ENHERTU® Approved in the U.S. as First HER2 Directed Therapy for Patients with HER2 Low or HER2 Ultralow Metastatic Breast Cancer Following Disease Progression After One or More Endocrine Therapies
ENHERTU® has received FDA approval as the first HER2-directed therapy for patients with HER2 low or HER2 ultralow metastatic breast cancer who experienced disease progression after endocrine therapy. The approval is based on the DESTINY-Breast06 phase 3 trial, where ENHERTU showed:
- 36% reduction in disease progression or death risk vs chemotherapy
- Median progression-free survival of 13.2 months vs 8.1 months with chemotherapy
- 62.6% objective response rate vs 34.4% with chemotherapy
- 14.3 months median duration of response vs 8.6 months with chemotherapy
The drug, jointly developed by Daiichi Sankyo and AstraZeneca, received Priority Review and Breakthrough Therapy Designation. Following this approval, AstraZeneca will pay Daiichi Sankyo a $175 million milestone payment.
ENHERTU® ha ricevuto l'approvazione della FDA come prima terapia mirata al HER2 per pazienti con cancro al seno metastatico HER2 a bassa o ultrabassa espressione che hanno mostrato progressione della malattia dopo la terapia endocrina. L'approvazione si basa sul trial di fase 3 DESTINY-Breast06, dove ENHERTU ha mostrato:
- Una riduzione del 36% del rischio di progressione della malattia o di morte rispetto alla chemioterapia
- Una mediana di sopravvivenza libera da progressione di 13,2 mesi rispetto a 8,1 mesi con la chemioterapia
- Un tasso di risposta oggettiva del 62,6% rispetto al 34,4% con la chemioterapia
- Una durata mediana di risposta di 14,3 mesi rispetto a 8,6 mesi con la chemioterapia
Il farmaco, sviluppato congiuntamente da Daiichi Sankyo e AstraZeneca, ha ricevuto la Revisione Prioritaria e la Designazione di Terapia Innovativa. A seguito di questa approvazione, AstraZeneca effettuerà un pagamento di $175 milioni a Daiichi Sankyo.
ENHERTU® ha recibido la aprobación de la FDA como la primera terapia dirigida a HER2 para pacientes con cáncer de mama metastásico HER2 bajo o ultrabajo que experimentaron progresión de la enfermedad tras la terapia endocrina. La aprobación se basa en el ensayo de fase 3 DESTINY-Breast06, donde ENHERTU mostró:
- Una reducción del 36% en el riesgo de progresión de la enfermedad o muerte en comparación con la quimioterapia
- Una mediana de supervivencia libre de progresión de 13,2 meses frente a 8,1 meses con quimioterapia
- Una tasa de respuesta objetiva del 62,6% frente al 34,4% con quimioterapia
- Una duración media de respuesta de 14,3 meses frente a 8,6 meses con quimioterapia
El fármaco, desarrollado conjuntamente por Daiichi Sankyo y AstraZeneca, recibió la Revisión Prioritaria y la Designación de Terapia Innovadora. Tras esta aprobación, AstraZeneca pagará a Daiichi Sankyo un importe de 175 millones de dólares.
ENHERTU®는 내분비 요법 이후 질병 진행을 경험한 HER2 저용량 또는 HER2 초저용량 전이성 유방암 환자를 위한 최초의 HER2 표적 치료제로 FDA 승인을 받았습니다. 이 승인은 DESTINY-Breast06 3상 시험에 근거하고 있으며, ENHERTU는 다음과 같은 결과를 보여주었습니다:
- 화학요법 대비 질병 진행 또는 사망 위험 36% 감소
- 화학요법과 비교하여 중위 무진행 생존기간 13.2개월 대 8.1개월
- 화학요법과 비교하여 객관적 반응률 62.6% 대 34.4%
- 화학요법과 비교하여 중위 반응 지속기간 14.3개월 대 8.6개월
이 약물은 다이이치 산쿄(Daiichi Sankyo)와 아스트라제네카(AstraZeneca)가 공동 개발하였으며, 우선 심사 및 혁신적인 치료법으로 지정받았습니다. 이번 승인을 따라 아스트라제네카는 다이이치 산쿄에 1억 7,500만 달러의 마일스톤 지급을 할 것입니다.
