ENHERTU® Demonstrated a Median Progression-Free Survival of 13.2 Months in HR Positive, HER2 Low and HER2 Ultralow Metastatic Breast Cancer Following One or More Lines of Endocrine Therapy
ENHERTU® demonstrated a median progression-free survival (PFS) of 13.2 months in HR positive, HER2 low and ultralow metastatic breast cancer patients following one or more lines of endocrine therapy, as shown in the DESTINY-Breast06 trial. The results showed a 38% reduction in the risk of disease progression or death compared to chemotherapy, with a statistically significant improvement in PFS. The overall response rate (ORR) was 57.3% with ENHERTU versus 31.2% with chemotherapy. These findings suggest that ENHERTU could become a new standard of care for this patient group. The trial also highlighted the safety profile of ENHERTU, which was consistent with previous trials.
- ENHERTU demonstrated a median PFS of 13.2 months.
- Significant 38% reduction in the risk of disease progression or death with ENHERTU.
- ORR of 57.3% with ENHERTU compared to 31.2% with chemotherapy.
- ENHERTU showed potential to become a new standard of care for HR positive, HER2 low, and ultralow metastatic breast cancer.
- Safety profile consistent with previous clinical trials.
- Interstitial lung disease or pneumonitis occurred in 11.3% of patients treated with ENHERTU.
- Grade 3 or higher treatment-related adverse events included neutropenia (20.7%), leukopenia (6.9%), and anemia (5.8%).
- Three grade 5 ILD events were reported, leading to death in 0.7% of patients.
ENHERTU's results from the DESTINY-Breast06 trial have shown substantial progress for patients with HR positive, HER2 low and HER2 ultralow metastatic breast cancer. A median progression-free survival (PFS) of 13.2 months compared to 8.1 months with standard chemotherapy indicates a significant potential benefit.
The fact that ENHERTU is the first HER2 directed antibody drug conjugate (ADC) to show such a benefit in this setting is notable. The drug's ability to reduce the risk of disease progression or death by
In oncology, progression-free survival is a critical measure as it indicates how long a patient lives without the cancer worsening. The high objective response rate (ORR) of 56.5% in the HER2 low population compared to 32.2% with chemotherapy further reinforces ENHERTU's efficacy.
Another key takeaway is the promising results within the HER2 ultralow subgroup, showing a 22% reduction in risk of progression or death. This expands the drug's potential application to a broader patient base who previously had fewer targeted treatment options.
For retail investors, it’s essential to recognize that these clinical results can lead to improved market adoption and higher demand for ENHERTU, translating to potential growth for Daiichi Sankyo and AstraZeneca in both the short and long term.
The positive clinical trial results of ENHERTU suggest strong growth potential for Daiichi Sankyo and AstraZeneca. The reduction in disease progression or death by
From a financial perspective, this positions ENHERTU as a potential new standard of care in the treatment landscape for HER2 low and ultralow expressing tumors. This should drive substantial revenue growth for both companies. Consider that existing treatments have not met this level of efficacy, indicating a robust market opportunity.
Investors should also pay attention to the expansion into new patient populations, such as those with HER2 ultralow expression. This can significantly increase the addressable market, thus improving the financial outlook for both companies involved.
It’s essential to monitor follow-up data and any potential competitive responses, but the promising figures from the DESTINY-Breast06 trial present a positive outlook for ENHERTU’s revenue potential.
The DESTINY-Breast06 trial confirms the efficacy of ENHERTU in treating HR positive, HER2 low and HER2 ultralow metastatic breast cancer. The improvement in progression-free survival (PFS) to 13.2 months compared to 8.1 months is a critical metric for assessing treatment effectiveness.
ENHERTU's mechanism as an antibody drug conjugate (ADC) specifically targeting HER2, even at low levels of expression, showcases its innovative approach. The statistically significant results reinforce its potential as a transformative therapy in the oncology field.
Moreover, the safety profile remains consistent with previous trials, with manageable adverse events. Notably, the interstitial lung disease (ILD) occurrence was low, which is vital for patient compliance and long-term treatment success.
For investors, understanding the clinical implications helps in appreciating the drug’s market potential and its impact on the companies' long-term valuation. Continued positive results could lead to broader regulatory approvals and increased market penetration.
- DESTINY-Breast06 results show Daiichi Sankyo and AstraZeneca’s ENHERTU is the first HER2 directed medicine and antibody drug conjugate to demonstrate clinically meaningful benefit for patients in this setting
- Additionally, data from DESTINY-Breast03 and DESTINY-Breast07 trials in HER2 positive metastatic breast cancer reinforce ENHERTU as standard of care in second-line setting and highlight potential in first-line setting
ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).
