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.

Safety Data

Safety data from DESTINY-Breast04 further established the benefit-risk profile in HER2-low mBC¹

The majority of adverse reactions were Grade 1 or 2¹

The median duration of treatment was 8 months (range: 0.2 to 33) with ENHERTU and 3.5 months (range: 0.3 to 17.6) with chemotherapy^1,2
Prophylactic or supportive treatment of treatment-induced adverse reactions was at the discretion of the treating physician and institutional guidelines³

Common adverse reactions (≥10% all Grades or ≥2% Grades 3 or 4) in patients treated with ENHERTU in DESTINY-Breast04¹

Adverse reactions		ENHERTU 5.4 mg/kg (n=371)		Chemotherapy (n=172)
Adverse reactions		All Grades (%)	Grades 3–4 (%)	All Grades (%)	Grades 3–4 (%)
Gastrointestinal disorders	Nausea	76	4.6	30	0
	Vomiting	40	1.6	13	0
	Constipation	34	0.8	22	0
	Diarrhea	27	1.3	22	1.7
	Abdominal pain^a	18	0.5	13	0
	Stomatitis^b	13	0.3	12	0.6
General disorders and administration site conditions	Fatigue^c	54	9	48	4.7
General disorders and administration site conditions	Pyrexia	12	0.3	13	0
Skin and subcutaneous tissue disorders	Alopecia	40	0	33	0
Skin and subcutaneous tissue disorders	Rash^d	13	0	23	4.7
Blood and lymphatic system disorders	Anemia^e	39	10	27	5
Metabolism and nutrition disorders	Decreased appetite	32	2.4	19	1.2
Musculoskeletal and connective tissue disorders	Musculoskeletal pain^f	32	1.3	31	0.6
Investigations	Decreased weight	16	0.3	8	0
Vascular disorders	Hemorrhage^g	16	0	3.5	0
Nervous system disorders	Headache^h	15	0.3	6	0
	Peripheral neuropathyⁱ	13	0	29	5
	Dizziness^j	11	0.5	6	0
Infections and infestations	Upper respiratory tract infection^k	14	0.3	5	0
Respiratory, thoracic, and mediastinal disorders	Interstitial lung disease^l	12	1.3	0.6	0
Respiratory, thoracic, and mediastinal disorders	Dyspnea	10	1.3	9	1.2

Adverse reactions	ENHERTU 5.4 mg/kg (n=371)		Chemo- therapy (n=172)
Adverse reactions	All Grades (%)	Grades 3–4 (%)	All Grades (%)	Grades 3–4 (%)
Gastrointestinal disorders
Nausea	76	4.6	30	0
Vomiting	40	1.6	13	0
Constipation	34	0.8	22	0
Diarrhea	27	1.3	22	1.7
Abdominal pain^a	18	0.5	13	0
Stomatitis^b	13	0.3	12	0.6
General disorders and administration site conditions
Fatigue^c	54	9	48	4.7
Pyrexia	12	0.3	13	0
Skin and subcutaneous tissue disorders
Alopecia	40	0	33	0
Rash^d	13	0	23	4.7
Blood and lymphatic system disorders
Anemia^e	39	10	27	5
Metabolism and nutrition disorders
Decreased appetite	32	2.4	19	1.2
Musculoskeletal and connective tissue disorders
Musculo-skeletal pain^f	32	1.3	31	0.6
Investigations
Decreased weight	16	0.3	8	0
Vascular disorders
Hemorrhage^g	16	0	3.5	0
Nervous system disorders
Headache^h	15	0.3	6	0
Peripheral neuropathyⁱ	13	0	29	5
Dizziness^j	11	0.5	6	0
Infections and infestations
Upper respiratory tract infection^k	14	0.3	5	0
Respiratory, thoracic, and mediastinal disorders
Interstitial lung disease^l	12	1.3	0.6	0
Dyspnea	10	1.3	9	1.2

Events were graded using NCI-CTCAE version 5.0.

^aIncluding abdominal pain, abdominal discomfort, lower abdominal pain, and upper abdominal pain.

^bIncluding stomatitis, aphthous ulcer, mouth ulceration, and pharyngeal inflammation.

