Trastuzumab deruxtecan
Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.
Approved in HER2+ metastatic breast cancer (DESTINY-Breast03: beat T-DM1), HER2-low (DESTINY-Breast04, 2022) and HER2-ultralow (DESTINY-Breast06, 2025) HR+ breast cancer, HER2+ gastric, HER2-mutant NSCLC, and tumour-agnostically for HER2 IHC 3+ solid tumours (2024). DESTINY-Breast09 (with pertuzumab) established it in first-line HER2+ metastatic disease. In Q2 2026 the FDA approved two early-stage HER2+ indications (neoadjuvant DESTINY-Breast11; post-neoadjuvant DESTINY-Breast05). Interstitial lung disease (~10-15%, ~1% fatal) requires monitoring. Membrane-permeable payload gives a strong bystander effect.
1.Antibody binds HER2 on the tumour cell surface
- Route
- IV infusion
- Schedule
- 5.4 mg/kg every 3 weeks (breast, NSCLC, HER2 IHC3+ tumours); 6.4 mg/kg every 3 weeks (gastric)
- Dose modifications
- Permanently discontinue for grade ≥2 ILD/pneumonitis; hold for grade 1 until resolved; reduce for neutropenia and LVEF decrease
- Monitoring
- Baseline and periodic LVEF; prompt CT and steroids for any respiratory symptoms; blood counts
Source: US prescribing information (DailyMed). Doses are for orientation; the current label governs.
- Medicare
- Part B (clinician-administered)
Given by infusion or injection in a clinic or hospital outpatient department, so it is a Part B drug: Medicare pays 80% after the Part B deductible and the patient owes 20% coinsurance, uncapped in Original Medicare unless a Medigap policy applies. HCPCS J9358.
- Commercial insurance
- covered with prior authorisation
Covered under the medical benefit with prior authorisation confirming diagnosis, biomarker status and line of therapy; site-of-care policies may steer infusions away from hospital outpatient departments. Plans require HER2 IHC/ISH results, including HER2-low documentation for the DESTINY-Breast04 indication.
- Assistance programmes
- ENHERTU4U (Daiichi Sankyo / AstraZeneca)
- AstraZeneca Access 360
- AZ&Me Prescription Savings
- PAN Foundation — Disease-specific co-pay and premium funds; open and closed funds change monthly.
- HealthWell Foundation
- CancerCare Co-Payment Assistance Foundation
- Patient Advocate Foundation Co-Pay Relief
20% Part B coinsurance on a high-cost infusion adds up quickly: Medigap Plan G or N, Medicare Advantage maximum out-of-pocket, Medicaid dual eligibility, or a charity fund are the usual buffers.
Sources: Medicare.gov: Chemotherapy · Medicare.gov: Prescription drugs (outpatient, Part B). Not medical or financial advice; verify with your plan.
- Appraised for
- HER2-positive unresectable or metastatic breast cancer after 2 or more anti-HER2 treatments
- Notes
- Second-line HER2-positive (DESTINY-Breast03) recommended in TA862 (2023). HER2-low breast cancer (DESTINY-Breast04) was not recommended in final guidance in 2024 after a dispute over the severity modifier, a decision widely criticised by patient groups; check NICE for any later resubmission. Gastric and NSCLC indications are separate appraisals.
- Cancer Drugs Fund
- Entered the Cancer Drugs Fund under a managed access agreement; check the current CDF list for whether it has since moved to routine commissioning.
