^
Association details:
| Biomarker: | HER-2 positive |
|---|---|
| Cancer: | HER2 Positive Breast Cancer |
| Drug: | Enhertu (fam-trastuzumab deruxtecan-nxki) (Topoisomerase I inhibitor, HER2-targeted antibody-drug conjugate) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
NHS Scotland Grants Trastuzmab Deruxtecan Approval for Use in Pretreated HER2+ Metastatic Breast Cancer
Published date:
04/12/2023
Excerpt:
The Scottish Medicines Consortium (SMC) has accepted fam-trastuzumab deruxtecan-nxki (Enhertu) as a treatment option for adult patients with HER2-positive unresectable or metastatic breast cancer who have received 1 prior anti–HER2-based therapy....The advice is based on findings from the pivotal phase 3 DESTINY-Breast03 trial (NCT03529110), in which trastuzumab deruxtecan led to a 12-month progression-free survival (PFS) rate of 75.8%...
Source:
Title:
Enhertu approved in China for patients with HER2-positive metastatic breast cancer treated with one or more prior anti-HER2-based regimens
Published date:
02/24/2023
Excerpt:
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in China as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens....The approval by China’s National Medical Products Administration (NMPA) is based on the results of the DESTINY-Breast03 Phase III trial, where Enhertu demonstrated a 72% reduction in the risk of disease progression or death compared to trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p<0.000001) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
Source:
Title:
ENHERTU® Approved in Japan for Patients with Previously Treated HER2 Positive Metastatic Breast Cancer
Published date:
11/24/2022
Excerpt:
Daiichi Sankyo...announced that ENHERTU® (trastuzumab deruxtecan) has been approved in Japan for the treatment of adult patients with HER2 positive unresectable or recurrent breast cancer after prior chemotherapy, which includes trastuzumab and a taxane....The approval by Japan’s Ministry of Health, Labour and Welfare (MHLW) was based on the results of the DESTINY-Breast03 trial where ENHERTU demonstrated a 72% reduction in the risk of disease progression or death compared to trastuzumab emtansine (T-DM1) (hazard ratio [HR] = 0.28; 95% confidence interval [CI]: 0.22-0.37; p<0.000001) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
Source:
Title:
Domestic approval of Enhertu opens new ways to treat breast and stomach cancer
Published date:
09/20/2022
Excerpt:
Enhertu, a new breast and stomach cancer treatment, has won domestic approval...The domestic approval of Enhertu aims to treat non-abstractable or metastatic HER2-positive breast cancer patients with two or more administrations of HER2-based treatments, and locally progressive or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma patients with two or more administrations of treatments, including anti-HER2 treatment.
Source:
Title:
Enhertu approved in the EU for patients with HER2-positive metastatic breast cancer treated with one or more prior anti-HER2-based regimens
Published date:
07/19/2022
Excerpt:
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens....Based on ground-breaking DESTINY-Breast03 results in which Enhertu demonstrated a 72% reduction in the risk of disease progression or death vs. trastuzumab emtansine (T-DM1).
Source:
Published date:
05/04/2022
Excerpt:
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 a prior anti-HER2-based regimen...
Source:
Title:
ENHERTU (TRASTUZUMAB DERUXTECAN) AUTHORISED IN THE UK FOR THE TREATMENT OF HER2 POSITIVE METASTATIC BREAST CANCER
Published date:
02/16/2021
Excerpt:
Daiichi Sankyo...and AstraZeneca UK’s Enhertu (trastuzumab deruxtecan) has been granted conditional authorisation in the UK as a monotherapy 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.
Source:
Published date:
01/18/2021
Excerpt:
Enhertu as monotherapy is 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.
Source:
Title:
Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Guideline Update
Published date:
05/31/2022
Excerpt:
Recommendation...If a patient's HER2-positive advanced breast cancer has progressed during or after first-line HER2-targeted therapy (and the patient has not received trastuzumab deruxtecan [T-Dxd]), clinicians should recommend T-Dxd as a second-line treatment...
DOI:
10.1200/JCO.22.00519
Source:
Title:
Trastuzumab deruxtecan for treating HER2-positive unresectable or metastatic breast cancer after 2 or more anti-HER2 therapies
Published date:
05/26/2021
Excerpt:
Trastuzumab deruxtecan is recommended for use within the Cancer Drugs Fund as an option for treating HER2‑positive unresectable or metastatic breast cancer in adults after 2 or more anti‑HER2 therapies.
Source:
Published date:
07/15/2020
Excerpt:
...fam-trastuzumab deruxtecan-nxki has been added to other recommended regimens for HER-2 positive recurrent or stage IV (M1) disease.
Source:
Title:
ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer
Excerpt:
HER2-positive breast cancer...Recommendations...Second-line treatment...Trastuzumab deruxtecan should be given as second-line therapy after progression on a taxane and trastuzumab
DOI:
https://doi.org/10.1016/j.annonc.2021.09.019.