^cIncluding fatigue, asthenia, and malaise.

^dIncluding rash, pustular rash, pruritic rash, maculo-papular rash, palmar-plantar erythrodysesthesia syndrome, papular rash, macular rash, eczema, erythema multiforme, dermatitis, urticarial dermatitis, drug eruption, and dermatitis bullous.

^eIncluding anemia, decreased hemoglobin, and decreased red blood cell count.

^fIncluding back pain, myalgia, pain in extremity, musculoskeletal pain, bone pain, musculoskeletal chest pain, arthralgia, noncardiac chest pain, musculoskeletal stiffness, arthritis, spinal pain, and neck pain.

^gIncluding esophageal varices, hemorrhage, hemorrhoidal hemorrhage, epistaxis, hematuria, conjunctival hemorrhage, vaginal hemorrhage, gingival bleeding, genital hemorrhage, eye hemorrhage, hemoptysis, hemorrhagic cystitis, pharyngeal hemorrhage, rectal hemorrhage, upper gastrointestinal hemorrhage, and esophageal hemorrhage.

^hIncluding headache and migraine.

ⁱIncluding peripheral neuropathy, peripheral sensory neuropathy, peripheral motor neuropathy, polyneuropathy, paresthesia, hypoesthesia, dysesthesia, and neuralgia.

^jIncluding dizziness, postural dizziness, and vertigo.

^kIncluding upper respiratory tract infection, influenza, influenza-like illness, nasopharyngitis, pharyngitis, sinusitis, and rhinitis.

^lInterstitial lung disease includes events that were adjudicated as drug-induced ILD for ENHERTU: interstitial lung disease, pneumonitis, organizing pneumonia, pneumonia, and radiation pneumonitis.

Selected laboratory abnormalities in patients in DESTINY-Breast04¹

Laboratory parameter		ENHERTU 5.4 mg/kg (n=371)		Chemotherapy (n=172)
		All Grades (%)	Grades 3–4 (%)	All Grades (%)	Grades 3–4 (%)
		Hematology	Decreased white blood cell count	70	9	78	25
			Decreased hemoglobin	64	8	53	6
Decreased neutrophil count	64		14	73	38
Decreased lymphocyte count	55		18	40	11
Decreased platelet count	44		6	21	0.6
Chemistry	Increased aspartate aminotransferase	38	2.2	38	4.1
	Increased alanine aminotransferase	36	0.8	38	4.1
	Increased blood alkaline phosphatase	34	0.3	24	0
	Decreased blood potassium	25	3.3	17	1.2
	Increased blood bilirubin	16	2.7	15	0.6
	Increased blood creatinine	15	1.1	9	0.6

Laboratory parameter	ENHERTU 5.4 mg/kg (n=371)		Chemo- therapy (n=172)
Laboratory parameter	All Grades (%)	Grades 3–4 (%)	All Grades (%)	Grades 3–4 (%)
Hematology
Decreased white blood cell count	70	9	78	25
Decreased hemoglobin	64	8	53	6
Decreased neutrophil count	64	14	73	38
Decreased lymphocyte count	55	18	40	11
Decreased platelet count	44	6	21	0.6
Chemistry
Increased aspartate aminotransferase	38	2.2	38	4.1
Increased alanine aminotransferase	36	0.8	38	4.1
Increased blood alkaline phosphatase	34	0.3	24	0
Decreased blood potassium	25	3.3	17	1.2
Increased blood bilirubin	16	2.7	15	0.6
Increased blood creatinine	15	1.1	9	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.

