FDA Expands Enhertu Approval for Treatment of ER+, HER2-low or HER2-ultralow Metastatic Breast Cancer

For patients with hormone receptor-positive metastatic breast cancer, treatment outcomes often decline after the disease progresses following endocrine-based therapy. A drug called trastuzumab deruxtecan (Enhertu) has demonstrated efficacy in treating metastatic breast cancer patients with low HER2 expression who have already undergone chemotherapy. Researchers recently evaluated trastuzumab deruxtecan earlier in the treatment process, specifically after endocrine-based therapy but before chemotherapy. 

In this phase 3, multicenter, open-label study, patients with hormone receptor-positive metastatic breast cancer with low or ultralow HER2 expression were randomized to receive either trastuzumab deruxtecan or physician’s choice of chemotherapy after one or more treatments with endocrine-based therapy.

The Study

• Researchers compared a new drug, trastuzumab deruxtecan, to standard chemotherapy.
• Participants had already tried hormone therapy but not chemotherapy for metastatic breast cancer.

Key Findings

1. Longer Time Without Cancer Progression
• Trastuzumab deruxtecan: 13.2 months
• Standard chemotherapy: 8.1 months
2. Effective for Both Low and Ultralow HER2 Levels
• The drug worked well for patients with very little HER2 protein on their cancer cells.
3. Side Effects
• More patients on trastuzumab deruxtecan experienced severe side effects (52.8%) compared to chemotherapy (44.4%).
• A lung condition called interstitial lung disease occurred more often in the trastuzumab deruxtecan arm.

Important Considerations

The study is still ongoing to determine if the treatment improves overall survival. Discuss with your doctor whether this treatment might be appropriate for you, considering its benefits and potential side effects. Enhertu is now FDA approved for the treatment of adult patients with unresectable or metastatic:

• HER2-positive breast cancer who have received a prior anti-HERs-based regiment in the metastatic setting or in the neoadjuvant/adjuvant setting in appropriate patients after recurrence. 

• HR-positive HER2-low or HER2-ultralow breast cancer as determined by an FDA-approved test that has progressed on one or more endocrine therapies in the metastatic setting
• HER2-low breast cancer as determined by an FDA-approved test who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of adjuvant chemotherapy.

Enhertu has a black box warning for interstitial lung disease and embryo-fetal toxicity. Enhertu is also FDA approved for appropriate patients with NSCLC, gastric or gastroesophagela junction cancer, and appropriate patients with HER2-positive solid tumors.

More Reading

Enhertu (Trastuzumab Deruxtecan) Treatment of HER2+ Breast Cancer

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Reference:

Bardia A, Hu X, Dent R, Yonemori K, et al; DESTINY-Breast06 Trial Investigators. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med. 2024 Sep 15.