HER2-low & HER2-ultralow Efficacy Data

In patients with HR+/HER2-low (IHC 1+ or IHC 2+/ISH–) or HER2-ultralow (IHC 0 with membrane staining) mBC

The results of DESTINY-Breast06 extend the potential benefits of HER2-directed therapy to patients with HR+/HER2-ultralow mBC

mPFS in the exploratory HER2-ultralow (IHC 0 with membrane staining) cohort (n=153)^1,2

KM curve depicting 13.2 months mPFS with ENHERTU vs 8.1 months mPFS with chemotherapy in the overall study population, which included patients with HR+/HER2-low (IHC 1+ or IHC 2+/ISH–) or HER2-ultralow (IHC 0 with membrane staining) mBC

The HER2-ultralow cohort was an exploratory population. The data are descriptive and were not tested for statistical significance, nor powered to show a difference between treatment arms. Therefore, the clinical significance of these data cannot be determined

Summary of DESTINY-Breast06 efficacy results by patient population^1,2

	Overall study population (N=866)		HER2-low cohort (n=713)		Exploratory HER2- ultralow cohort (n=153)
	ENHERTU (n=436)	Chemo- therapy (n=430)	ENHERTU (n=359)	Chemo- therapy (n=354)	ENHERTU (n=77)	Chemo- therapy (n=76)
mPFS (mo) (95% CI)	13.2 (12.0, 15.2)	8.1 (7.0, 9.0)	13.2 (11.4, 15.2)	8.1 (7.0, 9.0)	15.1 (10.0, 17.3)	8.3 (5.8, 15.2)
HR (95% CI; P value)	0.64 (0.54, 0.76; P<0.0001)^a		0.62 (0.52, 0.75; P<0.0001)^b		0.76 (0.49, 1.17)
ORR (n; 95% CI)^c	62.6% (246/393; 57.6, 67.4)	34.4% (134/389; 29.7, 39.4)	62% (202/326; 56.5, 67.3)	35.2% (114/324; 30.0, 40.7)	65.7% (44/67; 53.1, 76.8)	30.8% (20/65; 19.9, 43.4)

	Overall study population (N=866)
	ENHERTU (n=436)	Chemo- therapy (n=430)
mPFS (mo) (95% CI)	13.2 (12.0, 15.2)	8.1 (7.0, 9.0)
HR (95% CI; P value)	0.64 (0.54, 0.76; P<0.0001)^a
ORR (n; 95% CI)^c	62.6% (246/393; 57.6, 67.4)	34.4% (134/389; 29.7, 39.4)
	HER2-low cohort (N=713)
	ENHERTU (n=359)	Chemo- therapy (n=354)
mPFS (mo) (95% CI)	13.2 (11.4, 15.2)	8.1 (7.0, 9.0)
HR (95% CI; P value)	0.62 (0.52, 0.75; P<0.0001)^b
ORR (n; 95% CI)^c	62% (202/326; 56.5, 67.3)	35.2% (114/324; 30.0, 40.7)
	Exploratory HER2- ultralow cohort (n=153)
	ENHERTU (n=77)	Chemo- therapy (n=76)
mPFS (mo) (95% CI)	15.1 (10.0, 17.3)	8.3 (5.8, 15.2)
HR (95% CI; P value)	0.76 (0.49, 1.17)
ORR (n; 95% CI)^c	65.7% (44/67; 53.1, 76.8)	30.8% (20/65; 19.9, 43.4)

ORR was not tested for statistical significance and was not powered to show differences between treatment arms. Therefore, the clinical significance of these data cannot be determined

^aBased on unstratified analysis.

^bBased on stratified analysis with stratification factors prior CDK4/6 inhibitor use (yes vs no) and HER2 IHC status of tumor samples (IHC 1+ vs IHC 2+/ISH–).

^cAnalysis was performed based on the patients with measurable disease assessed by BICR at baseline.

Not all HER2 IHC reports will include complete information to inform HER2-low or HER2-ultralow status

To confirm HER2 status, look for the following in HER2 IHC reports^1,3:

Bar chart depicting 62.6% ORR with ENHERTU and 34.4% ORR with chemotherapy in the overall study population, which included patients with HR+/HER2-low (IHC 1+ or IHC 2+/ISH–) or HER2-ultralow (IHC 0 with membrane staining) mBC

This example report has been adapted from the College of American Pathologists Breast Biomarker Reporting Template for HER2 IHC.

^dNot every report may look like this example, so it is important to read all comments and notes.

^eAs demonstrated in DESTINY-Breast06 screening data. Among the 1856 patients screened for participation in the study, 12% (225 patients) had IHC 0 with absent membrane staining, while 22% (402 patients) were classified as HER2-ultralow, defined as IHC 0 with membrane staining. IHC 1+ was observed in 45% (829 patients), and IHC 2+/ISH– in 21% (385 patients).⁴

ADDITIONAL DATA

In patients with HR+/HER2-low (IHC 1+ or IHC 2+/ISH–) and HER2-ultralow (IHC 0 with membrane staining) mBC

Results observed with ENHERTU in select exploratory patient subgroups in the overall study population

EXPLORATORY POST-HOC ANALYSIS

These subgroup data are based on an exploratory post-hoc analysis; they were not tested for statistical significance and not powered to show differences between treatment arms or between subgroups. Therefore, the clinical significance of these data cannot be determined

Median PFS: select subgroup results in the overall study population^2,5

Table depicting exploratory subgroup mPFS results in the overall study population (HR+/HER2 low and HER2-ultralow) across measures of disease burden

EXPLORATORY POST-HOC ANALYSIS

These subgroup data are based on an exploratory post-hoc analysis; they were not tested for statistical significance and not powered to show differences between treatment arms or between subgroups. Therefore, the clinical significance of these data cannot be determined

Confirmed ORR: select subgroup results in the overall study population (BICR)^6,g

Bar chart depicting exploratory subgroup ORR results with ENHERTU (57.9%) and capecitabine (30.7%) in the overall study population (HR+/HER2-low and HER2-ultralow)

Bar chart depicting exploratory subgroup ORR results with ENHERTU (56.5%) and taxanes (31.8%) in the overall study population (HR+/HER2-low and HER2-ultralow)

^fMedian baseline tumor size in the ITT population (per BICR) was 48.6 mm, considering “0” as baseline tumor size for patients without target lesion at baseline.