Adverse reactions may require dose modifications¹

	ENHERTU 5.4 mg/kg (n=371)	Chemo- therapy (n=172)
Serious adverse reactions^1-3	28%	25%	For ENHERTU, serious ARs in >1% of patients were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to Grade 5 adverse reactions occurred in 4.0% of patients, including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each)¹ For chemotherapy, the most frequent in >1% of patients were dyspnea, febrile neutropenia, fatigue, pleural effusion, neutropenia, disease progression, hepatic failure, hyponatremia, overdose, medication error, colitis, and femur fracture³
Discontinuations due to adverse reactions^1,2,4	16%	8%	For ENHERTU, the most frequent adverse reaction associated with discontinuation was ILD/pneumonitis (8%).¹ Per protocol, ENHERTU was discontinued in DESTINY-Breast04 in patients who were diagnosed with any symptomatic (Grade 2 or greater) ILD¹ For chemotherapy, the most frequent was peripheral sensory neuropathy (2.3%)⁴
Dose interruptions due to adverse reactions^1,3,5	39%	42%	For ENHERTU, the most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia¹ For chemotherapy, the most frequent (>2%) were neutropenia, leukopenia, increased transaminases, palmar-plantar erythrodysesthesia syndrome, fatigue, anemia, nausea, diarrhea, and peripheral sensory neuropathy³
Dose reductions due to adverse reactions^1,3,5	23%	38%	For ENHERTU, the most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia¹ For chemotherapy, the most frequent (>2%) were neutropenia, palmar-plantar erythrodysesthesia syndrome, increased transaminases, fatigue, leukopenia, nausea, and peripheral sensory neuropathy³

Serious adverse reactions^1-3
ENHERTU 5.4 mg/kg (n=371)	28%
Chemotherapy (n=172)	25%
For ENHERTU, serious ARs in >1% of patients were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to Grade 5 adverse reactions occurred in 4.0% of patients, including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each)¹
For chemotherapy, the most frequent in >1% of patients were dyspnea, febrile neutropenia, fatigue, pleural effusion, neutropenia, disease progression, hepatic failure, hyponatremia, overdose, medication error, colitis, and femur fracture³
Discontinuations due to adverse reactions^1,2,4
ENHERTU 5.4 mg/kg (n=371)	16%
Chemotherapy (n=172)	8%
For ENHERTU, the most frequent adverse reaction associated with discontinuation was ILD/pneumonitis (8%).¹ Per protocol, ENHERTU was discontinued in DESTINY-Breast04 in patients who were diagnosed with symptomatic (Grade 2 or greater) ILD¹
For chemotherapy, the most frequent was peripheral sensory neuropathy (2.3%)⁴
Dose interruptions due to adverse reactions^1,3,5
ENHERTU 5.4 mg/kg (n=371)	39%
Chemotherapy (n=172)	42%
For ENHERTU, the most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia¹
For chemotherapy, the most frequent (>2%) were neutropenia, leukopenia, increased transaminases, palmar-plantar erythrodysesthesia syndrome, fatigue, anemia, nausea, diarrhea, and peripheral sensory neuropathy³
Dose reductions due to adverse reactions^1,3,5
ENHERTU 5.4 mg/kg (n=371)	23%
Chemotherapy (n=172)	38%
For ENHERTU, the most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia¹
For chemotherapy, the most frequent (>2%) were neutropenia, palmar-plantar erythrodysesthesia syndrome, increased transaminases, fatigue, leukopenia, nausea, and peripheral sensory neuropathy³

Other clinically relevant adverse reactions reported in ≤10% of patients treated with ENHERTU were cough (10%), dysgeusia (10%), abdominal distension (5%), blurred vision (4.9%), pruritus (3.2%), gastritis (2.7%), skin hyperpigmentation (2.7%), flatulence (2.4%), dehydration (1.9%), febrile neutropenia (1.1%), and infusion-related reactions (0.5%)¹

Incidence of select common adverse reactions in DESTINY-Breast04³

The majority of these adverse reactions were Grade 1 or 2³

Adverse Reactions	ENHERTU 5.4 mg/kg (n=371)
	Grade 1 (%)	Grade 2 (%)	Grade 3 (%)	Grade 4 (%)
	Nausea	43.9	27.5	4.6	0
	Fatigue^m	29.4	18.6	9.4	0
Alopecia	28.6	11.1	0	0
Vomiting	25.9	12.9	1.6	0
Constipation	28.3	4.9	0.5	0.3
Decreased appetite	18.9	10.5	2.4	0
Diarrhea	19.7	5.9	1.3	0

^mIncluding fatigue, asthenia, and malaise.

