HER2+ metastatic breast cancer: add-on tucatinib extends survival in HER2CLIMB

  • Murthy RK & al.
  • N Engl J Med
  • 11 Dec 2019

  • curated by Miriam Davis, PhD
  • Univadis Clinical Summaries
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Takeaway

  • A large, international, randomized controlled trial (RCT) known as HER2CLIMB finds that tucatinib in combination with trastuzumab and capecitabine prolongs PFS and OS vs placebo in patients with heavily pretreated HER2+ metastatic breast cancer (mBCa).

Why this matters

  • Tucatinib is an investigational oral tyrosine kinase inhibitor highly selective for the HER2 kinase domain.
  • This trial brings regulatory approval one step closer.

Study design

  • International, double-blind, placebo-controlled RCT of tucatinib in combination with trastuzumab and capecitabine (the tucatinib-combination group) or placebo in patients with HER2+ mBCa (n=612) previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine.
  • Primary outcome: PFS at 1 year among the first 480 participants undergoing randomization.
  • Funding: Seattle Genetics.

Key results

  • PFS at 1 year:
    • The tucatinib-combination group had 46% greater PFS (33.1% vs 12.3% among placebo; HR, 0.54; 95% CI, 0.42-0.71) and longer median duration of PFS (7.8 vs 5.6 months, respectively).
    • In the subgroup with brain metastases, the tucatinib-combination group had 52% longer PFS (24.9% vs 0% among placebo; HR, 0.48; 95% CI, 0.34-0.69).
  • OS at 2 years:
    • The tucatinib-combination group had 34% greater OS (44.9% vs 26.6% among placebo; HR, 0.66; 95% CI, 0.50-0.88).
  • Safety:
    • The tucatinib-combination group had higher rates of grade ≥3 diarrhea and elevated aminotransferase levels.

Limitations

  • None identified by authors.