Source:
Title:
Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial
Published date:
05/27/2023
Excerpt:
Median progression-free survival by blinded independent central review was 17·8 months (95% CI 14·3-20·8) in the trastuzumab deruxtecan group versus 6·9 months (5·5-8·4) in the treatment of physician's choice group (HR 0·36 [0·28-0·45]; p<0·0001)….DESTINY-Breast02 shows the favourable benefit-risk profile of trastuzumab deruxtecan in patients with HER2 positive metastatic breast cancer, as previously reported in DESTINY-Breast01, and is the first randomised study to show that one antibody-drug conjugate can overcome resistance to a previous one.
Secondary therapy:
capecitabine
DOI:
https://doi.org/10.1016/S0140-6736(23)00725-0
Trial ID:
Source:
Title:
Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial
Published date:
12/07/2022
Excerpt:
Trastuzumab deruxtecan showed a significant improvement in overall survival versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer, as well as the longest reported median progression-free survival, reaffirming trastuzumab deruxtecan as the standard of care in the second-line setting.
DOI:
10.1016/S0140-6736(22)02420-5
Source:
Title:
236P - Subgroup analysis by disease history and prior treatments of patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC) from DESTINY-Breast03, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1)
Published date:
09/05/2022
Excerpt:
Pts with HER2+ MBC whose disease had progressed on or after trastuzumab and a taxane were randomized 1:1 to receive T-DXd or T-DM1….Confirmed objective response rates were consistent between de novo (T-DXd, 79.6% [95% CI, 69.9-87.2] vs T-DM1, 33.7% [24.7-43.6]) and recurrent (T-DXd, 79.8% [72.9-85.6] vs T-DM1, 34.6% [27.2-42.5]) MBC....In this exploratory analysis, a benefit of T-DXd vs T-DM1 was observed irrespective of disease history and prior treatment, consistent with the results of the overall primary analysis.
Trial ID:
Source:
Title:
Enhertu significantly delayed disease progression in DESTINY-Breast02 Phase III trial vs. physician’s choice of treatment in patients with HER2-positive metastatic breast cancer
Published date:
08/15/2022
Excerpt:
Positive high-level results from the DESTINY-Breast02 Phase III trial of Enhertu (trastuzumab deruxtecan) versus physician’s choice of treatment showed the trial met the primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1).
Secondary therapy:
capecitabine
Trial ID:
Source:
Title:
Trastuzumab Deruxtecan Recommended for Approval in the EU by CHMP for Patients with HER2 Positive Metastatic Breast Cancer Treated with a Prior Anti-HER2-Based Regimen
Published date:
06/27/2022
Excerpt:
Trastuzumab Deruxtecan Recommended for Approval in the EU by CHMP for Patients with HER2 Positive Metastatic Breast Cancer Treated with a Prior Anti-HER2-Based Regimen...The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the DESTINY-Breast03 phase 3 trial...
Source:
Title:
Trastuzumab Deruxtecan Improves Progression-Free Survival and Intracranial Response in Patients with HER2-Positive Metastatic Breast Cancer and Brain Metastases
Published date:
03/28/2022
Excerpt:
In the phase III DESTINY-Breast03 trial, trastuzumab deruxtecan improved progression-free survival (PFS) relative to trastuzumab emtansine across all patients with HER2-positive metastatic breast cancer, including a 75% improvement in PFS among those with baseline brain metastases.
DOI:
10.1093/oncolo/oyac009
Trial ID:
Source:
Title:
Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer
Published date:
03/24/2022
Excerpt:
An overall response (a complete or partial response) occurred in 79.7% (95% CI, 74.3 to 84.4) of the patients who received trastuzumab deruxtecan and in 34.2% (95% CI, 28.5 to 40.3) of those who received trastuzumab emtansine….Among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, the risk of disease progression or death was lower among those who received trastuzumab deruxtecan than among those who received trastuzumab emtansine.
DOI:
10.1056/NEJMoa2115022
Trial ID:
Source:
Title:
ENHERTU® Granted Priority Review in the U.S. for Patients with HER2 Positive Metastatic Breast Cancer Treated with a Prior Anti-HER2-Based Regimen
Published date:
01/17/2022
Excerpt:
Daiichi Sankyo Company...and AstraZeneca (LSE/STO/Nasdaq: AZN) have received notification of acceptance by the U.S. Food and Drug Administration (FDA) of the supplemental Biologics License Application (sBLA) of ENHERTU® (fam-trastuzumab deruxtecan-nxki) for the treatment of adult patients in the U.S. with unresectable or metastatic HER2 positive breast cancer who have received a prior anti-HER2-based regimen....The sBLA is based on data from the pivotal DESTINY-Breast03 phase 3 trial that were presented at the 2021 European Society for Medical Oncology (ESMO) Congress.
