For US Healthcare Professionals
For US Healthcare Professionals
Neoadjuvant Safety Data
ENHERTU has serious Warnings and Precautions. Click here for information related to monitoring for and management of ILD/pneumonitis. Please click here for full Prescribing Information, including Boxed WARNINGS, and click here for Medication Guide.
With ENHERTU followed by THP in patients with HER2+ eBC in the neoadjuvant setting
The benefit-risk profile of ENHERTU–THP was demonstrated in DESTINY-Breast111,2
No new safety signals were identified in the ENHERTU–THP arm
See Important Safety Information below, which includes Warnings and Precautions and Boxed WARNINGS for ILD/pneumonitis and embryo-fetal toxicity. Click here for study results related to ILD/pneumonitis and information related to monitoring and management.
- Median duration of neoadjuvant treatment: 5.6 months (range: 0.7-9.1) with ENHERTU–THP1
| Clinically relevant AE considerations2 |
ENHERTU–THP (n=320) |
ddAC-THP (n=312) |
|---|---|---|
| Serious AEs | 10.6% | 20.2% |
| AE leading to discontinuation | 14.1% | 9.9% |
| AE leading to dose interruption | 37.8% | 54.5% |
| AE leading to dose reduction | 18.1% | 19.2% |
|
Clinically relevant AE considerations2 |
|
|---|---|
| Serious AEs | |
|
ENHERTU–THP (n=320) |
10.6% |
|
ddAC-THP (n=312) |
20.2% |
| AE leading to discontinuation | |
|
ENHERTU–THP (n=320) |
14.1% |
|
ddAC-THP (n=312) |
9.9% |
| AE leading to dose interruption | |
|
ENHERTU–THP (n=320) |
37.8% |
|
ddAC-THP (n=312) |
54.5% |
| AE leading to dose reduction | |
|
ENHERTU–THP (n=320) |
18.1% |
|
ddAC-THP (n=312) |
19.2% |
10.6% of patients experienced a serious AE with
ENHERTU–THP2
- 20.2% of patients in the ddAC-THP arm experienced a serious AE
97.2% of patients underwent surgery following treatment with ENHERTU–THP2
- 93.7% of patients in the ddAC-THP arm underwent surgery following treatment
- No patients failed to undergo surgery due to an AE
Clinically relevant AR considerations in patients treated with ENHERTU–THP1:
- Serious ARs included COVID-19 (0.9%) and ILD/pneumonitis (0.6%). Fatal ARs occurred in 0.6% of patients, including ILD/pneumonitis and death not otherwise specified (1 patient each)
- The permanent discontinuation of ENHERTU due to ARs was 1.3%, of which ILD/pneumonitis accounted for 0.6%
- Dose interruptions of ENHERTU due to ARs occurred in 11% of patients. The most frequent ARs (>2%) associated with dose interruption of ENHERTU were decreased neutrophil count and COVID-19
- Dose reductions of ENHERTU occurred in 2.5% of patients
With ENHERTU followed by THP in patients with HER2+ eBC in the neoadjuvant setting
Common ARs (≥10% all Grades or ≥2% Grade ≥3) in DESTINY-Breast111
The majority of ARs were Grade 1 or 2
| Adverse Reactions | ENHERTU–THP (n=320) | ddAC-THP (n=312) | |||
|---|---|---|---|---|---|
|
All Grades (%) |
Grade 3-4
(%) |
All
Grades (%) |
Grade 3-4
(%) |
||
|
Gastrointestinal disorders |
Nausea | 65 | 1.9 | 52 | 0.3 |
| Diarrhea | 59 | 6 | 54 | 3.2 | |
| Constipation | 29 | 0.3 | 24 | 0 | |
| Vomiting | 29 | 0.9 | 21 | 0.6 | |
| Stomatitisa | 23 | 0.3 | 36 | 1 | |
| Abdominal painb | 16 | 0 | 12 | 0 | |
|
Nervous system disorders |
Peripheral neuropathyc |
59 | 2.5 | 47 | 2.2 |
| Headached | 18 | 0 | 16 | 0 | |
|
Skin and subcutaneous tissue disorders |
Alopecia | 48 | 0 | 49 | 0 |
| Rashe | 31 | 0.9 | 25 | 1 | |
|
General disorders and administration site conditions |
Fatiguef | 41 | 0.6 | 55 | 2.2 |
|
Musculoskeletal and connective tissue disorders |
Musculoskeletal paing |
30 | 0 | 28 | 0.3 |
|
