocol prespecified analysis of OS, PFS (by investigator assessment) and safety in the total study population will be performed at approximately 2 years from the last patient randomized. Results: Updated Kaplan-Meier time-to-event analysis of OS and PFS with hazard ratios and 95% confidence intervals for TUC arm vs placebo arm will be presented overall, as well as for OS in the prespecified subgroups reported previously (Murthy, et al. NEJM 2020). Safety and tolerability assessments will include frequency of adverse events by severity, dose modifications and discontinuation of study medications. Conclusions: Conclusions will be presented in the presentation. Clinical trial information: NCT02614794 .