Drug interaction studies¹

Effect of CYP3A and OATP inhibitors on DXd (clinical studies): There were no clinically meaningful drug-drug interactions between ENHERTU and itraconazole (CYP3A inhibitor), as well as ritonavir (OATP1B/CYP3A inhibitor)
Effect of DXd on CYP enzymes (in vitro studies): DXd did not inhibit common CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A) nor induce CYP1A2, CYP2B6, or CYP3A
Effect of DXd on transporters (in vitro studies): At clinically relevant concentrations, DXd has a low potential to inhibit the transporters OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, MATE1, MATE2-K, P-gp, BCRP, or BSEP
Effect of other drugs on DXd (in vitro studies): DXd is a substrate of OATP1B1, OATP1B3, MATE2-K, P-gp, MRP1, and BCRP

AR, adverse reaction; BCRP, breast cancer resistance protein; BSEP, bile salt export pump; CYP, cytochrome P450; DXd, deruxtecan; HER2, human epidermal growth factor receptor 2; ILD, interstitial lung disease; mBC, metastatic breast cancer; MATE, multidrug and toxic compound extrusion; MRP, multidrug resistance protein; NCI-CTCAE, National Cancer Institute–Common Terminology Criteria for Adverse Events; OAT, organic anion transporter; OATP, organic anion transporting polypeptide; OCT, organic cation transporter; P-gp, P-glycoprotein.

IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNINGS Expand

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

Interstitial lung disease (ILD) and pneumonitis, including 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 the treatment of adult patients with:

Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

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 one 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.

Metastatic Breast Cancer and Other Solid Tumors (5.4 mg/kg)

In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU.

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 one 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 one level.

Metastatic Breast Cancer and Other Solid Tumors (5.4 mg/kg)

In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 63% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease 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.

Metastatic Breast Cancer and Other Solid Tumors (5.4 mg/kg)

In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.8% of patients, of which 0.6% 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 one level.

Adverse Reactions

Metastatic Breast Cancer and Other Solid Tumors (5.4 mg/kg)

The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 1799 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, and other clinical trials. Among these patients, 65% were exposed for >6 months and 38% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (73%), decreased white blood cell count (70%), decreased hemoglobin (66%), decreased neutrophil count (63%), decreased lymphocyte count (58%), fatigue (56%), decreased platelet count (48%), increased aspartate aminotransferase (47%), increased alanine aminotransferase (43%), vomiting (40%), increased blood alkaline phosphatase (38%), alopecia (34%), constipation (33%), decreased appetite (32%), decreased blood potassium (31%), diarrhea (29%), musculoskeletal pain (24%), and abdominal pain (20%).

HER2-Low Metastatic Breast Cancer

DESTINY-Breast04

The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.

Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).

ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%).

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: Of the 1287 patients with breast cancer treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.8% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (59%) as compared to younger patients (49%).
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, closely monitor for increased toxicities 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 the treatment of adult patients with:

Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

References

ENHERTU. Prescribing information. Daiichi Sankyo, Inc.; 2024.
Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20.
Data on file. Daiichi Sankyo, Inc. Basking Ridge, NJ.
Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Protocol for: Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20.
Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Supplement to: Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20.

Safety data from DESTINY-Breast04 further established the benefit-risk profile in HER2-low mBC1

The majority of adverse reactions were Grade 1 or 21

Common adverse reactions (≥10% all Grades or ≥2% Grades 3 or 4) in patients treated with ENHERTU in DESTINY-Breast041

Selected laboratory abnormalities in patients in DESTINY-Breast041

Adverse reactions may require dose modifications1

Incidence of select common adverse reactions in DESTINY-Breast043

The majority of these adverse reactions were Grade 1 or 23

Drug interaction studies1

Safety data from DESTINY-Breast04 further established the benefit-risk profile in HER2-low mBC¹

The majority of adverse reactions were Grade 1 or 2¹

Common adverse reactions (≥10% all Grades or ≥2% Grades 3 or 4) in patients treated with ENHERTU in DESTINY-Breast04¹

Selected laboratory abnormalities in patients in DESTINY-Breast04¹

Adverse reactions may require dose modifications¹

Incidence of select common adverse reactions in DESTINY-Breast04³

The majority of these adverse reactions were Grade 1 or 2³

Drug interaction studies¹