Enhertu Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Enhertu?

Enhertu (fam-trastuzumab deruxtecan-nxki) is a HER2-directed antibody and topoisomerase inhibitor conjugate used to treat 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.

What Are Side Effects of Enhertu?

Side effects of Enhertu include:

nausea,
vomiting,
fatigue,
hair loss,
constipation,
decreased appetite,
anemia,
low white blood cell count (neutropenia, leukopenia),
diarrhea,
cough, and
low platelets (thrombocytopenia),
abdominal pain,
inflammation of the mouth and lips,
indigestion/heartburn,
rash,
low potassium (hypokalemia),
shortness of breath,
nosebleed,
interstitial lung disease,
headache,
dizziness,
upper respiratory tract infection,
increased aspartate aminotransferase,
alanine aminotransferase, and
dry eye

Dosage for Enhertu

The recommended dosage of Enhertu is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

Enhertu In Children

Safety and effectiveness of Enhertu have not been established in pediatric patients.

What Drugs, Substances, or Supplements Interact with Enhertu?

Enhertu may interact with other medicines.

Tell your doctor all medications and supplements you use.

Enhertu During Pregnancy and Breastfeeding

Enhertu is not recommended for use during pregnancy; it may harm a fetus. Females of reproductive potential are advised to use effective contraception during treatment with Enhertu and for at least 7 months following the last dose. Males with female partners of reproductive potential are advised to use effective contraception during treatment with Enhertu and for at least 4 months following the last dose. It is unknown if Enhertu passes into breast milk. Because of the potential for serious adverse reactions in a breastfed child, women are advised not to breastfeed during treatment with Enhertu and for 7 months after the last dose.

Additional Information

Our Enhertu (fam-trastuzumab deruxtecan-nxki) For Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See Slideshow

Enhertu Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

chest tightness, wheezing, cough, new or worsening shortness of breath;
pounding heartbeats or fluttering in your chest;
fever, tiredness, dizziness;
swelling in your lower legs, sudden weight gain;
a light-headed feeling, like you might pass out;
low blood cell counts--fever, chills, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet; or
low potassium level--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

nausea, vomiting, loss of appetite;
diarrhea, constipation;
cough;
fever, feeling tired;
low blood cell counts;
low potassium;
abnormal liver function tests; or
hair loss.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Enhertu (Fam-trastuzumab Deruxtecan-nxki for Injection)

Learn More »

QUESTION

A lump in the breast is almost always cancer. See Answer

Enhertu Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

Interstitial Lung Disease/Pneumonitis [see WARNINGS AND PRECAUTIONS]
Neutropenia [see WARNINGS AND PRECAUTIONS]
Left Ventricular Dysfunction [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Metastatic Breast Cancer

The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201A-J101 (NCT02564900) [see Clinical Studies]. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

In the pooled 234 patients, the median age was 56 years (range: 28-96), 74% of patients were <65 years, 99.6% of patients were female, and the majority were White (51%) or Asian (42%). Patients had an ECOG performance status of 0 (58%) or 1 (42%) at baseline. Ninety-four percent had visceral disease, 31% had bone metastases, and 13% had brain metastases.

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea, white blood cell count decreased, hemoglobin decreased, neutrophil count decreased, fatigue, vomiting, alopecia, aspartate aminotransferase increased, alanine aminotransferase increased, platelet count decreased, constipation, decreased appetite, anemia, diarrhea, hypokalemia, and cough.

Tables 3 and 4 summarize common adverse reactions and laboratory abnormalities observed in ENHERTU-treated patients.

