What Is Trastuzumab Deruxtecan (Enhertu)? FDA Approval, Licensing and Reimbursement in Turkey
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What Is Trastuzumab Deruxtecan (Enhertu)?
Last updated: October 2026
Enhertu (trastuzumab deruxtecan) is an intravenous antibody-drug conjugate in which a powerful chemotherapy medicine is attached to an antibody that recognizes HER2. It is used in HER2-positive, HER2-low and ultralow breast cancer, HER2-positive gastric cancer, HER2-mutant lung cancer and other HER2-positive solid tumors. It is licensed in Turkey but is not reimbursed by SGK.
- Who receives it: In the United States, approved across a broad range of breast cancer settings, from first-line treatment (with pertuzumab) to preoperative and postoperative treatment; also for gastric, lung and other HER2-positive tumors.
- Evidence: In HER2-positive breast cancer, it increased the time without disease progression from 7.2 to 29.0 months versus trastuzumab emtansine in second-line treatment, and from 26.9 to 40.7 months with pertuzumab in first-line treatment.
- Most important risk: Lung inflammation (interstitial lung disease) occurs in approximately 12% of patients and is rarely life-threatening. Contact your treatment team the same day if you develop a new cough, shortness of breath or fever.
- Turkey: Licensed; a 100 mg vial costs 44538 TL. One cycle costs approximately 178 thousand TL for a patient weighing 70 kg. No SGK reimbursement.
Why Does This Matter?
Approximately one-fifth of breast cancers overexpress the HER2 protein, and these tumors have long been treated with HER2-targeted medicines such as trastuzumab. Enhertu changed this approach in two ways: it demonstrated clear superiority over previous standards in HER2-positive disease, and proved effective in tumors with low HER2 expression previously classified as "HER2-negative." This created a new treatment option for a substantial proportion of patients with metastatic breast cancer.
However, the medicine's serious lung toxicity can be life-threatening if not recognized early. Continuing treatment safely depends on vigilance from both the patient and the care team. Its licensing in Turkey without SGK reimbursement is also a striking example of the gap between evidence and access.
What Is Enhertu and How Does It Work?
Enhertu (trastuzumab deruxtecan) is an antibody-drug conjugate in which a topoisomerase I inhibitor chemotherapy medicine (DXd) is attached by a cleavable linker to the HER2-targeting antibody trastuzumab. The antibody delivers the medicine to HER2-expressing tumor cells; DXd released inside the cell causes DNA damage. It was developed by Daiichi Sankyo and AstraZeneca.
Two features distinguish Enhertu from similar medicines. First, approximately 8 drug molecules are attached to each antibody, about twice the ratio of the older HER2-targeted conjugate trastuzumab emtansine (T-DM1). Second, released DXd can cross cell membranes and affect nearby tumor cells with little or no HER2 expression (the bystander effect). These two features explain why the medicine also works in tumors with low HER2 levels.
Figure 1 · How Does Enhertu Work?
The four steps of the antibody-drug conjugate.
HER2 Levels and Enhertu's Role
| HER2 status | Pathology result | Enhertu use (United States) |
|---|---|---|
| HER2-positive | IHC 3+ or IHC 2+ and ISH-positive | From first-line treatment; before and after surgery |
| HER2-low | IHC 1+ or IHC 2+ and ISH-negative | After chemotherapy; after hormonal therapy in hormone-positive disease |
| HER2-ultralow | IHC 0, but weak membrane staining in some cells | After hormonal therapy in hormone-positive disease |
| HER2-zero | No staining | No approved use |
The distinction between HER2-low and ultralow can easily be missed in a pathology report. Reassessing earlier biopsies or obtaining a new biopsy is therefore important when planning treatment for metastatic breast cancer.
When and for Which Cancers Did Enhertu Receive FDA Approval?
The first European approval came in January 2021. In 2026, tumor-agnostic use (June) and first-line treatment with pertuzumab (September) were also approved, and a positive opinion was issued for postoperative use. DESTINY-Gastric04 results showing longer overall survival than ramucirumab-paclitaxel in gastric cancer are discussed in this article.
What Did Clinical Trials Show?