ENHERTU® a reçu l'approbation de la FDA en tant que première thérapie ciblée HER2 pour les patients atteints de cancer du sein métastatique HER2 faible ou HER2 ultrafaible qui ont connu une progression de la maladie après un traitement endocrinien. L'approbation est basée sur l'essai de phase 3 DESTINY-Breast06, où ENHERTU a montré :
- Une réduction de 36 % du risque de progression de la maladie ou de décès par rapport à la chimiothérapie
- Une survie médiane sans progression de 13,2 mois contre 8,1 mois avec chimiothérapie
- Un taux de réponse objective de 62,6 % contre 34,4 % avec chimiothérapie
- Une durée médiane de réponse de 14,3 mois contre 8,6 mois avec chimiothérapie
Le médicament, développé conjointement par Daiichi Sankyo et AstraZeneca, a reçu une révision prioritaire et une désignation de thérapie révolutionnaire. À la suite de cette approbation, AstraZeneca versera à Daiichi Sankyo un paiement d'étape de 175 millions de dollars.
ENHERTU® hat die FDA-Zulassung als erste HER2-direktive Therapie für Patienten mit HER2 niedrig oder HER2 ultraniedrig metastasierendem Brustkrebs erhalten, die nach einer endokrinen Therapie ein Fortschreiten der Erkrankung erfuhren. Die Zulassung basiert auf der DESTINY-Breast06 Phase-3-Studie, in der ENHERTU folgende Ergebnisse zeigte:
- 36% Verringerung des Risikos für das Fortschreiten der Erkrankung oder Tod im Vergleich zur Chemotherapie
- Median der progressionsfreien Überlebenszeit von 13,2 Monaten im Vergleich zu 8,1 Monaten mit Chemotherapie
- 62,6% objektive Ansprechrate im Vergleich zu 34,4% mit Chemotherapie
- Median der Ansprechdauer von 14,3 Monaten im Vergleich zu 8,6 Monaten mit Chemotherapie
Das Medikament, das von Daiichi Sankyo und AstraZeneca gemeinsam entwickelt wurde, erhielt eine priorisierte Überprüfung sowie die Durchbruchtherapie-Zulassung. Nach dieser Genehmigung wird AstraZeneca Daiichi Sankyo eine Meilenstein-Zahlung in Höhe von 175 Millionen US-Dollar leisten.
- 36% reduction in disease progression or death risk compared to chemotherapy
- Significantly higher median progression-free survival (13.2 vs 8.1 months)
- Superior objective response rate (62.6% vs 34.4%)
- $175 million milestone payment to be received from AstraZeneca
- FDA Priority Review and Breakthrough Therapy Designation obtained
- 20% of patients experienced serious adverse reactions
- 2.8% fatality rate due to adverse reactions
- Multiple significant side effects reported including decreased blood cell counts and liver function abnormalities
Insights
The FDA approval of ENHERTU for HER2 low/ultralow metastatic breast cancer marks a transformative milestone in breast cancer treatment. The expansion into earlier treatment lines, specifically post-endocrine therapy, significantly broadens the addressable market. Key performance metrics are compelling:
- A 36% reduction in disease progression risk
- 13.2 months median PFS versus 8.1 months for chemotherapy
- An impressive 62.6% ORR with meaningful complete responses
This approval is particularly significant as it positions ENHERTU as the first HER2-directed therapy for this patient population, creating a new standard of care. The inclusion of both HER2 low and ultralow expressions effectively doubles the targetable patient population, representing a substantial market opportunity.
The
The DESTINY-Breast06 data represents a scientific breakthrough in breast cancer treatment paradigms. The study's success in treating even HER2 ultralow patients (IHC 0 with membrane staining) challenges traditional HER2 expression thresholds and treatment approaches. Notable scientific achievements include:
- Consistent efficacy across HER2 expression levels, including ultralow (15.1 months PFS)
- Superior response rates in both populations (62.0% in HER2 low, 65.7% in ultralow)
- Durable responses exceeding 14 months
The safety profile, while requiring monitoring for ILD/pneumonitis, aligns with previous ENHERTU studies. The ability to effectively treat patients previously considered HER2-negative represents a paradigm shift in breast cancer classification and treatment selection. This approval validates the concept that even minimal HER2 expression can serve as a therapeutic target, potentially influencing future drug development approaches in oncology.