Table 3: Common Adverse Reactions (≥10% All Grades or ≥2% Grades 3 or 4) in Patients in DESTINY-Breast01 and Study DS8201-A-J101

Adverse Reactions	ENHERTU 5.4 mg/kg N=234
Adverse Reactions	All Grades %	Grades 3 or 4 %
Gastrointestinal Disorders
Nausea	79	7
Vomiting	47	3.8
Constipation	35	0.9
Diarrhea	29	1.7
Abdominal pain^a	19	1.3
Stomatitis^b	14	0.9
Dyspepsia	12	0
General Disorders and Administration Site Conditions
Fatigue^c	59	6
Skin and Subcutaneous Tissue Disorders
Alopecia	46	0.4^d
Rash^e	10	0
Metabolism and Nutrition Disorders
Decreased appetite	32	1.3
Blood and Lymphatic System Disorders
Anemia^f	31	7
Respiratory, Thoracic and Mediastinal Disorders
Cough	20	0
Dyspnea	13	1.3
Epistaxis	13	0
Interstitial lung disease^g	9	2.6^h
Nervous System Disorders
Headacheⁱ	19	0
Dizziness	10	0
Infections and Infestation
Upper respiratory tract infection^j	15	0
Eye Disorders
Dry eye	11	0.4^k
Events were graded using NCI CTCAE version 4.03. N = number of patients exposed; PT = preferred term. Percentages were calculated using the number of patients in the Safety Analysis Set as the denominator. ^a Grouped term of abdominal pain includes PTs of abdominal discomfort, gastrointestinal pain, abdominal pain, abdominal pain lower, and abdominal pain upper. ^b Grouped term of stomatitis includes PTs of stomatitis, aphthous ulcer, mouth ulceration, oral mucosa erosion, and oral mucosa blistering. One Grade 1 event of aphthous ulcer was not included in the summary of grouped term stomatitis (from DESTINY-Breast01). ^c Grouped term of fatigue includes PTs of fatigue and asthenia. ^d This Grade 3 event was reported by the investigator. Per NCI CTCAE v.4.03, the highest NCI CTCAE grade for alopecia is Grade 2. ^e Grouped term of rash includes PTs of rash, rash pustular, and rash maculo-papular. ^f Grouped term of anemia includes PTs of anemia, hemoglobin decreased, hematocrit decreased, and red blood cell count decreased. ^g Interstitial lung disease includes events that were adjudicated as ILD: pneumonitis, interstitial lung disease, respiratory failure, organizing pneumonia, acute respiratory failure, lung infiltration, lymphangitis, and alveolitis. ^h All events had fatal outcomes (n=6). ⁱ Grouped term of headache includes PTs of headache, sinus headache, and migraine. ^j Grouped term of upper respiratory tract infection includes PTs of influenza, influenza-like illness, and upper respiratory tract infection. ^k This Grade 4 event was reported by the investigator. Per NCI CTCAE v.4.03, the highest NCI CTCAE grade for dry eye is Grade 3.

Other clinically relevant adverse reactions reported in less than 10% of patients were:

Injury, Poisoning and Procedural Complications: infusion-related reactions (2.6%)

Blood and Lymphatic System Disorders: febrile neutropenia (1.7%)

Table 4: Selected Laboratory Abnormalities in Patients with Unresectable or Metastatic HER2-positive BreastCancer Treated with ENHERTU

Laboratory Parameter	ENHERTU 5.4 mg/kg N=234
Laboratory Parameter	All Grades %	Grades 3 or 4 %
Hematology
White blood cell count decreased	70	7
Hemoglobin decreased	70	7
Neutrophil count decreased	62	16
Platelet count decreased	37	3.4
Chemistry
Aspartate aminotransferase increased	41	0.9
Alanine aminotransferase increased	38	0.4
Hypokalemia	26	3
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.4.03 grade-derived laboratory abnormalities.

Locally Advanced Or Metastatic Gastric Cancer

The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01 [see Clinical Studies]. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m² biweekly or paclitaxel (N=7) 80 mg/m² weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased, white blood cell decreased, neutrophil count decreased, lymphocyte count decreased, platelet count decreased, nausea, decreased appetite, anemia, aspartate aminotransferase increased, fatigue, blood alkaline phosphatase increased, alanine aminotransferase increased, diarrhea, hypokalemia, vomiting, constipation, blood bilirubin increased, pyrexia, and alopecia.

Tables 5 and 6 summarize adverse reactions and laboratory abnormalities observed in patients receiving ENHERTU 6.4 mg/kg in DESTINY-Gastric01.