- NHS England
- Routinely funded for the appraised indication (or via managed access)
Sources: NICE TA704 · NHS England Cancer Drugs Fund list · SMC advice: trastuzumab deruxtecan. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
- Aug 2017DesignationUS
Breakthrough Therapy designation, HER2+ breast cancer source
- 20 Dec 2019ApprovalUS
Accelerated approval, HER2+ metastatic breast cancer after ≥2 anti-HER2 regimens (DESTINY-Breast01) source
- 15 Jan 2021ApprovalUS
HER2+ gastric/GEJ adenocarcinoma (DESTINY-Gastric01) source
- 4 May 2022ApprovalUS
Second-line HER2+ metastatic breast cancer (DESTINY-Breast03) source
- 5 Aug 2022ApprovalUS
HER2-low metastatic breast cancer (DESTINY-Breast04); first HER2-low indication source
- 11 Aug 2022ApprovalUS
HER2-mutant NSCLC (accelerated) source
- 5 Apr 2024ApprovalUS
HER2 IHC3+ solid tumours, tumour-agnostic (accelerated) source
- 27 Jan 2025ApprovalUS
HER2-low and HER2-ultralow HR+ breast cancer after endocrine therapy (DESTINY-Breast06) source
- Q2 2026ApprovalUS
Early-stage HER2+ breast cancer: neoadjuvant (DESTINY-Breast11) and post-neoadjuvant residual disease (DESTINY-Breast05) source
Approvals
| Region | Year | Indication |
|---|---|---|
| US | 2019 | HER2+ metastatic breast cancer, ≥2 prior anti-HER2 regimens |
| US | 2022 | HER2-low metastatic breast cancer; HER2-mutant NSCLC |
| US | 2024 | HER2 IHC3+ solid tumours (tumour-agnostic) |
| US | 2025 | HER2-low/ultralow HR+ breast cancer after endocrine therapy (DESTINY-Breast06) |
| US | 2026 | Early-stage HER2+ breast cancer (neoadjuvant and post-neoadjuvant) |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Nausea DESTINY-Breast03/04; all-grade rates ≥20% per label | — | 7% |
| Fatigue DESTINY-Breast03/04; all-grade rates ≥20% per label | — | 6% |
| Neutropenia DESTINY-Breast03/04; all-grade rates ≥20% per label | — | 18% |
| Anaemia DESTINY-Breast03/04; all-grade rates ≥20% per label | — | 7% |
| Interstitial lung disease / pneumonitis 0.9% fatal; pooled breast studies at 5.4 mg/kg | 12% | — |
| Vomiting DESTINY-Breast03/04; all-grade rates ≥20% per label | — | — |
| Alopecia DESTINY-Breast03/04; all-grade rates ≥20% per label | — | — |
| Constipation DESTINY-Breast03/04; all-grade rates ≥20% per label | — | — |
| Decreased appetite DESTINY-Breast03/04; all-grade rates ≥20% per label | — | — |
Rates read from the US prescribing information. Blank cells mean the figure was not sourced, not that it is zero.
| Country | Reimbursement | List price | Assistance |
|---|---|---|---|
| United States | Medicare Part B (physician-administered); commercial plans per formulary | not disclosed | enhertu4u.com |
| United Kingdom | NICE: recommended in HER2+ breast cancer after ≥1 anti-HER2 regimen (TA862) and HER2-low breast cancer (TA1090); HER2-mutant NSCLC via CDF | not disclosed | — |
| Japan | NHI listed; approved in HER2+ breast and gastric cancer since 2020 | not disclosed | — |
List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.
Trials
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Landmark trials in OnCo
Patients with hormone-receptor-positive metastatic breast cancer that has stopped responding to endocrine therapy can be offered trastuzumab deruxtecan as their first chemotherapy-type treatment if the tumour shows any HER2 staining, rather than waiting until after conventional chemotherapy. Whether to use it before or after chemotherapy is now a choice, since overall survival was not shown to differ and the drug carries a risk of lung inflammation.
For HER2-positive metastatic breast cancer that has progressed after trastuzumab and a taxane, trastuzumab deruxtecan is now the standard second-line treatment and T-DM1 has moved later in the sequence. The benefit is large enough that ADC design, not just the target, is understood to be what matters. Patients need lung monitoring because of the risk of pneumonitis.
Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.
Latest papers
topQuery for this drug: (TITLE:"Trastuzumab deruxtecan" OR ABSTRACT:"Trastuzumab deruxtecan" OR TITLE:"Enhertu" OR ABSTRACT:"Enhertu" OR TITLE:"DS-8201" OR ABSTRACT:"DS-8201" OR TITLE:"T-DXd" OR ABSTRACT:"T-DXd") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Trastuzumab deruxtecan, not a curated reading list.
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