- Based on DESTINY-Breast06 phase 3 trial results which showed ENHERTU demonstrated superiority versus chemotherapy with a median progression-free survival of more than one year
- Approval brings Daiichi Sankyo and AstraZeneca’s ENHERTU to an earlier HR positive treatment setting and broadens the patient population eligible for treatment with a HER2 directed therapy to those with HER2 ultralow disease
ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.
This approval, which is based on results from the DESTINY-Breast06 phase 3 trial presented at the 2024 American Society of Clinical Oncology (#ASCO24) Annual Meeting and published in The New England Journal of Medicine, follows Priority Review and Breakthrough Therapy Designation by the FDA for ENHERTU in this indication.
In the DESTINY-Breast06 trial, ENHERTU demonstrated a
The confirmed objective response rate (ORR) in the overall trial population was
In the HER2 low population (n=713) (HR 0.62;
An exploratory analysis of the HER2 ultralow population (n=153) (HR 0.76;
“Endocrine therapy is typically used in the initial treatment of HR positive metastatic breast cancer and following progression, subsequent chemotherapy is associated with poor outcomes,” said Aditya Bardia, MD, MPH, Program Director of Breast Oncology and Director of Translational Research Integration, UCLA Health Jonsson Comprehensive Cancer Center and Investigator in the DESTINY-Breast06 trial. “With a median progression-free survival exceeding one year and a response rate of more than 60 percent, trastuzumab deruxtecan offers a potential new standard of care for patients with hormone receptor positive, HER2 low or HER2 ultralow metastatic breast cancer following endocrine therapy.”
“We are excited to see more treatment options for these patients which enable more personalized care,” said Krissa Smith, Vice President, Education, Susan G. Komen. “It is critical for patients to understand the HER2 status of their metastatic breast cancer to help them make informed treatment decisions. Patients with tumors that are HER2 low or HER2 ultralow now have more options to consider with their healthcare team.”
ENHERTU is approved with Boxed WARNINGS for interstitial lung disease (ILD)/pneumonitis and Embryo-Fetal toxicity. 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) in DESTINY-Breast06. The most common (≥
“ENHERTU continues to redefine the classification and treatment of HR positive metastatic breast cancer with important new data across the spectrum of HER2 expression,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “Today’s approval underscores our ongoing commitment to realizing the full potential of this innovative antibody drug conjugate and represents another paradigm shift in how certain breast cancers can be treated.”
“Building on the practice-changing previous approvals for ENHERTU, this new approval brings this important medicine to an earlier treatment setting and a broader patient population with HER2 expressing metastatic breast cancer,” said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. “The approval also highlights the importance of testing metastatic breast cancer tumors for detectable staining with a standard IHC test to identify those who may be eligible for treatment with ENHERTU following endocrine therapy.”
Daiichi Sankyo and AstraZeneca are committed to ensuring that patients in the
Please visit www.ENHERTU.com for full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
Financial Considerations
Following this approval in the
About DESTINY-Breast06
DESTINY-Breast06 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab paclitaxel) in patients with HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients also were eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting first-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months.
HER2 IHC status was confirmed by a central laboratory and determined based on the most recent evaluable HER2 IHC sample prior to randomization. In tumor samples from patients screened for trial eligibility, nearly two-thirds of tumors previously assessed as IHC 0 at a local laboratory were re-classified as HER2 low or HER2 ultralow upon central analysis of the archival tumor sample. It was also observed that approximately
The primary endpoint of DESTINY-Breast06 is PFS in the HR positive, HER2 low patient population as measured by BICR. Key secondary endpoints include PFS by BICR in the overall trial population (HER2 low and HER2 ultralow), OS in patients in the HER2 low patient population and OS in the overall trial population. Other secondary endpoints include ORR, DOR, time to first subsequent treatment or death, time to second subsequent treatment or death and safety. Analysis of the HER2 ultralow subgroup was not powered to demonstrate statistical significance.