Table 5: Adverse Reactions in ≥10% All Grades or ≥2% Grades 3 or 4 of Patients Receiving ENHERTU in DESTINY-Gastric01

Adverse Reactions	ENHERTU 6.4 mg/kg N=125		Irinotecan or Paclitaxel N=62
Adverse Reactions	All Grades %	Gra des 3 or 4%	All Grades %	Grades 3 or 4 %
Gastrointestinal Disorders
Nausea	63	4.8	47	1.6
Diarrhea	32	2.4	32	1.6
Vomiting	26	0	8	0
Constipation	24	0	23	0
Abdominal pain^a	14	0.8	15	3.2
Stomatitis^b	11	1.6	4.8	0
Metabolism and Nutrition Disorders
Decreased appetite	60	17	45	13
Dehydration	6	2.4	3.2	1.6
Blood and Lymphatic System Disorders
Anemia^c	58	38	31	23
Febrile neutropenia	4.8	4.8	3.2	3.2
General Disorders and Administration Site Conditions
Fatigue^d	55	9	44	4.8
Pyrexia	24	0	16	0
Edema peripheral	10	0	0	0
Skin and Subcutaneous Tissue Disorders
Alopecia	22	0	15	0
Respiratory, Thoracic and Mediastinal Disorders
Interstitial lung disease^e	10	2.4	0	0
Hepatobiliary Disorders
Hepatic function abnormal	8	3.2	1.6	1.6
Events were graded using NCI CTCAE version 4.03. N = number of patients exposed; PT = preferred term. Percentages were calculated using the number of patients in the Safety Analysis Set as the denominator. ^aGrouped term of abdominal pain includes PTs of abdominal discomfort, gastrointestinal pain, abdominal pain, abdominal pain lower, and abdominal pain upper. ^b Grouped term of stomatitis includes PTs of stomatitis, aphthous ulcer, mouth ulceration, oral mucosa erosion, and oral mucosal blistering. ^c Grouped term of anemia includes PTs of anemia, hemoglobin decreased, red blood cell count decreased, and hematocrit decreased. ^d Grouped term of fatigue includes PTs of fatigue, asthenia, and malaise. ^e Interstitial lung disease includes events that were adjudicated as ILD: pneumonitis, interstitial lung disease, respiratory failure, organizing pneumonia, acute respiratory failure, lung infiltration, lymphangitis, and alveolitis.

Other clinically relevant adverse reactions reported in less than 10% of patients were:

Cardiac Disorders: asymptomatic left ventricular ejection fraction decrease (8%) [see WARNINGS AND PRECAUTIONS]

Infections and Infestations: pneumonia (6%)

Injury, Poisoning and Procedural Complications: infusion-related reactions (1.6%)

Table 6: Selected Laboratory Abnormalities Occurring in Patients Receiving ENHERTU in DESTINY-Gastric01

Laboratory Parameter	ENHERTU 6.4 mg/kg N=125		Irinotecan or Paclitaxel N=62
Laboratory Parameter	All Grades %	Grades 3 or 4 %	All Grades %	Grades 3 or 4 %
Hematology
Hemoglobin decreased	75	38	55	23
White blood cell count decreased	74	29	53	13
Neutrophil count decreased	72	51	45	23
Lymphocyte count decreased	70	28	53	12
Platelet count decreased	68	12	12	5
Chemistry
Aspartate aminotransferase increased	58	9	32	8
Blood alkaline phosphatase increased	54	8	34	10
Alanine aminotransferase increased	47	9	17	1.7
Hypokalemia	30	4.8	18	8
Blood bilirubin increased	24	7	5	3.4
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.4.03 grade-derived laboratory abnormalities.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparisons of the incidence of antibodies to ENHERTU in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Treatment-induced anti-fam-trastuzumab deruxtecan-nxki antibodies (ADA) developed in 1.7% (14/807) patients who received ENHERTU across all doses. Due to the limited number of patients who tested positive for ADA, no conclusions can be drawn concerning a potential effect of immunogenicity on efficacy or safety. In addition, neutralizing activity of anti-ENHERTU antibodies has not been assessed.

Read the entire FDA prescribing information for Enhertu (Fam-trastuzumab Deruxtecan-nxki for Injection)

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