ENHERTU® Additional Analyses Further Reinforce Groundbreaking Efficacy in Patients with HER2 Positive Metastatic Breast Cancer
The DESTINY-Breast03 phase 3 trial results presented at SABCS 2021 show that ENHERTU (trastuzumab deruxtecan) significantly outperforms T-DM1 in treating HER2 positive metastatic breast cancer. ENHERTU demonstrated higher progression-free survival (PFS) and objective response rate (ORR), particularly in patients with stable brain metastases. Notably, PFS for these patients was 15 months for ENHERTU compared to just 3 months for T-DM1. The safety profile remains consistent, with a low incidence of severe adverse events. These findings suggest ENHERTU's potential as a new standard of care.
- ENHERTU showed higher PFS (15 months) compared to T-DM1 (3 months) in patients with stable brain metastases.
- Overall ORR for ENHERTU was 67.4% versus 20.5% for T-DM1 in the same subgroup.
- Significant reduction in progression or death risk (72%) compared to T-DM1 (HR=0.28).
- Safety profile consistent with prior studies; no new safety concerns identified.
- None.
- DESTINY-Breast03 data presented at SABCS 2021 showed Daiichi Sankyo and AstraZeneca’s ENHERTU demonstrated a similar benefit in patient subgroups, including those with stable brain metastases, compared to T-DM1
A similar PFS and ORR benefit was observed in exploratory analyses in patients defined by presence of stable brain metastases, hormone receptor status, number of prior lines of therapy, prior treatment with pertuzumab or status of visceral metastasis. In patients with stable brain metastases at baseline, treatment with ENHERTU resulted in higher PFS compared to T-DM1 (n=82; PFS by blinded independent central review [BICR], hazard ratio [HR] = 0.25;
“The main goals in the treatment of HER2 positive metastatic breast cancer, including those with stable brain metastases, are to improve symptoms, stabilize or reduce the tumor size and improve overall survival,” said
Confirmed ORR for patients with stable brain metastases at baseline (n=82) was
The safety profile of the most common adverse events with ENHERTU in DESTINY-Breast03 remains consistent with previous clinical trials of ENHERTU in breast cancer with no new safety concerns identified. The most common grade 3 or higher treatment emergent adverse events were neutropenia (
“These additional analyses from DESTINY-Breast03 continue to demonstrate the benefit of ENHERTU compared to T-DM1 in patient subgroups, including 15 month progression-free survival in those with stable brain metastases, illustrating the potential of this treatment to become the new standard of care in patients with previously treated HER2 positive metastatic breast cancer,” said
“More treatment options are needed to delay progression and extend survival for patients with HER2 positive metastatic breast cancer who develop brain metastases,” said
Summary of DESTINY-Breast03 Subgroup Analyses
|
Median PFS by BICR ( |
ORR % ( |
||
|
ENHERTU |
T-DM1 |
ENHERTU |
T-DM1 |
All Patients (n=524) |
NE (18.5-NE) |
6.8 (5.6-8.2) |
79.7 |
34.2 |
|
HR=0.2840 (0.2165-0.3727) |
45.5 (37.6-53.4)a |
||
Hormone Receptor |
||||
Positive (n=272) |
22.4 (17.7-NE) |
6.9 (4.2-9.8) |
78.2 |
30.9 |
|
HR=0.3191 (0.2217-0.4594) |
47.3 (36.1-58.4)a |
||
Negative (n=248) |
NE (18.0-NE) |
6.8 (5.4-8.3) |
81.7 |
38.5 |
|
HR=0.2965 (0.2008-0.4378) |
43.2 (31.5-55.0)a |
||
Prior Pertuzumab |
||||
Yes (n=320) |
NE (18.5-NE) |
6.8 (5.4-8.3) |
79.6 |
32.9 |
|
HR=0.3050 (0.2185-0.4257) |
46.7 (36.5-56.9)a |
||
No (n=204) |
NE (16.5-NE) |
7.0 (4.2-9.7) |
79.8 |
36.2 |
|
HR=0.2999 (0.1924-0.4675) |
43.6 (30.5-56.7)a |
||
Visceral Disease |
||||
Yes (n=384) |
22.2 (16.5-NE) |
5.7 (4.2-7.0) |
77.4 |
29.1 |
|
HR=0.2806 (0.2083-0.3779) |
48.3 (39.1-57.6)a |
||
No (n=140) |
NE (NE-NE) |
11.3 (6.8-NE) |
86.4 |
47.3 |
|
HR=0.3157 (0.1718-0.5804) |
39.1 (23.6-54.6)a |
||
|
||||
0-1 (n=258) |
22.4 (17.9-NE) |
8.0 (5.7-9.7) |
75.0 |
35.7 |
|
HR=0.3302 (0.2275-0.4794) |
39.3 (27.3-51.2)a |
||
≥2 (n=266) |
NE (16.8-NE) |
5.6 (4.2-7.1) |
84.5 |
32.8 |
|
HR=0.2828 (0.1933-0.4136) |
51.6 (40.9-62.4)a |
||
Patients with Stable Brain Metastases at Baseline |
||||
Yes (n=82) |
15.0 (12.5-22.2) |
3.0 (2.8-5.8) |
67.4 |
20.5 |
|
HR=0.2465 (0.1341-0.4529) |
46.9 (25.6-68.3)a |
||
No (n=442) |
NE (22.4-NE) |
7.1 (5.6-9.7) |
82.1 |
36.6 |
|
HR=0.2971 (0.2199-0.4014) |
45.5 (36.9-54.1)a |
||
CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; NE, not estimable; ORR, objective response rate
|
||||
All patients in DESTINY-Breast03 received at least one prior cancer therapy, including trastuzumab (ENHERTU =
Based on the primary results of DESTINY-Breast03, ENHERTU received its fourth Breakthrough Therapy Designation (BTD) in the
About DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the safety and efficacy 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. Secondary efficacy endpoints include overall survival, ORR, duration of response, PFS based on investigator assessment and safety. DESTINY-Breast03 enrolled 524 patients at multiple sites in
