Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen
after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown
efficacy in patients with metastatic breast cancer with low expression of human epidermal
growth factor receptor 2 (HER2) after previous chemotherapy.We conducted a phase 3,
multicenter, open-label trial involving patients with hormone receptor-positive metastatic
breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical
[IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression
(IHC 0 with membrane staining) who had received one or more lines of endocrine-based
therapy and no previous chemotherapy for metastatic breast cancer. Patients were randomly
assigned in a 1:1 ratio to receive trastuzumab deruxtecan or the physician's choice
of chemotherapy. The primary end point was progression-free survival (according to
blinded independent central review) among the patients with HER2-low disease. Secondary
end points included progression-free survival among all the patients who had undergone
randomization, overall survival, and safety.Of the 866 patients who underwent randomization,
713 had HER2-low disease, and 153 had HER2-ultralow disease. Among the patients with
HER2-low disease, the median progression-free survival was 13.2 months (95% confidence
interval [CI], 11.4 to 15.2) in the trastuzumab deruxtecan group and 8.1 months (95%
CI, 7.0 to 9.0) in the chemotherapy group (hazard ratio for disease progression or
death, 0.62; 95% CI, 0.52 to 0.75; P<0.001); the results were consistent in the exploratory
HER2-ultralow population. Data for overall survival were immature. Adverse events
of grade 3 or higher occurred in 52.8% of the patients in the trastuzumab deruxtecan
group and in 44.4% of those in the chemotherapy group. Adjudicated interstitial lung
disease or pneumonitis occurred in 49 patients (11.3%; three events were grade 5 in
severity) and in 1 patient (0.2%; grade 2), respectively.Among patients with hormone
receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer who had received
one or more lines of endocrine-based therapy, treatment with trastuzumab deruxtecan
resulted in longer progression-free survival than chemotherapy. No new safety signals
were identified. (Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast06 ClinicalTrials.gov
number, NCT04494425.).