^gENHERTU and chemotherapy subgroups were matched by physician's choice of chemotherapy before randomization.

^h60% of patients in the chemotherapy arm received capecitabine.

ⁱ40% of patients in the chemotherapy arm received taxanes.

Recommended in NCCN Guidelines text image

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) recommendation for fam-trastuzumab deruxtecan-nxki (ENHERTU) NCCN Guidelines^® recommended option for eligible patients with HR+/HER2-low or HER2-ultralow mBC NCCN Guidelines recommends fam-trastuzumab deruxtecan-nxki (ENHERTU) for recurrent unresectable (local or regional) or stage IV HER2– breast cancer as a Category 2A, 1L other recommended option for patients with HR-positive disease who are in visceral crisis or are endocrine refractory with tumors that are HER2 IHC 0+, 1+ or 2+/ISH-negative and have no germline BRCA1/2 mutation^7,j-l

^jIHC 0+ refers to tumors with faint, partial membrane staining in ≤10% of tumor cells.

^kAssess for germline BRCA1/2 mutations in all patients with recurrent or metastatic breast cancer to identify candidates for PARPi therapy.

^lThe distinction between HER2 test results of IHC 0/absent membrane staining, IHC 0+/with membrane staining (faint, partial membrane staining in ≤10%), IHC 1+, or 2+/ISH negative is currently clinically relevant for therapy selection.

1L, first line; BICR, blinded independent central review; BRCA1/2, BReast CAncer gene 1 or 2; CDK4/6, cyclin-dependent kinases 4 and 6; CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; HR+, hormone receptor-positive; IHC, immunohistochemistry; ISH, in situ hybridization; ITT, intent-to-treat; mBC, metastatic breast cancer; mPFS, median progression-free survival; NCCN, National Comprehensive Cancer Network^® (NCCN^®); ORR, objective response rate; PARPi, poly (adenosine diphosphate-ribose) polymerase inhibitor; PFS, progression-free survival; PR, partial response.

INDICATION AND IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNINGS Expand

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-Low and HER2-Ultralow Metastatic Breast Cancer
- As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting
- As monotherapy 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-authorized 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 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.

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

In patients 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 0.9% 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 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.

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

In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen 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 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.

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

In patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4.

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

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 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, and other clinical trials. Among these patients, 67% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).

HER2-Low and HER2-Ultralow Metastatic Breast Cancer

DESTINY-Breast06
The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU.

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general physical health deterioration (0.2% each).

ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and decreased neutrophil count.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase (41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain (24%).

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 2233 patients treated with ENHERTU 5.4 mg/kg, 28% were ≥65 years and 6% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (56%) 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, 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-Low and HER2-Ultralow Metastatic Breast Cancer
- As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting
- As monotherapy 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-authorized 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.; 2026.
Data on file. Daiichi Sankyo, Inc. Basking Ridge, NJ.
College of American Pathologists. Template for reporting results of biomarker testing of specimens from patients with carcinoma of the breast. Accessed May 18, 2026. https://documents.cap.org/documents/New-Cancer-Protocols-June-2025/Breast.Bmk_1.6.1.0.-REL_CAPCP.pdf
Viale G, Salgado R, Bardia A, et al. HER2-low and HER2-ultralow status determination in tumors of patients with hormone receptor-positive metastatic breast cancer in DESTINY-Breast06. Presented at: European Society for Medical Oncology; September 15, 2024; Barcelona, Spain.
Bardia A, Hu X, Dent R, et al; DESTINY-Breast06 Trial Investigators. Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06. Presented at: San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX.
Barrios CH, Bardia A, Hu X, et al. DESTINY-Breast06 post-hoc analysis by physician’s choice of chemotherapy (TPC): efficacy and safety of trastuzumab deruxtecan (T-DXd) vs TPC in hormone receptor–positive, HER2-low or -ultralow metastatic breast cancer. Presented at: European Society for Medical Oncology Breast Cancer Annual Congress; May 15, 2025; Munich, Germany.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer V.4.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed June 12, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

The results of DESTINY-Breast06 extend the potential benefits of HER2-directed therapy to patients with HR+/HER2-ultralow mBC

mPFS in the exploratory HER2-ultralow (IHC 0 with membrane staining) cohort (n=153)1,2

Summary of DESTINY-Breast06 efficacy results by patient population1,2

Not all HER2 IHC reports will include complete information to inform HER2-low or HER2-ultralow status

Results observed with ENHERTU in select exploratory patient subgroups in the overall study population

Median PFS: select subgroup results in the overall study population2,5

Confirmed ORR: select subgroup results in the overall study population (BICR)6,g

mPFS in the exploratory HER2-ultralow (IHC 0 with membrane staining) cohort (n=153)^1,2

Summary of DESTINY-Breast06 efficacy results by patient population^1,2

Median PFS: select subgroup results in the overall study population^2,5

Confirmed ORR: select subgroup results in the overall study population (BICR)^6,g