- Adding tucatinib to trastuzumab and capecitabine in heavily treated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer reduced risk for disease progression and death.
- OS was 4.5 months longer with tucatinib vs placebo in phase 2 HER2CLIMB trial.
Why this matters
- 47% of patients in this trial had brain metastases, a population that has been historically excluded from clinical trials.
- Authors pointed out a reduction in disease progression and mortality risk is clinically meaningful.
- Data cutoff: September 4, 2019, with a median follow-up of 14 months.
- 1-year PFS (95% CIs):
- 33.1% (26.6%-39.7%) tucatinib vs 12.3% (6.0%-20.9%) placebo.
- Median duration: 7.8 (7.5-9.6) months with tucatinib vs 5.6 (4.2-7.1) months, placebo.
- Risk for disease progression/death decreased by 46% with tucatinib vs placebo:
- HR, 0.54 (0.42-0.71; P<.001>
- 2-year OS:
- 44.9% (36.6%-52.8%) tucatinib vs 26.6% (15.7%-38.7%) placebo; HR, 0.66 (P=.005).
- Median OS duration: 21.9 (18.3-31.0) months with tucatinib vs 17.4 (13.6-19.9) months, placebo.
- 1-year PFS among patients with brain metastases was significantly higher with tucatinib (24.9% vs 0%; HR, 0.48 [P<.001>
- Median PFS duration: 7.6 (6.2-9.5) months with tucatinib vs 5.4 (4.1-5.7) months, placebo.
- Grade ≥3 more common with tucatinib.
- AE-related discontinuation: 5.7% tucatinib vs 3.0% placebo.
- Multinational (155 sites, 15 countries), randomized, double-blind, controlled trial of tucatinib-combination (n=410) vs placebo-combination (n=202).
- Participants had previously treated locally advanced/metastatic HER2+ breast cancer with or without progressive brain metastases.
- Funding: Seattle Genetics.
- Specific to a clinical population with late disease.
- Report published simultaneously in the New England Journal of Medicine.