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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.
Ball-and-stick model from PubChem 2D record (no 3D conformer available). PubChem record
Trastuzumab backbone; DXd released by lysosomal cathepsins; TOP1 inhibition and bystander diffusion. Connects to HER2.
1.Antibody binds HER2 on the tumour cell surface
Source: US prescribing information (DailyMed). Doses are for orientation; the current label governs.
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.
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.
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.
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.
| Date | Deal | Type | Upfront | Total | Source |
|---|---|---|---|---|---|
| 2019-03-28 | Daiichi Sankyo to AstraZeneca Trastuzumab deruxtecan (DS-8201, Enhertu) | Co-development | $1.35bn | up to $6.9bn | source |
Breakthrough Therapy designation, HER2+ breast cancer source
Adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting
Accelerated approval, HER2+ metastatic breast cancer after ≥2 anti-HER2 regimens (DESTINY-Breast01) source
HER2+ gastric/GEJ adenocarcinoma (DESTINY-Gastric01) source
Adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting
Second-line HER2+ metastatic breast cancer (DESTINY-Breast03) source
HER2-low metastatic breast cancer (DESTINY-Breast04); first HER2-low indication source
Adult patients with unresectable or metastatic NSCLC whose tumors have an activating HER2 (ERBB2) mutation, as detected by an FDA-approved test, and who have received a prior systemic therapy
HER2-mutant NSCLC (accelerated) The confirmatory requirement was still open 4.1 years later, when the FDA's table was read. source
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.
HER2 IHC3+ solid tumours, tumour-agnostic (accelerated) The confirmatory requirement was still open 2.5 years later, when the FDA's table was read. source
HER2-low and HER2-ultralow HR+ breast cancer after endocrine therapy (DESTINY-Breast06) source
Early-stage HER2+ breast cancer: neoadjuvant (DESTINY-Breast11) and post-neoadjuvant residual disease (DESTINY-Breast05) source
| 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) |
| EU | 2023 | Unresectable or metastatic HER2-low breast cancer after chemotherapy in the metastatic setting or recurrence within 6 months of adjuvant chemotherapy (DESTINY-Breast04), hormone-receptor-negative disease included · https://www.ema.europa.eu/en/medicines/human/EPAR/enhertu |
| UK | 2024 | HER2-low metastatic or unresectable breast cancer after chemotherapy: NICE TA992 (29 July 2024) does not recommend trastuzumab deruxtecan, the cost per quality-adjusted life year being above the range NICE accepts; a rapid review (GID-TA12551) is in development · https://www.nice.org.uk/guidance/ta992 |
| US | 2024 | Unresectable or metastatic HER2-positive (IHC 3+) solid tumours after previous systemic treatment, including colorectal cancer · Tumour-agnostic accelerated approval on 5 April 2024; the colorectal evidence is DESTINY-CRC01 and DESTINY-CRC02 at 5.4 mg/kg. No NICE recommendation for colorectal cancer at September 2026. |
| 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 | - | - |
| Drug-related interstitial lung disease or pneumonitis (adjudicated) DESTINY-Breast04; 0.8 percent grade 5 | 12.1% | - |
Rates read from source 1source 2. Blank cells mean the figure was not sourced, not that it is zero.
Read for the class this product belongs to (antibody-drug conjugates with a topoisomerase-i payload) unless the answer names the product. Population figures from the cohorts named, not a prediction for one person. Blank where no source gives a recovery figure.
| 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.
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The IHC 3+ subgroup result is why the tumour-agnostic label is written at 3+ and not 2+, and why a gallbladder cancer with a strong HER2 stain now has two on-label choices (zanidatamab, trastuzumab deruxtecan) after chemotherapy. Lung toxicity again ran higher than in breast cancer.
Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.
The cleanest split of HER2 alterations in gallbladder cancer into amplification and mutation, which matters because IHC and ISH only see the amplified tumours. It also shows the high-incidence Chilean population has not been sequenced at scale.
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.
HER2 immunohistochemistry is now worth doing in advanced gynaecological and other cancers, since trastuzumab deruxtecan is approved for HER2 3+ solid tumours after prior therapy.
Together with the DESTINY-PanTumor02 biliary cohort this is the evidence behind trastuzumab deruxtecan's tumour-agnostic IHC 3+ label being used in gallbladder cancer; the lung toxicity rate, higher than in breast cancer, is the caution for a population with pre-existing lung and liver compromise.
Trastuzumab deruxtecan 5.4 mg/kg is the approved regimen for HER2-mutant lung cancer after platinum chemotherapy, and the trial is a rare example of dose optimisation improving safety without losing efficacy.
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.
Query 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.
Shares DESTINY-Lung01: trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer, DESTINY-Lung02: two doses of trastuzumab deruxtecan in HER2-mutant metastatic non-small-cell lung cancer, DESTINY-Gastric01: trastuzumab deruxtecan in previously treated HER2-positive gastric cancer, Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies.
Shares Noboru Yamamoto, Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies, Caution: DXd ADC + agents with pneumonitis risk, Living with an antibody-drug conjugate: diarrhoea, blood counts, eyes and lungs.
Shares Scalp Cooling in MBC, Testing Two Different Drugs (Sacituzumab-govitecan and Trastuzumab-deruxtecan) Combinations Prescribed in an Alterning Pattern to Patients With Metastatic or Lo, Living with an antibody-drug conjugate: diarrhoea, blood counts, eyes and lungs, Tumour-on-a-chip with blood flow to test whether big drugs actually get in.
Shares Ian E. Krop, Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People Wit, Protein-Matched ADC or PDC Umbrella Trial in Advanced Pancreatic and Breast Cancer, Sung-Bae Kim.
Shares Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status, Calibrated reference slides so every lab scores HER2-low the same way, HER2 IHC 1+, HER2 IHC 0 (HER2-negative, including ultralow).
Shares Zanidatamab zovodotin, Clinical and genomic characterization of ERBB2-altered gallbladder cancer: exploring differences between an American and a Chilean cohort, HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd, Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer.
Shares A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer, CNS penetration (brain-penetrant drugs), Brain metastases included by default in every solid-tumour trial, Systemic-first management of HER2-positive brain metastases.
Shares A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer, Can T-DXd alone cure early HER2-positive disease?, DESTINY-Breast09, Javier Cortés.