About HER2 Positive Breast Cancer
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million cases of breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 Approximately one in five cases of breast cancer are considered HER2 positive.2
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.4
Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.5 Additionally, it is estimated that
About ENHERTU
ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the
ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens based on the results from the DESTINY-Breast01 trial.
ENHERTU (6.4 mg/kg) is also approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
A Type II Variation is currently under review by the
ENHERTU is approved in the
About the ENHERTU Clinical Development Program
A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
ENHERTU was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the “ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers,” based on data from both the DESTINY-Gastric01 and DESTINY-CRC01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC) based on the interim results of the HER2 mutated cohort of the DESTINY-Lung01 trial.
In
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
-
Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.
This indication is approved under accelerated approval based on tumor 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 gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
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. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.
Metastatic Breast Cancer
In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in
Locally Advanced or Metastatic Gastric Cancer
In DESTINY-Gastric01, of the 125 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. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.
Metastatic Breast Cancer
In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4mg/kg, a decrease in neutrophil count was reported in
Locally Advanced or Metastatic Gastric Cancer
In DESTINY-Gastric01, of the 125 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. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (
Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. When LVEF is >
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 at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 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. Reduce dose by one level.
Adverse Reactions
Metastatic Breast Cancer
The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).
Serious adverse reactions occurred in
ENHERTU was permanently discontinued in
The most common (≥
Locally Advanced or Metastatic Gastric Cancer
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.
Serious adverse reactions occurred in
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 following 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 at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following 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 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg,
26% were ≥65 years and5% were ≥75 years. No overall differences in efficacy 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 (53% ) as compared to younger patients (42% ). Of the 125 patients with locally advanced or metastatic HER2‑positive 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. - Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.
To report SUSPECTED ADVERSE REACTIONS, contact
Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
About Daiichi Sankyo in Oncology
The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd ADC technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in
About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the
References
_________________
1 Sung H, et al. CA Cancer J Clin. 2021;10.3322/caac.21660.
2 Ahn S, et al. J Pathol Transl Med. 2020;54(1): 34–44.
3 Iqbal N, et al. Mol Biol Int. 2014;852748.
4 Pillai R, et al. Cancer. 2017;1;123(21):4099-4105.
5 Barok M, et al. Breast Cancer Res. 2014; 16(2):209.
6 Mounsey L, et al.
7 Martínez-Sáez O, Prat A. JCO Oncol Pract. 2021. 10.1200/OP.21.00172.
8 Verma S, et al. N Engl J Med. 2012;367:1783-1791.
9 Garcia-Alvarez, A et al. Cancers. 2021; 13(12):2927.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211209005303/en/
Media:
Global:
vamari@dsi.com
+1 908 900 3010 (mobile)
US:
domurphy@dsi.com
+1 917 817 2649 (mobile)
EU:
lydia.worms@daiichi-sankyo.eu
+49 (89) 7808751 (office)
+49 176 11780861 (mobile)
Daiichi Sankyo Co., Ltd.
kawase.masashi.a2@daiichisankyo.co.jp
+81 3 6225 1126 (office)
Investor Relations:
DaiichiSankyoIR@daiichisankyo.co.jp
Source: Daiichi Sankyo
FAQ
What were the results of the DESTINY-Breast03 trial for AZN?
How did ENHERTU perform against T-DM1 in patients with stable brain metastases?
What is the significance of the DESTINY-Breast03 trial results for AZN?
What is the safety profile of ENHERTU based on DESTINY-Breast03 data?
What is the hazard ratio for disease progression or death with ENHERTU compared to T-DM1?
