Trastuzumab-Deruxtecan (T-DXd; DS-8201) vs trastuzumab emtansine (T-DM1) in high-risk patients with HER2-positive, residual invasive early breast cancer (BC) after neoadjuvant therapy (NAT): a randomized, phase 3 trial (DESTINY-Breast05)

Background Patients with residual invasive disease after NAT are at greater risk for disease recurrence or death than those with a pathological complete response. The antibody-drug conjugate (ADC) T-DM1 was recently approved as postneoadjuvant treatment for patients with residual invasive disease (in breast and/or axillary nodes) after NAT and anti-HER2-treatment. T-DXd is a potent HER2-targeted ADC that was recently approved following phase 2 evidence (Modi NEJM 2020) for the treatment of patients with HER2-positive, unresectable/metastatic BC with ≥2 prior anti-HER2─based regimens (US) or prior chemotherapy and being refractory to or intolerant of standard treatments (Japan).

Methods DESTINY-Breast05 is a multicenter, open-label, randomized, phase 3 trial comparing efficacy and safety of T-DXd with T-DM1 in patients with HER2-positive (IHC 3+ or ISH+, centrally confirmed on pretreatment biopsy), invasive BC with residual invasive disease (breast and/or axillary lymph nodes) at presentation after NAT. Patients are eligible with either inoperable (cT4, N0-3, M0 or cT1-3, N2-3, M0) or operable BC (cT1-3, N0-1, M0) with axillary node-positive disease after NAT and anti-HER2-treatment. Approximately 1600 patients from 400 sites globally will be randomized (1:1) to T-DXd (5.4mg/kg) or T-DM1 (3.6mg/kg) intravenously once every 3 weeks for 14 cycles, stratified by operative status, hormone-receptor status, pathological nodal status, and anti-HER2-therapy. Primary endpoint is invasive disease-free survival, key secondary endpoint is disease-free survival. Other secondary endpoints are overall survival, distant recurrence-free interval, brain metastasis-free interval, safety. Pharmacokinetics of T-DXd, biomarkers, and health-related quality of life will be evaluated. Study start in Germany is planned for April 2021.

Publication History

Article published online:
01 June 2021