Source:
Title:
Trastuzumab deruxtecan (T-DXd; DS-8201a) vs. trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): subgroup analyses from the randomized phase 3 study DESTINYBreast03
Published date:
10/09/2021
Excerpt:
Overall, confirmed ORR for T-DXd was 79.7% vs. 34.2% for T-DM1...For patients with stable BMs at baseline, ORR was 67.4% for T-DXd vs. 20.5% forT-DM1. Consistent PFS and ORR benefit was also observed across other subgroups...Overall, the safety profile of T-DXd was manageable and comparable with its known safety profile...In this exploratory analysis, consistent PFS and ORR benefit with T-DXd vs. T-DM1 was observed across subgroups in pts with HER2+ mBC previously treated with trastuzumab...
Source:
Title:
Based on ground-breaking DESTINY-Breast03 results where Enhertu reduced the risk of disease progression or death by 72% vs. trastuzumab emtansine (T-DM1)
Published date:
10/04/2021
Excerpt:
The Food and Drug Administration (FDA) has granted Enhertu (trastuzumab deruxtecan), Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens.
Trial ID:
Source:
Title:
LBA1 - Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study
Published date:
09/13/2021
Excerpt:
This is the first report of DESTINY-Breast03 (NCT03529110), a multicenter, open-label, randomized phase 3 study comparing the efficacy and safety of T-DXd vs T-DM1 in pts with HER2+ mBC...The estimated 12-month OS event rates were 94.1% (95% CI, 90.3-96.4) for T-DXd and 85.9% (95% CI, 80.9-89.7) for T-DM1; HR: 0.5546 (95% CI, 0.3587-0.8576; P = 0.007172...T-DXd demonstrated a highly statistically significant and clinically meaningful improvement in PFS vs T-DM1 in pts previously treated with trastuzumab and taxane for HER2+ mBC.
Trial ID:
Source:
Title:
LBA1 - Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study
Published date:
09/13/2021
Excerpt:
T-DXd demonstrated a highly statistically significant and clinically meaningful improvement in PFS vs T-DM1 in pts previously treated with trastuzumab and taxane for HER2+ mBC.
Trial ID:
Source:
Title:
Enhertu significantly improved progression-free survival in DESTINY-Breast03 head-to-head trial vs. trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer
Published date:
08/09/2021
Excerpt:
DESTINY-Breast03 met the primary endpoint of progression-free survival (PFS) showing a highly statistically significant and clinically meaningful improvement for patients with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane...Enhertu also showed a strong trend toward improved overall survival (OS) compared to T-DM1 in a key secondary endpoint...
Trial ID:
Source:
Title:
EMA Validates and Grants Accelerated Assessment for Trastuzumab Deruxtecan for the Treatment of HER2 Positive Metastatic Breast Canc
Published date:
07/26/2020
Excerpt:
Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for trastuzumab deruxtecan, a HER2 directed antibody drug conjugate (ADC), for the treatment of adults with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens.
Source:
Title:
DS-8201a in Patients With Cancer That Tests Positive for Human Epidermal Growth Factor Receptor 2 (HER2) Protein
Excerpt:
...Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)`Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)`Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)`Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)`Best Overall Response By The Investigator's Assessment (Unconfirmed) in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer`Objective Response Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer`Disease Control Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer...
Trial ID:
Source:
Title:
Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)
Excerpt:
...is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+) 3....
More C2 evidence
Source:
Title:
Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer
Excerpt:
...- Histologically documented HER2-positive early breast cancer (EBC) participants, including clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or ≥ T3, N0, M0 as determined by the AJCC staging system, 8th edition...
Trial ID:
Source:
Title:
A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer
Excerpt:
...HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment....
Trial ID:
Source:
Title:
Testing the Biological Effects of DS-8201a on Patients With Advanced Cancer
Excerpt:
...- Patients must have HER2-positive or HER2-expressing tumors as defined by Clinical Laboratory Improvement Act (CLIA)-certified labs....
Trial ID:
Source:
Title:
DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer
Excerpt:
...- Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-positive expression as per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) Guidelines...
Trial ID:
Source:
Title:
Basket Study for Oligo-metastatic Breast Cancer
Excerpt:
...- Histologic proof of infiltrating HER2-positive breast cancer (as determined by IHC 3+ and/or amplification by ISH)[8]...
Trial ID:
Source:
Title:
An Observational Study of Patients Receiving T-DXd for Treatment of HER2+, and HER2-low Unresectable and/or Metastatic Breast Cancer
Excerpt:
...- Documented HER2-positive status via a validated method on the most recent sample tested in or closest to the metastatic setting as available....
Trial ID:
Source:
Title:
A Study to Assess the Effectiveness of Trastuzumab Deruxtecan in Chinese Breast Cancer Patients (REFRESH)
Excerpt:
...Real World Time to Next Treatment (rwTTNT) in Participants With HER2-positive and HER2-low Unresectable or Metastatic Breast Cancer...
Trial ID:
Source:
Title:
Trastuzumab Deruxtecan (T-DXd): Tailoring Treatment and Companion Diagnostics (CDx) by Liquid Biopsy
Excerpt:
...- Subjects must have confirmed, per local testing on most recent tumor tissue sample available, an HER2-positive expression, as determined according to American Society of Clinical Oncology...
Trial ID:
Source:
Title:
Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]
Excerpt:
...Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines)...
