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Compared with physician’s choice treatment, trastuzumab deruxtecan shows a favorable benefit-risk profile in patients with HER2+ metastatic breast cancer
The randomized, open-label, multicentre phase 3 trial DESTINY-Breast02, recently published in The Lancet, by comparing efficacy and safety of trastuzumab deruxtecan with treatment of physician’s choice in HER2+ metastatic breast cancer patients shows that the antibody-drug conjugate has a favorable benefit-risk profile and can overcome resistance to a previous one.
The phase 3, DESTINY-Breast02 trial was designed to validate preliminary data reported in DESTINY-Breast01 and assess superiority of trastuzumab deruxtecan over treatment of physician’s choice in patients with HER2-positive metastatic breast cancer who previously received trastuzumab emtansine. DESTINY-Breast02 is complementary to DESTINY-Breast03, which first reported superiority of trastuzumab deruxtecan over trastuzumab emtansine in 2021, and it’s the first phase 3 trial investigating a HER2-directed agent after patients have received trastuzumab emtansine. The study involved 608 patients from 227 sites with an unresectable or HER2-positive metastatic breast cancer, who previously received trastuzumab emtansine. Patients were randomly assigned to receive trastuzumab deruxtecan or treatment of physician’s choice; the median follow-up was 21.5 months in the trastuzumab deruxtecan group and 18.6 months in the treatment of physician’s choice group. Median progression-free survival was 17.8 months in the trastuzumab deruxtecan group versus 6.9 months; grade 3 or higher treatment-emergent adverse events occurred 53% of patients receiving trastuzumab deruxtecan versus 44% receiving treatment of physician’s choice. As authors say, data show that «Trastuzumab deruxtecan is superior to conventional chemotherapy-based treatment options plus HER2-targeted agents in patients with HER2 positive metastatic breast cancer that is resistant or refractory to trastuzumab emtansine. We also showed the manageable safety of trastuzumab deruxtecan after two or more HER2-targeted regimens. The results of this trial support the clinical significance of using trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer and report for the first time in a randomized trial that an antibody-drug conjugate can overcome the resistance acquired to another antibody-drug conjugate. Trastuzumab deruxtecan has a superior benefit–risk ratio over conventional chemotherapy-based combinations with HER2-targeting agents. Further investigation on the real-world implication of using trastuzumab deruxtecan after trastuzumab emtansine and the optimal treatment sequencing of antibody-drug conjugates are warranted», authors conclude.