Drug updated on 4/18/2024
| Dosage Form | Injection (intravenous; 100 mg/vial) |
| Drug Class | HER2-directed antibodies and topoisomerase inhibitor conjugates |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.
- Indicated for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) 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 completing adjuvant chemotherapy.
- Indicated for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.
- Indicated for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
- Indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.
Summary
- Fam-trastuzumab deruxtecan-nxki (Enhertu) is indicated for the treatment of adult patients with various types of unresectable or metastatic cancers, including HER2-positive breast cancer, HER2-low breast cancer, non-small cell lung cancer (NSCLC), gastric or gastroesophageal junction adenocarcinoma, and solid tumors. The drug has shown promising results in these indications.
- A total of 49 systematic reviews/meta-analyses were reviewed to gather information about Enhertu's efficacy and safety across its various indications. These studies compared Enhertu with other treatments such as trastuzumab-based regimens, lapatinib, tucatinib, and standard chemotherapies.
- In cases of HER2-positive metastatic breast cancer, especially after prior anti-HER2-based treatments have been used without success, Enhertu demonstrated superior efficacy when compared to trastuzumab emtansine (T-DM1) and other anti-HER2 therapies.
- For early-stage or locally advanced HER2-positive breast cancers treated in a neoadjuvant setting; while pyrotinib and lapatinib combined with trastuzumab showed high pathological complete response rates, the management of adverse events was challenging, particularly with pyrotinib use.
- When treating Non-Small Cell Lung Cancer (NSCLC), Enhertu displayed notable effectiveness, offering substantial progression-free survival benefits over existing therapies. It also proved useful in treating solid tumors where no satisfactory treatment options exist beyond those for breast cancer.
- In patients suffering from advanced HER2-positive gastric cancers who had previously undergone a trastuzumab-based regimen, the use of Enhertu resulted in effective outcomes similar to those seen within the metastatic breast cancer settings.
- The risk of cardiotoxicity associated with anthracycline & Trastuzumab treatments necessitates the use of protective strategies. The studies support Enhertu's favorable safety profile with manageable side effects in comparison to conventional therapies, although vigilance for interstitial lung disease/pneumonitis is advised.
- Enhertu's broad efficacy across different cancers and treatment lines signifies its role in addressing unmet medical needs, particularly in HER2-positive patients facing limited options. Its benefit extends to various subgroups including those with brain metastases and those who have rapidly progressed on previous therapies, suggesting a versatile role within cancer treatment protocols.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Enhertu (fam-trastuzumab deruxtecan-nxki) Prescribing Information. | 2024 | Daiichi Sankyo Inc., Basking Ridge, NJ |
Systematic Reviews / Meta-Analyses
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-College of American Pathologists guideline update. | 2023 | Journal of Clinical Oncology |
| Systemic therapy for advanced human epidermal growth factor receptor 2-positive breast cancer: ASCO guideline update. | 2022 | Journal of Clinical Oncology |
| ESMO clinical practice guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. | 2021 | Annals of Oncology |
| Breast cancer. Version 3. 2020. | 2020 | National Comprehensive Cancer Network |
| Treating breast cancer. | 2020 | American Cancer Society |
| Congress of neurological surgeons systematic review and evidence-based guidelines on the role of emerging and investigational therapties for the treatment of adults with metastatic brain tumors. | 2019 | Neurosurgery |