Trial ID:
Source:
Title:
DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02]
Excerpt:
...has confirmed HER2-positive expression as determined according to American Society of Clinical Oncology...
Trial ID:
Source:
Title:
EUropean Real-world Experience Of Previously Treated Advanced/Metastatic HER2-positive Breast Cancer Patients Accessing Trastuzumab Deruxtecan
Excerpt:
...- Participants for whom T-DXd treatment is indicated, according to the summary of product characteristics conditionally approved by the EMA, that are eligible for treatment with T-DXd through the NPP (i.e., those with advanced/metastatic HER2+ breast cancer who have received ≥ 2 prior anti-HER2-based regimens and have documentation of HER2 positive tumour status by a validated method) will be eligible for inclusion to this RWD collection, subject to providing written informed consent to participate....
Trial ID:
Source:
Title:
A Study of T-DXd in Participants With or Without Brain Metastasis Who Have Previously Treated Advanced or Metastatic HER2 Positive Breast Cancer
Excerpt:
...unresectable/advanced or metastatic; confirmed HER2-positive status expression as determined according to American Society of Clinical Oncology/College of American Pathologists guidelines -...
Trial ID:
Source:
Title:
Study of DS-8201a in Subjects With Advanced Solid Malignant Tumors
Excerpt:
...HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer....
Trial ID:
Source:
Title:
A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)
Excerpt:
...- Pathologically documented HER2-positive breast cancer (BC):...
Trial ID:
Source:
Title:
Neoadjuvant Trastuzumab Deruxtecan (T-DXd) With Response-directed Definitive Therapy in Early Stage HER2-positive Breast Cancer (SHAMROCK Study)
Excerpt:
...Histologically confirmed HER2-positive breast cancer: o Documented HER2 overexpression by local laboratory (IHC 3+ or FISH or CISH positive on diagnostic breast biopsy)....
Trial ID:
Source:
Title:
A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1)
Excerpt:
...has HER2 positive expression confirmed per protocol...
Trial ID:
Source:
Title:
DS-8201a for trEatment of aBc, BRain Mets, And Her2[+] Disease
Excerpt:
...HER2 positive status...
Trial ID:
Source:
Title:
A phase 2 clinical trial conducted investigate the effectiveness of trastuzumab deruxtecan (T-DXd) administered before surgery for the treatment of HER-2 positive breast cancer.
Excerpt:
...Histologically confirmed HER2-positive breast cancer:o Documented HER2 overexpression by local laboratory (IHC 3+ or FISH or CISH positive on diagnostic breast biopsy).3. ...
Trial ID:
Source:
Title:
DESTINY-Breast11 will compare trastuzumab deruxtecan (T-DXd) alone or in sequence with other medications, known as THP, with standard of care treatment (ddAC-THP) and determine its safety and efficacy in patients with HER2-positive early breast cancer. Lo studio DESTINY-Breast11 confronterà trastuzumab deruxtecan (T-DXd) usato singolarmente o in sequenza con altri farmaci noti come THP, con la terapia standard ddAC-THP) e determinerà la sua sicurezza ed efficacia in pazienti con carcinoma mammario HER2-positivo in stadio precoce.
Excerpt:
...- Patients must be at least 18 years of age.- Histologically documented HER2-positive EBC participants with:(a) locally assessed HER2-positive (IHC 3+ or ISH+) according to ASCOCAP guidelines and prospectively centrally confirmed as HER2 positivebased on a tumour sample (b) unifocal and multifocal tumours (> 1 tumour confined to the same quadrant as the primary tumour) must have 1 focus sampled and centrally confirmed as HER2 positive(c) multi-centric tumours (multiple tumours involving > 1 quadrant of the breast) must have 1 lesion from each involved quadrant sampled and centrally confirmed as HER2 positive. ...
Trial ID:
Source:
Title:
Clinical trial comparing Trastuzumab Deruxtecan with Trastuzumab Emtansine in high-risk HER2-positive patients with residual breast cancer following neoadjuvant therapy
Excerpt:
...HER2-positive breast cancer, meeting all of the criteria listed in the protocol (see protocol for full details). ...
Trial ID:
Source:
Title:
A study to investigate the efficacy and safety of trastuzumab deruxtecan in patients With or Without Brain Metastasis Who Have Previously-Treated Advanced or Metastatic HER2 Positive Breast Cancer
Excerpt:
...Pathologically documented breast cancer that: (a) Is unresectable/advanced or metastatic, and (b) Has confirmed HER2-positive status as determined according to ASCO/CAP guidelines (Wolff et al, 2018) evaluated at a local laboratory2. ...
Trial ID:
Source:
Title:
DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]
Excerpt:
...has confirmed HER2-positive expression as determined according to American Society of Clinical Oncology...
Trial ID:
Source:
Title:
A Phase II Study of T-DXd Plus SRT in HER2-positive Breast Cancer Brain Metastases
Excerpt:
...- Pathologically confirmed HER2 positive advanced breast cancer...