| Trial | Patient group | Main result |
|---|---|---|
| DESTINY-Breast09 | HER2-positive metastatic, first-line | With pertuzumab, a 44% lower progression risk than THP (HR 0.56); response rates of 85.1% versus 78.6%. Overall survival data are not yet mature. |
| DESTINY-Breast03 | HER2-positive metastatic, second-line | Overall survival of 52.6 versus 42.7 months compared with T-DM1 (HR 0.73) |
| DESTINY-Breast04 | HER2-low metastatic, after chemotherapy | Overall survival of 23.4 versus 16.8 months compared with chemotherapy (HR 0.64) |
| DESTINY-Breast06 | Hormone-positive, HER2-low/ultralow, before chemotherapy | Progression risk reduced by 38% in HER2-low disease (HR 0.62) and 22% in ultralow disease (HR 0.78) |
| DESTINY-Breast05 | Early HER2-positive disease, residual tumor after preoperative treatment | 3-year invasive disease-free survival of 92.4% versus 83.7% with T-DM1 (HR 0.47) |
| DESTINY-Breast11 | Stage II-III HER2-positive, preoperative | Pathological complete response of 67.3% versus 56.3% |
| DESTINY-Gastric01 and 04 | HER2-positive gastric cancer, second-line | In Gastric04, overall survival of 14.7 versus 11.4 months with ramucirumab-paclitaxel (HR 0.70) |
| DESTINY-Lung02 | HER2-mutant lung cancer | At 5.4 mg/kg, response rate of 49%; less lung inflammation than at 6.4 mg/kg |
| DESTINY-PanTumor02 | Various HER2 IHC 3+ solid tumors | Response rate of 61.3%; median overall survival of 21.1 months |
How Is Enhertu Administered?
| Use | Dose | Duration |
|---|---|---|
| Metastatic breast cancer, lung cancer and other solid tumors | 5.4 mg/kg every 3 weeks | Until progression or unacceptable side effects |
| Preoperative (early breast cancer) | 5.4 mg/kg every 3 weeks | 4 cycles, followed by THP |
| Postoperative (residual tumor) | 5.4 mg/kg every 3 weeks | Up to 14 cycles |
| Gastric cancer | 6.4 mg/kg every 3 weeks | Until progression or unacceptable side effects |
- Infusion: The first infusion is given over 90 minutes; if well tolerated, subsequent infusions are shortened to 30 minutes.
- Nausea prevention: Because nausea and vomiting are common, anti-nausea medicines are given before each cycle.
- Monitoring: A complete blood count and assessment of respiratory symptoms before each cycle; cardiac function (LVEF) assessed by echocardiography before treatment and at regular intervals; a pregnancy test before treatment in women who could become pregnant.
- Contraception: Women should use effective contraception for 7 months after the last dose, and men whose partners could become pregnant for 4 months.
What Are Enhertu's Side Effects?
According to the United States product information, the most common side effects (20% or more) are nausea, fatigue, vomiting, hair loss, constipation, loss of appetite, diarrhea and musculoskeletal pain. Blood tests commonly show reduced white blood cells, neutrophils, hemoglobin and platelets, increased liver enzymes and low potassium.
| Important side effect | Frequency (5.4 mg/kg) | What is done? |
|---|---|---|
| Lung inflammation (interstitial lung disease) | 12% (deaths 0.9%) | Interruption or permanent discontinuation depending on symptoms; corticosteroids |
| Low neutrophils | 65% (severe 19%) | Dose delay or reduction |
| Reduced heart function (LVEF) | 4.6% | Echocardiographic monitoring; discontinue in heart failure |
It carries a boxed warning in the product information. Median time to onset is approximately 5.5 months, but it can occur at any point during treatment. If you develop a new or worsening cough, shortness of breath or fever, contact your oncology team the same day, without waiting for the next cycle.
Figure 2 · Monitoring for Lung Inflammation
An action plan for interstitial lung disease during Enhertu treatment.
Enhertu in Turkey: Licensing, Price and SGK Status
- License: Licensed since May 2024; the marketing authorization holder is Daiichi Sankyo. Turkey's product information (SmPC) includes HER2-positive and HER2-low metastatic breast cancer, HER2-positive gastric cancer and HER2-mutant lung cancer. HER2-ultralow breast cancer, first-line combination with pertuzumab and early-stage uses are not yet included in the Turkish license.
- SGK: Not reimbursed for any indication ("cost not covered"). Patients obtain the medicine from a pharmacy at their own expense.
- Legal action: Some patients have filed cases in labor courts after SGK rejected coverage, and courts have ordered payment for the medicine through interim injunctions. Each case is assessed individually and a favorable outcome is not guaranteed; support should be sought from a lawyer specializing in health law.
| Date | Enhertu 100 mg retail price |
|---|---|
| August 2024 (first record) | 27160.06 TL |
| October 2024 | 33547.10 TL |
| December 2025 | 38753.26 TL |
| March 2026 (current) | 44538.10 TL |
Example cost: For a patient weighing 70 kg, a 5.4 mg/kg dose is 378 mg and requires 4 vials; one cycle costs approximately 178152 TL. With treatment every three weeks, approximately 17 cycles a year bring the annual medicine cost to more than 3 million TL.
Frequently Asked Questions
- Is Enhertu Chemotherapy?
- Enhertu is an antibody-drug conjugate: an antibody recognizing HER2 carries a powerful chemotherapy medicine to the tumor cell. It is therefore a targeted medicine, but chemotherapy-like side effects such as nausea, hair loss and reduced blood counts occur.
