Should the dose of Enhertu (trastuzumab deruxtecan) be reduced for the first cycle in patients with breast cancer?

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Last updated: June 23, 2025View editorial policy

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From the FDA Drug Label

The recommended dosage of ENHERTU is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. The dose of Enhertu (trastuzumab deruxtecan) should not be reduced for the first cycle in patients with breast cancer, as the recommended dosage is 5.4 mg/kg.

  • Dose reduction is recommended in cases of adverse reactions, as described in Table 1, but not for the first cycle. 1

From the Research

No, the dose of Enhertu (trastuzumab deruxtecan) should not be reduced for the first cycle in patients with breast cancer unless specific patient factors warrant a dose modification. The standard recommended dose of Enhertu for breast cancer is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity, as supported by the most recent study 2. Starting with the full dose allows for optimal efficacy of this antibody-drug conjugate, which combines the HER2-targeting properties of trastuzumab with a potent topoisomerase I inhibitor payload. Dose reductions should only be considered in response to specific adverse events that occur during treatment, such as neutropenia, interstitial lung disease, or left ventricular dysfunction, as noted in the study 3. If dose reductions become necessary during treatment, the first reduction is typically to 4.4 mg/kg and the second to 3.2 mg/kg. Patients should be monitored closely during therapy for potential side effects, with particular attention to pulmonary symptoms, cardiac function, and hematologic parameters, as highlighted in the study 4. Premedication for infusion-related reactions may be considered, but this does not require altering the actual dose of the medication. Key points to consider include:

  • The efficacy and safety of trastuzumab deruxtecan have been demonstrated in clinical trials, including the DESTINY-Breast01 study 2
  • Real-world outcomes have also shown the effectiveness of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer, as reported in the DE-REAL study 5
  • The FDA has approved trastuzumab deruxtecan for the treatment of unresectable or metastatic HER2-positive breast cancer, with a recommended dose of 5.4 mg/kg every 3 weeks 3
  • Close monitoring of patients during treatment is crucial to manage potential side effects and adjust the dose as needed, as emphasized in the study 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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