Trial ID:
Less C2 evidence
Source:
Title:
Trastuzumab Deruxtecan in Previously Treated Patients With HER2-Positive Metastatic Breast Cancer: Updated Survival Results From a Phase 2 Trial (DESTINY-Breast01)
Published date:
12/11/2023
Excerpt:
The objective response rate by independent central review was 62.0% (95% CI, 54.5-69.0) in patients who received T-DXd 5.4 mg/kg every 3 weeks (n = 184). Median overall survival was 29.1 months (95% CI, 24.6-36.1). Median progression-free survival and duration of response were 19.4 months (95% CI, 14.1-25.0) and 18.2 months (95% CI, 15.0 months-not evaluable), respectively....These updated results provide further evidence of sustained antitumor activity of T-DXd with a consistent safety profile in heavily pretreated patients with HER2-positive mBC.
DOI:
10.1016/j.annonc.2023.12.001
Source:
Title:
FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES
Published date:
12/02/2023
Excerpt:
At 26.5 months median follow-up, median PFS was 21 months...In TUXEDO-1, T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive breast cancer BM.
Source:
Title:
Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM)
Published date:
12/02/2023
Excerpt:
Subgroup analyses showed that median OS in pts with active BM was 27.0 months (95% CI, 16.4 to NR) and that median OS was NR in pts with stable BM or LMC (2-year OS rate for pts with stable BM, 71.6%; 2-year OS rate for pts with LMC, 61.6%)….The updated OS results of this retrospective chart review show that T-DXd has promising effectiveness in HER2+ MBC pts with long-term and heavily pretreated BM and LMC.
Source:
Title:
Trastuzumab Deruxtecan in patients with HER2[+] or HER2-Low Advanced Breast Cancer and Pathologically Confirmed Leptomeningeal Carcinomatosis: Results from Cohort 5 of the DEBBRAH Study
Published date:
12/02/2023
Excerpt:
Median OS rate was 13.3 months (95% CI, 5.7-NA, p< 0.001) meeting the primary endpoint….T-DXd showed promising activity with no new safety concerns in HER2[+] and HER2-low pts with previously untreated, pathologically confirmed LMC.
Trial ID:
Source:
Title:
A comparison of the efficacy of trastuzumab deruxtecan in advanced HER2-positive breast cancer: active brain metastasis versus progressive extracranial disease alone
Published date:
12/02/2023
Excerpt:
We demonstrate that in advanced HER2 positive breast cancer that T-DXd is as effective, in terms of PFS and OS, in active BMs as it is in progressive extracranial disease alone. These data provide the first evidence that in contrast to the historical data that active BM may no longer be a detriment to survival as compared to progressive extracranial disease alone when treated with T-Dxd.
Source:
Title:
Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study
Published date:
11/23/2023
Excerpt:
With a median follow-up of 12 months, the median rwPFS was 16 months. RwPFS was 84%, 59%, and 39% at 6, 12, and 18 months, respectively….Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HER2+ mBC. These results are consistent with the results of known findings, and no new safety concerns were reported.
DOI:
https://doi.org/10.1093/oncolo/oyad308
Source:
Title:
414P - Trastuzumab deruxtecan for HER2-positive breast cancer brain metastasis: A systematic review and meta-analysis
Published date:
10/16/2023
Excerpt:
The objective response rate (ORR) was 61% (95% CI 53-68%), and the intracranial (IC)-ORR was 62% (95% CI 55-70%)….Our systematic review and meta-analysis supports the intracranial activity of T-DXd in both patients with stable BM and active BM. HER2-positive BCBM patients treated with T-DXd achieved ORR and IC-ORR higher than 50% in the clinical trials setting and in real-world data.
Source:
Title:
Treatment with trastuzumab deruxtecan in patients with HER2-positive breast cancer and brain metastases and/or leptomeningeal disease (ROSET-BM)
Published date:
10/11/2023
Excerpt:
This was a study of 104 HER2-positive breast cancer patients with BM who were treated with T-DXd in a real-world clinical setting....Median PFS was 16.1 months; 12-month OS rate was 74.9% (total population). Median time-to-treatment failure was 9.7 months….T-DXd showed effectiveness regarding IC-ORR, IC-PFS, PFS, and OS in breast cancer patients with BM/active BM...
DOI:
10.1038/s41523-023-00584-5
Source:
Title:
Efficacy and safety of trastuzumab deruxtecan in the treatment of HER2-low/positive advanced breast cancer: a single-arm meta-analysis
Published date:
06/22/2023
Excerpt:
As for the tumor response rate, the pooled ORR and DCR of all studies reached 57% (95% CI: 47%–67%) and 92% (95% CI: 89%–96%) respectively, and the pooled ORRs of the HER2-low expression group and the HER2-positive expression group were 46% (95% CI: 35%–56%) and 64% (95% CI: 54%–74%)....The present study suggests that DS-8201 is effective and safe in the treatment of ABC with low or positive HER2 expression...
