Advancement of trastuzumab deruxtecan in breast cancer treatment
Trastuzumab deruxtecan(T-DXd)is an antibody drug conjugate,which consists of trastuzumab,a linker and cytotoxic payload.T-DXd plays its effects relying on trastuzumab recognizing HER2-expressing tumor cells,and then enters the cells through endocytosis and pinocytosis;the linker is degraded by lysosome enzymes,releasing the payload topoisomerase I inhibitor exatecan derivative,thus imparts cytotoxic effect towards tumor cells.In the field of breast cancer treatment,for patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen,the PFS of T-DXd and trastuzumab emtansine was 28.8 months vs 6.8 months,respectively;for patients with unresectable or metastatic HER2-low breast cancer who have received a prior chemotherapy,the PFS of hormone receptor positive patients in T-DXd vs.treatment of physician's choice was 10.1 months vs 5.4 months,respectively.For breast cancer patients with brain metastasis,studies have shown that the intracranial lesion response rate of T-DXd was about 70％,with a median PFS of 14 months.Bone marrow suppression,liver function injuries,gastrointestinal reactions are common adverse reactions of T-DXd;interstitial lung disease/pneumonia is a special adverse reaction of T-DXd,which has a negative impact on the patients'quality of life and needs frequent monitoring,early detection and early treatment if happened.The ongoing T-DXd clinical researches cover the whole process of breast cancer treatment,mainly exploring its values in the first and second line therapy of advanced disease,as well as in the neoadjuvant and adjuvant stages for early breast cancer.This article reviews T-DXd's mechanism of action,pharmacodynamics and pharmacokinetics profiles,pivotal and ongoing clinical trials,and adverse reactions.
breast cancerantibody drug conjugatetrastuzumab deruxtecanexatecan derivatives
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