Rapid Readout: Assessment of Tucatinib vs Placebo in the HER2CLIMB Study of Pretreated Patients with HER2+ Metastatic Breast Cancer

Giuseppe Curigliano, MD, PhD, discusses data from the following study:

• 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). (Curigliano, Journal of Clinical Oncology, Abstract 1043)
  • The objective of this study is to report results in patients with pretreated HER2+ metastatic breast cancer with and without brain metastases treated with tucatinib vs placebo added to trastuzumab and capecitabine.
  • Tucatinib is an oral tyrosine kinase inhibitor (TKI) highly specific for HER2.
  • 612 patients were randomized 2:1 to receive tucatinib 300 mg twice a day or placebo, each in combination with trastuzumab and capecitabine.
  • Efficacy outcomes were assessed in the population for each agent:
    • Progression-free survival (PFS) assessed by blinded independent central review based on RECIST 1.1.
    • Overall survival (OS) and safety and tolerability of the regimens assessed.
  • Conclusions:
    • Overall survival benefit with tucatinib was maintained with an additional 15.6 months of follow-up (29.6 months total), with a 5.5-month improvement in median OS in the total population.
      • Overall survival benefit also maintained across all prespecified subgroups.
    • Improvement in overall survival observed in patients with and without visceral metastases was clinically meaningful.
    • Progression-free survival benefit based on investigator assessment was consistent with the primary analysis.
    • Tucatinib in combination with trastuzumab and capecitabine was well tolerated with a low rate of discontinuation due to adverse events.
      • Discontinuations due to adverse events were infrequent in both arms.
      • Rates of liver lab abnormalities and diarrhea remained stable with longer follow-up.
      • Safety profile was consistent with the primary analysis.