- 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.
- 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.
- 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).
- The tucatinib-combination group had higher rates of grade ≥3 diarrhea and elevated aminotransferase levels.
- None identified by authors.