Metabolism and nutrition disorders |
Decreased appetite | 20 | 0 | 18 | 0.3 |
|
Respiratory, thoracic, and mediastinal disorders |
Epistaxis | 15 | 0 | 10 | 0 |
| Cough | 10 | 0 | 14 | 0 | |
|
Infections and infestations |
Upper respiratory tract infectionh |
13 | 0.6 | 20 | 0.3 |
| COVID-19 | 10 | 0.9 | 11 | 0.3 | |
|
Adverse Reactions |
ENHERTU–THP (n=320) | |
|---|---|---|
|
All Grades (%) |
Grade 3-4
(%) |
|
| Gastrointestinal disorders | ||
| Nausea | 65 | 1.9 |
| Diarrhea | 59 | 6 |
| Constipation | 29 | 0.3 |
| Vomiting | 29 | 0.9 |
| Stomatitisa | 23 | 0.3 |
| Abdominal painb | 16 | 0 |
| Nervous system disorders | ||
|
Peripheral neuropathyc |
59 | 2.5 |
| Headached | 18 | 0 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 48 | 0 |
| Rashe | 31 | 0.9 |
| General disorders and administration site conditions | ||
| Fatiguef | 41 | 0.6 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal paing | 30 | 0 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 20 | 0 |
| Respiratory, thoracic, and mediastinal disorders | ||
| Epistaxis | 15 | 0 |
| Cough | 10 | 0 |
| Infections and infestations | ||
| Upper respiratory tract infectionh | 13 | 0.6 |
| COVID-19 | 10 | 0.9 |
| ddAC-THP (n=312) |
||
|
All Grades (%) |
Grade
3-4
(%) |
|
| Gastrointestinal disorders | ||
| Nausea | 52 | 0.3 |
| Diarrhea | 54 | 3.2 |
| Constipation | 24 | 0 |
| Vomiting | 21 | 0.6 |
| Stomatitisa | 36 | 1 |
| Abdominal painb | 12 | 0 |
| Nervous system disorders | ||
|
Peripheral neuropathyc |
47 | 2.2 |
| Headached | 16 | 0 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 49 | 0 |
| Rashe | 25 | 1 |
| General disorders and administration site conditions | ||
| Fatiguef | 55 | 2.2 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal paing | 28 | 0.3 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 18 | 0.3 |
| Respiratory, thoracic, and mediastinal disorders | ||
| Epistaxis | 10 | 0 |
| Cough | 14 | 0 |
| Infections and infestations | ||
| Upper respiratory tract infectionh | 20 | 0.3 |
| COVID-19 | 11 | 0.3 |
- Premedication: Antiemetics were administered in accordance with standard medical practice and patient tolerance for prophylaxis or management1
- In DESTINY-Breast11, use of 2 or 3 of the following was recommended by the study protocol: a glucocorticoid, serotonin (5-HT3) RA, and a NK1 RA. 16.9% of patients received 3 recommended prophylactic antiemetics before Cycle 1 of ENHERTU–THP (39.7% before Cycle 1 of ddAC-THP); 57.2% of patients received 2 recommended antiemetics before Cycle 1 of ENHERTU–THP (40.4% before Cycle 1 of ddAC-THP). The incidence of nausea events was higher in Cycles 1-4 than in Cycles 5-8 across both treatment arms3
Events were graded using NCI-CTCAE v.5.0.
aIncluding aphthous ulcer, cheilitis, glossitis, mouth ulceration, mucosal inflammation, and stomatitis.
bIncluding abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and gastrointestinal pain.
cIncluding dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, peripheral motor neuropathy, peripheral sensory neuropathy, and polyneuropathy.
dIncluding headache, migraine, and sinus headache.
eIncluding dermatitis, dermatitis acneiform, dermatitis bullous, eczema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, skin exfoliation, and urticarial dermatitis.
fIncluding asthenia, fatigue, and malaise.
gIncluding arthralgia, back pain, bone pain, muscle spasms, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, and pain in extremity.
hIncluding influenza, influenza-like illness, laryngitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection.
