What is the recommended dosing regimen for Enhertu (trastuzumab deruxtecan)?

From the Guidelines

The recommended dosing regimen for Enhertu (trastuzumab deruxtecan) is 5.4 mg/kg administered as an intravenous infusion once every three weeks (21-day cycle) until disease progression or unacceptable toxicity occurs. This dosing regimen is based on the most recent and highest quality study available, which showed that the 5.4 mg/kg dose had a manageable safety profile and favorable efficacy outcomes, including an overall response rate (ORR) of 26.5% and a median progression-free survival (PFS) of 5.7 months 1.

Key Considerations for Dosing

• The dose should be administered as an intravenous infusion over 90 minutes for the first infusion, and if well-tolerated, subsequent infusions can be administered over 30 minutes.
• Dose modifications may be necessary based on individual patient tolerance, with potential dose reductions to 4.4 mg/kg and then to 3.2 mg/kg if needed for adverse reactions.
• Patients should be premedicated with antiemetics prior to each dose according to local institutional guidelines to manage nausea and vomiting.

Monitoring and Safety

• Regular monitoring for side effects is essential, particularly for interstitial lung disease/pneumonitis, neutropenia, and cardiac dysfunction, as these were among the most common treatment-emergent adverse events (AEs) of grade 3 or worse observed in the study 1.
• The safety profile of trastuzumab deruxtecan was generally manageable, but it is crucial to closely monitor patients for any signs of toxicity and adjust the dose accordingly.

Mechanism of Action

• Enhertu is an antibody-drug conjugate that combines the HER2-targeting properties of trastuzumab with a cytotoxic payload (deruxtecan), allowing for targeted delivery of chemotherapy to HER2-expressing cancer cells while minimizing systemic toxicity. This mechanism of action supports its use in patients with HER2-expressing tumors, regardless of the presence of stable CNS metastases at baseline or previous anti–PD-1 and anti–PD-L1 therapy 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION ... The recommended dosage of ENHERTU for HER2-positive, HER2-low, or HER2-ultralow breast cancer, HER2-mutant NSCLC, and HER2-positive (IHC 3+) solid tumors is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. ... The recommended dosage of ENHERTU for HER2-positive gastric cancer is 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

The recommended dosing regimen for Enhertu (trastuzumab deruxtecan) is:

• 5.4 mg/kg every 3 weeks for HER2-positive, HER2-low, or HER2-ultralow breast cancer, HER2-mutant NSCLC, and HER2-positive (IHC 3+) solid tumors
• 6.4 mg/kg every 3 weeks for HER2-positive gastric cancer Dosing is given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity 2

From the Research

Dosing Regimen for Enhertu (Trastuzumab Deruxtecan)

• The recommended dosing regimen for Enhertu (trastuzumab deruxtecan) is not explicitly stated in the provided studies, but the studies suggest that it is administered intravenously once every 3 weeks 3, 4, 5, 6.
• The dose of trastuzumab deruxtecan used in the studies varied, with doses ranging from 0.8 to 8.0 mg/kg 5.
• In the phase 1 dose-escalation study, the maximum tolerated dose of trastuzumab deruxtecan was not reached, and the recommended phase 2 dosing was 5.4 or 6.4 mg/kg 5.
• In the DESTINY-Lung01 study, patients received trastuzumab deruxtecan 5.4 mg/kg or 6.4 mg/kg intravenously once every 3 weeks 6.
• In the study of trastuzumab deruxtecan in recurrent uterine serous carcinoma, the patient received 5.4 mg/kg T-DXd without issue 7.

Administration and Safety

• Trastuzumab deruxtecan is administered intravenously once every 3 weeks 3, 4, 5, 6.
• Common treatment-related adverse events included haematological and gastrointestinal disorders 3.
• Interstitial lung disease (ILD)/pneumonitis is associated with a regulatory warning and requires careful monitoring 3, 6.