DOI:
https://doi.org/10.3389/fphar.2023.1183514
Source:
Title:
Novel Anti-HER2 Antibody-Drug Conjugates Versus T-DM1 for HER2-Positive Metastatic Breast Cancer After Tyrosine Kinase Inhibitors Treatment
Published date:
05/22/2023
Excerpt:
In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1….In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.
DOI:
10.1093/oncolo/oyad127
Source:
Title:
236P - Trastuzumab deruxtecan in italian real-world experience: updated analysis from DE-REAL study
Published date:
05/07/2023
Excerpt:
Clinical and pathological information about pts with HER2+ mBC who received TDXd were collected from 11 italian hospitals….Among 123 pts with measurable disease, the ORR was 68% and the disease control rate was 91% (9 CRs, 74 PRs, and 30 SD).
Source:
Title:
237P - Real-world safety and efficacy of Trastuzumab-Deruxtecan (T-DXd) in HER2-positive advanced breast cancer (ABC) elderly patients (pts): the TREX-Old retrospective registry
Published date:
05/07/2023
Excerpt:
The aim of this retrospective analysis was to evaluate the safety and efficacy of T-DXd in ABC pts over 70 in a real-life setting….Finally, at a median follow-up of 9.5 months (1-29), median PFS was 12 months...
Source:
Title:
PD7-01 Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: A multicenter retrospective study (ROSET-BM study)
Published date:
11/22/2022
Excerpt:
ORR assessed by investigator was 55.7% (complete response [CR], 5.2%) in all pts, 51.7% (CR, 6.9%) in symptomatic BM pts (n=29), and 57.4% (CR, 4.4%) in asymptomatic BM pts (n=68). Among all pts, median PFS was 16.1 months (95%CI, 12.0–n/a)…The results of this retrospective chart review show that T-DXd has promising efficacy in HER2+ MBC pts with active BM and LMC.
Source:
Title:
Methods for Estimating Long-Term Outcomes for Trastuzumab Deruxtecan in HER2-Positive Unresectable or Metastatic Breast Cancer After Two or More Anti-HER2 Therapies
Published date:
11/07/2022
Excerpt:
Both extrapolation methods demonstrated longer mean/median OS with T-DXd versus eribulin, and capecitabine (44.7/32.9 months [applying an HR to the T-DM1 OS curve]; 47.7/29.9 months [using direct extrapolation]; vs 11.3/9.2, and 17.8/13.6 months, respectively)...Alternative methods produced consistent results, showing T-DXd is associated with substantial gains in OS and QALYs versus eribulin, and capecitabine.
DOI:
10.1007/s11523-022-00923-9
Trial ID:
Source:
Title:
Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis
Published date:
10/18/2022
Excerpt:
...trastuzumab deruxtecan (T-DXd; DS-8201) in patients with heavily pretreated HER2-positive metastatic breast cancer...Eight patients (47.1%) experienced a best overall intracranial response of partial response or complete response.
DOI:
10.1158/2159-8290.CD-22-0837
Trial ID:
Source:
Title:
Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases
Published date:
09/08/2022
Excerpt:
In a retrospective multi-institutional cohort study of 17 patients with predominantly HER2-positive BCBMs, the CNS objective response rate (ORR) was 73% (11/15) while extracranial response rate was 45% (5/11. In the subset of patients with untreated or progressive BCBM at baseline the CNS ORR was 70% (7/10)....T-DXd demonstrates evidence of CNS activity in HER2-positive and HER2-low PDX models of BCBM and preliminary evidence of clinical efficacy in a multi-institution case series of patients with BCBM.
DOI:
10.1158/1078-0432.CCR-22-1138
Source:
Title:
281MO - Quality of life and neurocognitive function in patients with active brain metastases of HER2-positive breast cancer treated with trastuzumab-deruxtecan: Secondary endpoint analysis of the prospective single-arm phase II TUXEDO-1 trial
Published date:
09/05/2022
Excerpt:
TUXEDO-1 is a prospective, open-label, single-arm phase II trial and enrolled adult HER2-positive BC pts with newly diagnosed BM...T-DXd was administered every three weeks at standard dose...TUXEDO-1 showed maintained QoL and neurocognitive function during T-DXd therapy in HER2-positive BC BM pts. Our data support first-line systemic therapy with T-DXd in pts with active BM.
Trial ID:
Source:
Title:
Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial
Published date:
08/08/2022
Excerpt:
Two patients (13.3%) had a complete intracranial response, nine (60%) had a partial intracranial response and three (20%) had stable disease as the best intracranial response, with a best overall intracranial response rate of 73.3% (95% confidential interval 48.1-89.1%), thus meeting the predefined primary outcome....trastuzumab deruxtecan showed a high intracranial response rate in patients with active brain metastases from HER2-positive breast cancer...
DOI:
10.1038/s41591-022-01935-8.