In the primary endpoint analysis of patients with HR positive, HER2 low metastatic breast cancer, ENHERTU reduced the risk of disease progression or death by
In the key secondary endpoint analysis of PFS by BICR in the overall trial population, ENHERTU achieved a similar
A prespecified exploratory analysis showed the clinically meaningful improvement in PFS was consistent between patients with HER2 low and HER2 ultralow expression. In patients with HER2 ultralow expression, ENHERTU showed a
In patients with HER2 low expression, confirmed objective response rate (ORR) was
“Endocrine therapies are widely used early in the treatment of HR positive metastatic breast cancer, but following one or more lines of treatment, patients often derive limited efficacy from further endocrine-based therapy,” said Giuseppe Curigliano, MD, PhD, Professor of Medical Oncology at the University of
The safety profile of ENHERTU in DESTINY-Breast06 was consistent with previous breast cancer clinical trials with no new safety concerns identified. The most common grade 3 or higher treatment related treatment emergent adverse events (TEAEs) occurring in
“ENHERTU continues to deliver pioneering results for a HER2 directed medicine across many different types of cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “These latest results from DESTINY-Breast06 demonstrate clinically meaningful results with ENHERTU even in tumors with very low levels of HER2 expression, suggesting that it may have an important role in treating a wide range of HER2 expressing metastatic breast cancer.”
“DESTINY-Breast06 represents another potential paradigm shift in how we treat patients across the spectrum of HR positive metastatic breast cancer,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “The results reinforce the potential for ENHERTU to improve outcomes earlier in the treatment landscape and in a broader population of patients with HER2 expressing breast cancer who have never before been eligible for a HER2 directed therapy.”
Patients in the DESTINY-Breast06 trial received a median of two prior lines of endocrine therapy in each treatment arm. In the overall trial population,
Summary of DESTINY-Breast06 Primary Analysis Results
Efficacy Measure |
HER2 low (IHC 1+ and IHC 2+/ISH-) |
Overall trial population (HER2 low and HER2 ultralow) |
HER2 ultralow (defined as IHC 0 with membrane staining)i,ii |
|||
ENHERTU (n=359) |
Chemotherapy (n=354) |
ENHERTU (n=436) |
Chemotherapy (n=430) |
ENHERTU (n=76) |
Chemotherapy (n=76) |
|
PFS |
||||||
Median PFSiii (months)
( |
13.2 months |
8.1 months |
13.2 months |
8.1 months |
13.2 months |
8.3 months |
HR ( |
0.62 (0.51-0.74) |
0.63 (0.53-0.75) |
0.78 (0.50-1.21) |
|||
p-value |
p<0.0001 |
p<0.0001 |
--- |
|||
OS |
||||||
12 month OS Rate (%)
( |
|
|
|
|
|
|
HR ( |
0.83 (0.66-1.05) |
0.81 (0.65-1.00)v |
0.75 (0.43-1.29) |
|||
p-value |
p=0.1181vi |
--- |
--- |
|||
ORR |
||||||
Confirmed ORRi,iii,vii (%) (n) |
|
|
|
|
|
|
Best Overall Response |
||||||
CR % (n) |
|
0 |
|
0 |
|
0 |
PR % (n) |
|
|
|
|
|
|
SD % (n) |
|
|
|
|
|
|
Median DOR (months) |
14.1 months |
8.6 months |
14.3 months |
8.6 months |
14.3 months |
14.1 months |
CI, confidence interval; CR, complete response; DOR, duration of response; HR, hazard ratio; NA, not available; PFS, progression-free survival; ORR, objective response rate; OS, overall survival; PR, partial response; SD, stable disease i Descriptive analysis ii Per central lab iii As assessed by BICR
iv Less than v No test of significance was performed in line with the multiple testing procedure vi P-value of 0.0046 required for statistical significance at this OS interim analysis vii ORR is (CR + PR) |
Additional ENHERTU Data at ASCO
DESTINY-Breast03 Updated Results
Updated overall survival (OS) results from the DESTINY-Breast03 phase 3 trial also presented as a poster show ENHERTU continued to demonstrate a clinically meaningful survival improvement over trastuzumab emtansine (T-DM1) after more than three years of follow-up in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab. In the updated analysis of OS, the key secondary endpoint of median OS has been reached in both treatment arms. Median OS was 52.6 months (
The safety profile of ENHERTU continues to be generally manageable and no cumulative toxicities were observed with longer follow-up. Grade 3 or higher treatment related TEAEs occurred in
DESTINY-Breast07 Results
Interim results from the DESTINY-Breast07 phase 1b/2 trial of ENHERTU alone or in combination with other anticancer therapies as a first-line treatment for HER2 positive metastatic breast cancer also were presented as an oral presentation. In the analysis, ENHERTU demonstrated promising activity as a monotherapy (n=75) and in combination with pertuzumab (n=50).
