Trastuzumab deruxtecan has been added to the Pharmaceutical Benefits Scheme (PBS) for the treatment of metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer. Around 15-20% of all breast cancers are HER2 positive, with this subtype traditionally associated with poorer patient outcomes.
Trastuzumab deruxtecan is an antibody-drug conjugate (ADC). The antibody portion selectively targets the extracellular domain of the HER2 protein, and deruxtecan is a topoisomerase inhibitor. Once the ADC binds to HER2 on the tumour cell, it is internalised and undergoes enzymatic cleavage. This causes the topoisomerase I inhibitor to be released, which leads to DNA damage and apoptosis. The cytotoxic portion of the ADC has high membrane permeability, allowing it to also act against neighbouring cells. This “bystander effect” is beneficial as not all cells in HER2-positive breast cancer overproduce HER2.
Trastuzumab deruxtecan is not interchangeable with trastuzumab (Herzuma®) or trastuzumab emtansine (Kadcyla®). The DESTINY-Breast03 trial compared the efficacy and safety of trastuzumab deruxtecan with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. In the trastuzumab deruxtecan group, 75.8% of patients were alive without disease progression at 12 months, compared to 34.1% in the trastuzumab emtansine group. The overall incidence of drug-related adverse effects was higher in the trastuzumab deruxtecan group (98.1% versus 86.6%). The incidence of interstitial lung disease was also higher in the trastuzumab deruxtecan group (10.5%) compared to the trastuzumab emtansine group (1.9%). Patients should be monitored for signs and symptoms of this condition and advised to immediately report cough, dyspnoea, fever, or new or worsening respiratory symptoms.
- Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022; 386: 1143-54.
- Enhurtu® (Trastuzumab deruxtecan) Australian approved product information. Macquarie Park: AstraZeneca. Approved January 2023.
- Exman P, Tolaney S. HER2-positive metastatic breast cancer: a comprehensive review. Clin Adv Hematol Oncol. 2021; 19(1): 40-50.
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