With ENHERTU followed by THP in patients with HER2+ eBC in the neoadjuvant setting
Selected laboratory abnormalities in DESTINY-Breast111
The majority of ARs were Grade 1 or 2
| Laboratory parameter | ENHERTU–THP (n=320) | T-DM1 (n=312) | |||
|---|---|---|---|---|---|
|
All Grades (%) |
Grade 3-4
(%) |
All
Grades (%) |
Grade
3-4
(%) |
||
| Hematology |
Decreased hemoglobin |
83 | 2.2 | 97 | 10 |
|
Decreased white blood cell count |
67 | 8 | 87 | 31 | |
|
Decreased neutrophil count |
58 | 17 | 66 | 38 | |
|
Decreased lymphocyte count |
40 | 3.1 | 93 | 39 | |
|
Decreased platelet count |
8 | 0.9 | 28 | 2.9 | |
| Chemistry |
Increased alanine aminotransferase |
79 | 5 | 77 | 4.2 |
|
Increased aspartate aminotransferase |
74 | 2.5 | 68 | 1 | |
|
Decreased blood potassium |
29 | 4.1 | 25 | 4.5 | |
|
Increased blood alkaline phosphatase |
19 | 0 | 24 | 0 | |
|
Decreased sodium |
19 | 1.9 | 23 | 2.6 | |
|
Increased blood creatinine | 8 | 0.6 | 8 | 1.3 | |
|
Increased blood bilirubin |
7 | 0 | 4.2 | 0.6 | |
|
Laboratory parameter |
ENHERTU–THP (n=320) | |
|---|---|---|
|
All Grades (%) |
Grade 3-4
(%) |
|
| Hematology | ||
|
Decreased hemoglobin |
83 | 2.2 |
|
Decreased white blood cell count |
67 | 8 |
|
Decreased neutrophil count |
58 | 17 |
|
Decreased lymphocyte count |
40 | 3.1 |
|
Decreased platelet count |
8 | 0.9 |
| Chemistry | ||
|
Increased alanine aminotrans- ferase |
79 | 5 |
|
Increased aspartate aminotrans- ferase |
74 | 2.5 |
|
Decreased blood potassium |
29 | 4.1 |
|
Increased blood alkaline phosphatase |
19 | 0 |
| Decreased sodium | 19 | 1.9 |
|
Increased blood creatinine |
8 | 0.6 |
|
Increased blood bilirubin |
7 | 0 |
| ddAC-THP (n=312) | ||
|
All Grades (%) |
Grades 3-4 (%) |
|
| Hematology | ||
|
Decreased hemoglobin |
97 | 10 |
|
Decreased white blood cell count |
87 | 31 |
|
Decreased neutrophil count |
66 | 38 |
|
Decreased lymphocyte count |
93 | 39 |
|
Decreased platelet count |
28 | 2.9 |
| Chemistry | ||
|
Increased alanine aminotrans- ferase |
77 | 4.2 |
|
Increased aspartate aminotrans- ferase |
68 | 1 |
|
Decreased blood potassium |
25 | 4.5 |
|
Increased blood alkaline phosphatase |
24 | 0 |
| Decreased sodium | 23 | 2.6 |
|
Increased blood creatinine |
8 | 1.3 |
|
Increased blood bilirubin |
4.2 | 0.6 |
Percentages were calculated using patients with worsening laboratory values from baseline and the number of patients with both baseline and post-treatment measurements as the denominator. Frequencies were based on NCI-CTCAE v.5.0 grade-derived laboratory abnormalities.