Trial ID:
Source:
Title:
Trastuzumab Deruxtecan in Patients with Central Nervous System Involvement from HER2-Positive Breast Cancer: The DEBBRAH Trial
Published date:
05/26/2022
Excerpt:
HER2-positive ABC patients...Patients received 5.4 mg/kg T-DXd intravenously...In cohort 1, 16-week PFS rate was 87.5% (95%CI, 47.3–99.7; P<.001). ORR-IC was 50.0% (95%CI, 6.7–93.2) in cohort 2 and 44.4% (95%CI, 13.7–78.8; P<.001) in cohort 3....
DOI:
https://doi.org/10.1093/neuonc/noac144
Trial ID:
Source:
Title:
165MO - Trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients (pts) with active brain metastases: Primary outcome analysis from the TUXEDO-1 trial
Published date:
05/03/2022
Excerpt:
TUXEDO-1 included adult pts with HER2-positive BC...In the intention-to-treat population, intracranial RR was 73.3% (11/15) (per protocol population: 78.6% [11/14]). At 11 months median follow-up, PFS was 14 months (95% CI 8.48-19.52); two pts died from disease progression. In the TUXEDO-1 study, T-DXd yielded high intracranial response rates. Data suggest that T-DXd achieves significant therapeutic effects in the central nervous system...
Trial ID:
Source:
Title:
5257 - Durable clinical and radiographic responses in a series of patients with HER2+ Breast Cancer (BC) Leptomeningeal Disease (LMD) treated with trastuzumab deruxtecan (T-DXd)
Published date:
03/09/2022
Excerpt:
Of the 6 patients included, median age was 42.5 years with 5 median lines of prior therapy. All 6 patients (100%) derived CB and 5 /6 (83.3%) had objective response on MRI. Patients were treated with a median 6.5 (5-23) cycles. Median duration of T-DXd therapy was 5.3 months (4.1-16.9) with 4 /6 patients receiving ongoing treatment. The median survival from initial diagnosis of LMD to death or last follow-up was 12.5 months. In this case series, 5/6 patients had radiographic responses without clinical progression, with median duration of treatment nearing 6 months and 4/6 patients continuing T-DXd at data cutoff. This series provides rationale for prospective evaluation of T-DXd in HER2+ LMD patients across tumor types.
Source:
Title:
Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer
Published date:
01/03/2022
Excerpt:
We retrospectively analyzed data for patients with HER2-positive metastatic breast cancer who received T-DXd at our institution from April 2020 to March 2021....The median progression-free survival (PFS) was 9.7 months (95% confidence interval [CI], 7.0-not reached [NR]), and the objective response rate (ORR) was 61.9%....T-DXd demonstrated favorable activity in clinical practice.
DOI:
10.1016/j.breast.2022.01.002
Source:
Title:
PD4-06 - Trastuzumab deruxtecan in patients with HER2[+] or HER2-low-expressing advanced breast cancer and central nervous system involvement: Preliminary results from the DEBBRAH phase 2 study
Published date:
10/09/2021
Excerpt:
T-DXd demonstrated preliminary efficacy with manageable toxicity in pretreated pts with HER2[+] ABC with stable and progressing BM after local treatment.
Trial ID:
Source:
Title:
279P - Trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer (MBC): Updated survival results from a phase II trial (DESTINY-Breast01)
Published date:
09/13/2021
Excerpt:
With greater maturity, the updated mOS was 28.4 months (95% CI, 24.6-37.2 months), with 91 (49.5%) OS events. Estimated OS rate was 75% (95% CI, 67%-80%) at 18 months and 58% (95% CI, 51%-65%) at 24 months….These updated results continue to demonstrate the survival benefit of T-DXd in heavily previously treated patients with HER2-positive MBC...
Trial ID:
Source:
Title:
New Therapeutic Strategies in Advanced Nonoperable or Metastatic HER2-positive Breast Cancer
Published date:
06/21/2021
Excerpt:
Trastuzumab deruxtecan (T-DXd, DS-8201a), an optimised antibody drug conjugate (ADC) is in clinical trials, showing promising outcomes in patients with advanced, nonoperable or metastatic HER2-positive breast cancer who had already undergone intensive prior treatment.
DOI:
10.1055/a-1471-4063
Source:
Title:
Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: A subgroup analysis of the DESTINY-Breast01 trial.
Published date:
05/19/2021
Excerpt:
...In these pts, the objective response rate (ORR), median progression-free survival (mPFS), and median duration of response (mDoR) per independent central review with T-DXd 5.4 mg/kg were 58.3% (95% CI, 36.6%-77.9%), 18.1 mo (95% CI, 6.7-18.1 mo), and 16.9 mo (95% CI, 5.7-16.9 mo), respectively...T-DXd showed strong clinical activity in both the overall population of pts with HER2+ mBC and the subgroup of pts with BMs.
DOI:
10.1200/JCO.2021.39.15_suppl.526
Trial ID:
Source:
Title:
A Review of Fam-Trastuzumab Deruxtecan-nxki in HER2-Positive Breast Cancer
Published date:
02/25/2021
Excerpt:
Fam-trastuzumab deruxtecan-nxki is an effective treatment for HER2-positive breast cancer in the metastatic setting...