Confirmed ORR in the ENHERTU monotherapy arm was
The safety of ENHERTU as a monotherapy and in combination with pertuzumab was consistent with known safety profiles of each therapy. Grade 3 or higher TEAEs occurred in
This is the first dataset of ENHERTU as a first-line treatment of HER2 positive metastatic breast cancer. Analyses from the ongoing DESTINY-Breast09 phase 3 trial will provide further insights regarding the efficacy and safety of ENHERTU in this HER2 positive patient population.
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.
The primary endpoint 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) at multiple sites in
About DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
The primary efficacy endpoint of DESTINY-Breast03 is PFS based on BICR. OS is the key secondary efficacy outcome measure. Other secondary endpoints include ORR, DOR, PFS based on investigator assessment and safety.
DESTINY-Breast03 enrolled 524 patients at multiple sites in
About DESTINY-Breast07
DESTINY-Breast07 is a global, randomized, open-label phase 1b/2 dose-finding and dose-expansion trial to explore the safety, tolerability and antitumor activity of ENHERTU alone or in combination with other anticancer agents in patients with HER2 positive metastatic breast cancer. The study consists of two phases: a dose escalation phase and a dose expansion phase. The dose escalation phase enrolled patients with locally assessed HER2 positive or advanced metastatic breast cancer in second-line or later treatment. The dose expansion phase enrolled patients with locally assessed HER2 positive breast cancer previously untreated for advanced or metastatic disease.
The primary endpoints of DESTINY-Breast07 are safety and tolerability. Secondary endpoints include ORR and PFS based on investigator assessment.
DESTINY-Breast07 enrolled 244 patients at multiple sites 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 While survival rates are high for those diagnosed with early breast cancer, only about
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer.3 Patients with high levels of HER2 expression (IHC 3+ or IHC2+/ISH+) are classified as HER2 positive and treated with HER2 targeted therapies, representing approximately 15 to
Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer. However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited. 8 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 8,9,10,11
Prior to the approval of ENHERTU following chemotherapy in HER2 low metastatic breast cancer based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2 low expression.12 There are no targeted therapies specifically approved for patients with HER2 ultralow expression.13
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the
ENHERTU (5.4 mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (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 60 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 more than 35 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 trial. Continued approval in the
ENHERTU (6.4 mg/kg) is approved in more than 45 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 and/or DESTINY-Gastric02 trials.
ENHERTU (5.4 mg/kg) is approved in the
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 datopotamab deruxtecan in July 2020, except in
About the DXd ADC Portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, 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.,
Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, 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.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 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 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 (IHC3+) 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 |
|
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.
HER2-Positive or HER2-Low 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 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.
HER2-Positive or HER2-Low 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 or HER2-Low 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 one level.
Adverse Reactions
HER2-Positive and HER2-Low 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 1799 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, 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 one dose of ENHERTU 5.4 mg/kg intravenously once every three weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30).
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
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
ENHERTU was permanently discontinued in
The most common (≥
HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)
DESTINY-Lung02 evaluated two 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 three 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 one 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 (IHC3+) Unresectable or Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC3+) 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.
-
Geriatric Use: Of the 1287 patients with HER2-positive or HER2-low breast cancer treated with ENHERTU 5.4 mg/kg,
22% were ≥65 years and3.8% 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% ). 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 or older and9% were 75 years or older. 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.
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References
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13 Eiger D, et al. Cancers. 2021 Mar; 13(5): 1015.
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Global/US:
Jennifer Brennan
Daiichi Sankyo, Inc.
jbrennan2@dsi.com
+1 908 900 3183 (mobile)
Daiichi Sankyo Co., Ltd.
DS-PR@daiichisankyo.co.jp
Investor Relations Contact:
DaiichiSankyoIR@daiichisankyo.co.jp
Source: Daiichi Sankyo, Inc.
FAQ
What is the progression-free survival for ENHERTU in HR positive, HER2 low and ultralow metastatic breast cancer?
How does ENHERTU compare to chemotherapy in terms of disease progression in the DESTINY-Breast06 trial?
What was the overall response rate (ORR) for ENHERTU in the trial?
What were the significant adverse events reported for ENHERTU in the DESTINY-Breast06 trial?