Additional safety signals of interest:
- Cardiac disorders: Left ventricular dysfunction was reported in 1.3% of patients receiving ENHERTU–THP (Grade ≥3: 0.3%) and 6.1% of patients receiving ddAC-THP (Grade ≥3: 1.9%)1,2
With ENHERTU followed by THP in patients with HER2+ eBC in the neoadjuvant setting
Early identification of ILD/pneumonitis is key to appropriate management
|
Incidence of
ILD/pneumonitis in DESTINY-Breast114 Incidence of ILD/ pneumonitis in DESTINY- Breast114 |
ENHERTU-THP ENHERTU -THP (n=320) |
ddAC-THP ddAC- THP (n=312) |
|---|---|---|
| All Grades, n (%) | 14 (4.4) | 16 (5.1) |
| Grade 1, n (%) | 4 (1.3) | 4 (1.3) |
| Grade 2, n (%) | 8 (2.5) | 6 (1.9) |
| Grade 3, n (%) | 1 (0.3) | 5 (1.6) |
| Grade 4, n (%) | 0 (0) | 0 (0) |
| Grade 5, n (%)i | 1 (0.3) | 1 (0.3) |
iGrade 5=fatal cases.2
The majority of ILD/pneumonitis cases were Grade 1 or 2 in
DESTINY-Breast112
- Per DESTINY-Breast11 study protocol, patients received high-resolution CT at screening, then additional scans every 6 weeks during neoadjuvant treatment and at 40-day follow-up5
- Scans were reviewed for evidence of ILD/pneumonitis prior to administering each new cycle of ENHERTU–THP5
Management of ARs may require temporary interruption, dose reduction, or treatment discontinuation of ENHERTU as described in the dose reductions table.
Dose modifications were implemented to help manage ARs and
patients' experience while on therapy with ENHERTU–THP
5-HT3, 5-hydroxytryptamine 3; AE, adverse event; AR, adverse reaction; CT, computed tomography; ddAC, dose-dense doxorubicin and cyclophosphamide; eBC, early breast cancer; HER2, human epidermal growth factor receptor 2; ILD, interstitial lung disease; NCI-CTCAE, National Cancer Institute–Common Terminology Criteria for Adverse Events; NK1, neurokinin-1; RA, receptor antagonist; THP, taxane (paclitaxel), trastuzumab, and pertuzumab.
WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY
- Interstitial lung disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
- Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.
INDICATION
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for:
-
HER2-Positive Early Breast Cancer
-
As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP)
-
As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment
-
Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. In the adjuvant HER2+ breast cancer setting, if drug-induced ILD is suspected, rule out radiotherapy-related pneumonitis. If only radiotherapy-related pneumonitis is suspected, consider interruption of ENHERTU for Grade 2 and permanently discontinue ENHERTU for Grade ≥3.
HER2-Positive Breast Cancer and Other Solid Tumors (5.4 mg/kg)
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or pneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.
HER2-Positive Breast Cancer and Other Solid Tumors (5.4 mg/kg)
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, a decrease in neutrophil count was reported in 58% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 42 days (range: 11 to 165). Febrile neutropenia was reported in 0.9% of patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular dysfunction (LVD) has been observed with anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVD through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
HER2-Positive Breast Cancer and Other Solid Tumors (5.4 mg/kg)
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were Grade 3.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.
Adverse Reactions
HER2-Positive Early Breast Cancer
DESTINY-Breast11
The safety of ENHERTU followed by THP was evaluated in 320 patients with HER2-positive (IHC 3+ or ISH+) early breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11. ENHERTU was administered by intravenous infusion once every three weeks for 4 cycles followed by THP for 4 cycles. The median duration of treatment was 5.6 months (range: 0.7 to 9.1) for patients who received ENHERTU followed by THP.
Serious adverse reactions occurred in 11% of patients receiving ENHERTU followed by THP, including COVID-19 (0.9%) and ILD/pneumonitis (0.6%). Fatal adverse reactions occurred in 0.6% of patients, including ILD/pneumonitis and death not otherwise specified (1 patient each).
In patients treated with ENHERTU followed by THP, the permanent discontinuation of ENHERTU due to adverse reactions occurred in 1.3%, of which ILD/pneumonitis accounted for 0.6%. Dose interruptions of ENHERTU due to adverse reactions occurred in 11% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count and COVID-19. Dose reductions of ENHERTU occurred in 2.5% of patients treated with ENHERTU.