DOI:
10.1177/1060028021998320
Source:
Title:
Recommendation based on positive results from the DESTINY-Breast01 trial, which showed durable responses in patients with previously treated disease
Published date:
12/14/2020
Excerpt:
AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s trastuzumab deruxtecan has been recommended for conditional marketing authorisation in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer...the Committee for Medicinal Products for Human Use (CHMP)...based its positive opinion on results from the registrational DESTINY-Breast01 Phase II trial...trastuzumab deruxtecan demonstrated clinically meaningful and durable activity in patients who had received two or more prior anti-HER2 medicines.
Source:
Title:
Enhertu continues to demonstrate durable responses with new data from DESTINY-Breast01 in HER2-positive metastatic breast cancer
Published date:
12/10/2020
Excerpt:
Updated results from the positive DESTINY-Breast01 Phase II trial showed AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan) continued to demonstrate impressive efficacy and durable responses in patients with HER2-positive metastatic breast cancer...patients treated with Enhertu (5.4 mg/kg) achieved an objective response rate (ORR) of 61.4% and a median duration of response (DoR) of 20.8 months...
Source:
Title:
147P - Pharmacokinetics, safety, and efficacy of trastuzumab deruxtecan (T-DXd) with OATP1B/CYP3A inhibitors in patients with HER2-expressing advanced solid tumours
Published date:
05/23/2020
Excerpt:
Eligible patients (pts) had HER2-expressing (IHC ≥1+ and/or ISH+) unresectable/metastatic solid tumors...Breast cancer was the most common cancer (42.5%)...Confirmed ORR was 15/36 (41.7%) in pts with measurable tumors at baseline (n = 36).
Secondary therapy:
itraconazole + ritonavir
Trial ID:
Source:
Title:
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer
Published date:
02/13/2020
Excerpt:
...evaluated trastuzumab deruxtecan in adults with pathologically documented HER2-positive metastatic breast cancer...The median response duration was 14.8 months (95% CI, 13.8 to 16.9), and the median duration of progression-free survival was 16.4 months (95% CI, 12.7 to not reached).
DOI:
10.1056/NEJMoa1914510
Trial ID:
Source:
Title:
Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts
Published date:
05/16/2018
Excerpt:
...enrolls subjects (sbj) with HER2+ breast cancer (BC) post T-DM1, HER2+ gastric cancer (GC) post trastuzumab, HER2 low BC (IHC 1+ or 2+, ISH-), and other HER2-expressing solid tumors (IHC ≥1+)….Overall, RECIST-confirmed overall response rate (ORR) in the evaluable sbj was 81/160 (50.6%) with the highest ORR in HER2+ BC (64.2%)....DS-8201a shows antitumor activity in multiple tumor types with high ORR and durable responses in heavily pretreated sbj.
DOI:
10.1200/JCO.2018.36.15_suppl.2501
Trial ID:
Source:
Title:
[A Case of Bilateral HER2-Positive Invasive Ductal Carcinoma with Complete Response on One Side with Trastuzumab Deruxtecan]
Published date:
03/01/2023
Excerpt:
A 52-year-old female with stage Ⅳ, bilateral, HER2-positive, breast cancer as well as bilateral axillary lymph node(LN) metastasis and bilateral pulmonary metastasis was administered trastuzumab plus pertuzumab plus docetaxel as a standard chemotherapy....Pathological examination then confirmed that tumor cells were no longer present in the left breast and left axillary LN. In this case T-DXd was highly effective for the local treatment of intractable, HER2-positive, breast cancer.
Source:
Title:
Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan
Published date:
06/08/2022
Excerpt:
T-DXd achieved complete response despite heavy pretreatment. Three persistent, previously-irradiated lesions were biopsy-proven to represent treatment effect. Subsequent recurrence occurred upon treatment holiday; partial response was observed with rechallenge. This case suggests T-DXd is active in HER2+ breast cancer brain metastases and supports further prospective evaluation.
DOI:
10.2217/cns-2022-0010
Source:
Title:
33P - Visualizing trastuzumab-deruxtecan action in HER2+ breast cancer cells at nanoscale
Published date:
10/16/2023
Excerpt:
This study aimed to investigate the effects of Tz-Dxd on HER2+ breast cancer cell lines at the nanoscale level using high-resolution light and electron microscopy techniques, biochemistry and flow cytometry analysis…Tz-Dxd induced apoptosis in more than 50% of cells after 72 hours of treatment...These results suggest that Tz-Dxd has potent anti-tumor activity in vitro but might also induce cellular senescence, which would merit further investigation due to its uncertain role in cancer progression in the long run.
Source:
Title:
PD4-05 - Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases (BCBM)
Published date:
10/09/2021
Excerpt:
Treatment with 10 mg/kg T-DXd significantly prolonged survival in HER2+ BCBM PDX models DFBM-354 (67 vs 154 days, p=0.0018) and DFBM-355 (78 vs 156 days, p=0.0067) vs. vehicle control...Using BCBM PDX models we find that T-DXd prolongs survival in untreated HER2+ BCBM PDX models as well as in T-DM1 treated models.