- Can Enhertu Be Used in HER2-Negative Breast Cancer?
- It can be used for tumors classified as HER2-low (IHC 1+ or 2+) or ultralow (IHC 0 but weak membrane staining) in the pathology report. It is not approved for tumors with no HER2 staining. Reassessment of the pathology report may be needed to make this distinction.
- Which Symptoms Mean I Should Call My Doctor Immediately While Taking Enhertu?
- A new or worsening cough, shortness of breath or fever may indicate lung inflammation; contact your team the same day. Fever with weakness and chills suggests an infection related to low neutrophils.
- Is Enhertu Covered by SGK?
- No, as of October 2026. Although Enhertu is licensed in Turkey, it is not on SGK's reimbursement list. Some patients have obtained interim injunctions through legal action; consulting a health law specialist is recommended.
Glossary
- Antibody-drug conjugate
- A powerful chemotherapy medicine attached to an antibody that recognizes a target on tumor cells; it delivers the medicine directly to the tumor.
- HER2-low / ultralow
- Low levels of HER2 in a tumor; it does not respond to conventional HER2-targeted medicines but may benefit from Enhertu.
- Interstitial lung disease
- Inflammation of lung tissue; Enhertu's most serious side effect.
DROZDOGAN Academy Commentary
Enhertu is one of the clearest examples of how rapidly antibody-drug conjugates can expand in oncology. In seven years, it progressed from third-line treatment to early breast cancer.
⚡ Why it matters
It moved HER2-targeted therapy beyond the "positive/negative" divide; HER2-low and ultralow tumors became a new treatment group.
✅ Current evidence
DESTINY-Breast03 prolonged overall survival versus T-DM1; DB-04 showed a survival benefit in HER2-low disease; DB-09 and DB-05 changed standards in first-line and early-stage treatment.
⚠️ Limitations
Lung inflammation is unpredictable and rarely life-threatening. Overall survival data from DB-09 are not yet mature. Turkey's licensed indications lag behind those in the United States, and SGK does not reimburse treatment.
🩺 What to Do in Practice
- Determine HER2 levels with an up-to-date, accurate test.
- At every cycle, assess respiratory symptoms.
- Before and during treatment, monitor cardiac function.
- Inform the patient early about cost and access.
❓ Open Questions
What is the best treatment after Enhertu? How does resistance develop? How will the definition of HER2-ultralow be standardized? When will reimbursement be available in Turkey?
Our Brief Verdict: Enhertu has strong supporting evidence and changes treatment standards in HER2-positive and HER2-low breast cancer. Early recognition of lung symptoms is the key to safe use.
- This article was prepared in October 2026. Indication, dose and side-effect information is based on the May 2026 United States product information; FDA dates on FDA announcements; trial results on FDA, ASCO Post, OncLive, Nature Medicine and company announcements; and Turkish information on the SmPC, medicine price databases and an article from a law firm.
- Not verified: The official source for Turkey's licensing date; the full wording of SmPC indications; and whether Enhertu was included in the June and August 2026 Healthcare Implementation Communiqué (SUT) amendments (it does not appear in the sources available for review).
- Based on general knowledge: The approximate proportion of all breast cancers that are HER2-positive and the calculation of annual treatment cycles.
- The diagrams and Academy commentary are our own. Information about legal proceedings is for general information, not legal advice. This article does not provide individual medical advice.
Sources
- FDA. ENHERTU (fam-trastuzumab deruxtecan-nxki) prescribing information, 05/2026. accessdata.fda.gov
- FDA. Initial approval, 20.12.2019. fda.gov
- FDA. Gastric cancer approval, 2021. fda.gov
- FDA. DESTINY-Breast03 full approval, 2022. fda.gov
- FDA. HER2-low breast cancer approval, 2022. fda.gov
- Accelerated approval for HER2-mutant lung cancer. ASCO Post, 2022. ascopost.com
- FDA. Tumor-agnostic approval, 2024. fda.gov
- HER2-low and ultralow approval. OncLive, 2025. onclive.com
- FDA approval of T-DXd plus pertuzumab. ASCO Post, December 2025. ascopost.com
- DESTINY-Breast09 results. ASCO Post, 2025. ascopost.com
- FDA. Two approvals in early HER2-positive breast cancer, 15.05.2026. fda.gov
- Hurvitz SA et al. DESTINY-Breast03 long-term survival. Nat Med. 2024. nature.com
- DESTINY-Gastric04, Daiichi Sankyo announcement, 2026. daiichisankyo.com
- DESTINY-Lung02 results. ASCO Post, 2023. ascopost.com
- Enhertu 100 mg SmPC (Turkey). daiichi-sankyo.com.tr
- Enhertu price history. ilacrehberi.com
- Enhertu SGK court cases. Minval Hukuk. minvalhukuk.com
Sources
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