The most common (≥20%) adverse reactions in patients treated with ENHERTU followed by THP, including laboratory abnormalities, were decreased hemoglobin (83%), increased alanine aminotransferase (79%), increased aspartate aminotransferase (74%), decreased white blood cell count (67%), nausea (65%), peripheral neuropathy (59%), diarrhea (59%), decreased neutrophil count (58%), alopecia (48%), fatigue (41%), decreased lymphocyte count (40%), rash (31%), musculoskeletal pain (30%), decreased blood potassium (29%), constipation (29%), vomiting (29%), stomatitis (23%), and decreased appetite (20%).
DESTINY-Breast05
The safety of ENHERTU was evaluated in 806 patients with HER2-positive breast cancer with residual invasive disease following neoadjuvant HER2-targeted therapy who then received at least one dose of ENHERTU 5.4 mg/kg. ENHERTU was administered by intravenous infusion once every three weeks for 14 cycles. The median duration of treatment was 10 months (range: 0.7 to 16) for patients who received ENHERTU.
Serious adverse reactions occurred in 17% of patients receiving ENHERTU. Serious adverse reactions in ≥1% of patients who received ENHERTU were ILD/pneumonitis, radiation pneumonitis, pneumonia, and platelet count decreased. Fatal adverse reactions occurred in 0.4% of patients including ILD/pneumonitis (2 patients) and respiratory tract infection (1 patient).
Permanent discontinuation of ENHERTU due to an adverse reaction occurred in 18% of patients. The adverse reaction which resulted in permanent discontinuation of ENHERTU >2% included ILD/pneumonitis. Dose interruptions of ENHERTU due to an adverse reaction occurred in 50% of patients. Adverse reactions which required dosage interruptions in >2% included radiation pneumonitis, neutrophil count decreased, COVID-19, white blood cell count decreased, ILD/pneumonitis, platelet count decreased, upper respiratory tract infection, fatigue, cough, and pyrexia. Dose reductions of ENHERTU due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reductions in >2% of patients included nausea, fatigue, platelet count decreased, ILD/pneumonitis, and neutrophil count decreased.
The most common (≥20%) adverse reactions, including laboratory abnormalities, in patients receiving ENHERTU were decreased white blood cell count (80%), decreased lymphocyte count (72%), decreased neutrophil count (72%), nausea (71%), decreased hemoglobin (61%), increased aspartate aminotransferase (60%), fatigue (54%), increased alanine aminotransferase (53%), decreased platelet count (46%), increased blood alkaline phosphatase (39%), constipation (32%), vomiting (31%), decreased blood potassium (27%), diarrhea (23%), musculoskeletal pain (23%), and decreased appetite (20%).
ILD was reported in 17% of patients receiving ENHERTU, which included COVID-19 pneumonia, interstitial lung disease, lung opacity, organizing pneumonia, pneumocystis jirovecii pneumonia, pneumonia, and pneumonitis which was adjudicated as ILD (irrespective of causality). Adjudicated drug-related ILD for ENHERTU was 10% for all Grades and 0.9% for Grades 3 or 4.
Use in Specific Populations
- Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.
- Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
- Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
- Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
- Geriatric Use: ENHERTU followed by THP: Of the 320 patients with HER2-positive early breast cancer treated with ENHERTU 5.4 mg/kg followed by THP, 12% were ≥65 years and 1.6% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients ≥65 years (38%) as compared to younger patients (30%).
- Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min).
- Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, monitor for increased adverse reactions related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.
Please click here for full Prescribing Information, including Boxed WARNINGS, and click here for Medication Guide.
INDICATION
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for:
-
HER2-Positive Early Breast Cancer
-
As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP)
-
As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment
-
References
- ENHERTU. Prescribing information. Daiichi Sankyo, Inc.; 2026.
- Harbeck N, Modi S, Pusztai L, et al; DESTINY-Breast 11 Trial Investigators. Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): a randomised, open-label, multicentre, phase III trial. Ann Oncol. 2026;37(2):166-179.
- Curigliano G, Harbeck N, Boileau J-F, et al; DESTINY-Breast11 Investigators. DESTINY-Breast11 safety: neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) vs dose-dense doxorubicin + cyclophosphamide followed by THP (ddAC-THP) in high-risk, HER2+ early-stage breast cancer. Presented at: San Antonio Breast Cancer Symposium; December 10, 2025; San Antonio, TX. RF6-02.
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- Data on file. Daiichi Sankyo, Inc. Basking Ridge, NJ.