Trastuzumab deruxtecan gets FDA nod for HER2+ unresectable or metastatic breast cancer

  • US Food and Drug Administration

  • curated by Miriam Davis, PhD
  • Univadis Clinical Summaries
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Takeaway

  • The FDA has approved trastuzumab deruxtecan (fam-trastuzumab-deruxtecan-nxki, or ENHERTU) for patients with breast cancer with HER2+, unresectable and/or metastatic disease who failed ≥2 prior anti-HER2+ drug regimens.
  • This antibody-drug conjugate has high response rate (60.3%), but carries a boxed warning for interstitial lung disease (ILD).

Why this matters

  • Trastuzumab deruxtecan is an alternative to trastuzumab emtansine with more potent cytotoxicity.
  • A boxed warning requires monitoring for signs and symptoms of ILD, including cough and dyspnea.
  • If symptoms of ILD reach at least grade 2, the FDA says the antibody-drug conjugate should be permanently discontinued.
  • Prescribing information is available here.
  • The European Medicines Agency has not yet approved the antibody-drug conjugate.

Background

  • Recommended dose: 5.4 mg/kg by intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.
  • Efficacy and safety of trastuzumab deruxtecan were established in the DESTINY open-label trial:
    • 60.3% of 184 female patients (95% CI, 52.9%-67.4%) had an objective response rate:
      • 4.3% with complete response.
      • 56% with a partial response.
      • Median response duration: 14.8 (95% CI, 13.8-16.9) months.
    • ILD was reported in 9% of patients, 4 of whom died (2.6% of total patients).
  • The boxed warning also advises against receiving trastuzumab deruxtecan while pregnant because of embryo-fetal harm.