DESTINY-Breast06 enrolled 866 patients (n=713 for HER2 low and n=153 for HER2 ultralow) in
About Breast Cancer and HER2 Expression
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.1 In the
HR positive, HER2 negative is the most common breast cancer subtype, accounting for approximately
Endocrine therapy is widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer. However, after initial therapy, further efficacy with additional endocrine treatment is often limited.7 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.7,8,9,10
Prior to the approvals of ENHERTU in HER2 low and HER2 ultralow metastatic breast cancer based on the DESTINY-Breast04 and DESTINY-Breast06 trials, there were no targeted therapies approved specifically for these patient populations.11,12
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the
ENHERTU (5.4 mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
ENHERTU (5.4 mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
ENHERTU (5.4 mg/kg) is approved in the
ENHERTU (5.4 mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in
ENHERTU (6.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in
ENHERTU (5.4 mg/kg) is approved in
About the ENHERTU Clinical Development Program
A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and DATROWAY® in July 2020, except in
About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.
The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc,
The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.
Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
ENHERTU
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
-
Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either:
– In the metastatic setting, or
– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
-
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-approved test, that has progressed on one or more endocrine therapies in the metastatic setting
– 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
-
Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
- Locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen
-
Unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY
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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.
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in
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, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in
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 >
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography,
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, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (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, DESTINYBreast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients,
HER2-Positive Metastatic Breast Cancer
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU.
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
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
ENHERTU was permanently discontinued in
The most common (≥
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
ENHERTU was permanently discontinued in
The most common (≥
HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)
DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.
The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY-Lung02. Nineteen percent of patients were exposed for >6 months.
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 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) for patients who received ENHERTU.
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2).
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
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.
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Geriatric Use: Of the 1741 patients with HER2-positive, HER2-low, or HER2-ultralow breast cancer treated with ENHERTU 5.4 mg/kg,
24% were ≥65 years and4.9% 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 (61% ) as compared to younger patients (52% ). Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU 5.4 mg/kg,40% were ≥65 years and8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01,56% were ≥65 years and14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 192 patients with HER2-positive (IHC 3+) unresectable or metastatic solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02, DESTINY-Lung01, or DESTINY-CRC02,39% were ≥65 years and9% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. - 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 see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
About Daiichi Sankyo
Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com.
References:
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1 Bray F, et al. CA Cancer J Clin. 2024; 10.3322/caac.21834.
2 American Cancer Society. Key Statistics for Breast Cancer. Accessed January 2025.
3 National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Accessed January 2025.
4 Iqbal N, et al. Mol Biol Int. 2014;852748.
5 Ahn S, et al. J Pathol Transl Med. 2020;54(1):34-44.
6 Sajjadi E, et al. Cancer Drug Resist. 2022;5(4):882-888.
7 Manohar P, et al. Cancer Biol Med. 2022 Feb 15; 19(2):202–212.
8 Cortes J, et al. Lancet. 2011;377:914-923.
9 Yuan P, et al. Eur J Cancer. 2019;112:57-65.
10 Jerusalem G, et al. JAMA Oncol. 2018;4(10):1367–1374.
11 Modi S, et al. N Engl J Med. 2022;387:9-20.
12 Eiger D, et al. Cancers. 2021 Mar; 13(5): 1015.
PP-US-ENB-3661
01/25
View source version on businesswire.com: https://www.businesswire.com/news/home/20250122766906/en/
Media Contacts:
Global/US:
Jennifer Brennan
Daiichi Sankyo, Inc.
jennifer.brennan@daiichisankyo.com
+1 908 900 3183 (mobile)
Daiichi Sankyo Co., Ltd.
DS-PR_jp@daiichisankyo.com
Investor Relations Contact:
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Source: Daiichi Sankyo
FAQ
What are the key efficacy results of ENHERTU in the DESTINY-Breast06 trial for AZN?
What is the milestone payment AZN will make for this ENHERTU approval?
What are the main safety concerns for ENHERTU in the AZN breast cancer treatment?
How does ENHERTU perform in HER2 ultralow breast cancer patients for AZN?
