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Articles

Safety in Lactation: Other antineoplastic drugs

23 September 2020Antineoplastic agents, whether used as monotherapy or in combination with other antineoplastics, are contra-indicated in breastfeeding (unless indicated below) because of their effects on dividing…

In use product safety assessment report for trastuzumab

3 May 2019A UKMi Product Safety assessment on  trastuzumab products (including the biosimilars) which describes the in-use medication safety considerations resultant from the product’s presentation or other…

Trastuzumab

12 January 2016Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the…
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New Medicines

EnhertuMetastatic breast cancer, unresectable or metastatic, HER2-positive, at least two previous anti-HER2 regimens

Information

Enhertu
New molecular entity
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

Launched
Approved (Licensed)
Launched
March 2021
Mar 21Available in the UK. 100mg powder for conc for soln for inf in vial, 1=£1,455 [19].
Feb 21Approved in the UK [18].
Jan 21Has been available in the US since Jan 20 [17].
Jan 21Granted conditional approval in EU [16].
Dec 20Recommended for EU approval by CHMP - the full indication is "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." It should be prescribed by physicians experienced in the use of anticancer medicinal products [15].
Jul 20European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for trastuzumab deruxtecan for the treatment of adults with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens and granted accelerated assessment [13].
Mar 20EU filing based on DESTINY-Breast01 planned for H2 20 [12].
Feb 20Analysts predict this will be one of the top 10 most-anticipated new US drug launches of 2020 based on estimated global sales in 2024 [11].
Dec 19Filings based on data from DESTINY-Breast 02 expected in 2021 [10].
Dec 19Approved in US via accelerated approval process, based on tumour response rate; continued licensing may be conditional on confirmation of clinical benefit [9].
Oct 19Filed in US with priority review [7].
Sep 19Filings based on DESTINY-Breast 01 planned for H2 2019 [6].
Jun 19Filings planned for 2020+ [5].
Aug 17US FDA grants Breakthrough Therapy Designation to trastuzumab deruxtecan for treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1) [3].
Dec 16US FDA grants Fast Track designation to trastuzumab deruxtecan for treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including ado-trastuzumab emtansine [3].

Category

Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the topoisomerase I inhibitor by a tetrapeptide linker.
In 2014, there were approximately 46,500 new diagnoses of breast cancer in England. It is estimated that approximately 15-25% of women with breast cancer will have HER2-positive tumours [1].
Metastatic breast cancer, unresectable or metastatic, HER2-positive, at least two previous anti-HER2 regimens
Intravenous infusion

Further information

Yes
May 2021

Trial or other data

Dec 19Results from the PII, single arm DESTINY-Breast01 trial found that trastuzumab deruxtecan led to an objective response rate of 60.9%. A cure rate of 6% was seen, and disease control rate of 97% (including some patients who experienced some tumour shrinkage, but not sufficient to be considered responders). Patients had received an average of six prior treatments. Side effects were experienced by 99% of patients, which included nausea, vomiting and low white blood cell counts. 15% of patients stopped treatment due to adverse events. Interstitial lung disease was experienced by 25 patients, four of whom died from the disease [8].
May 19AstraZeneca and Daiichi Sankyo announce PII DESTINY-Breast01 trial meets primary endpoint of objective response rate. Submission of a NDA to US FDA is planned for the second half of this year [4].
Aug 18PIII DESTINY-Breast03 trial to compare the anti-tumour activity as well as the safety and efficacy of trastuzumab deruxtecan versus T-DM1 (trastuzumab emtansine) in HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane (DS8201A-U302; NCT03529110). Progression-free survival is the primary endpoint of the trial. 500 patients will be recruited in the US and Japan. Collection of primary outcome data should complete Feb 22 [2].

Evidence based evaluations

EnhertuGastric or gastroesophageal cancer - HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer that had progressed after two or more treatments including trastuzumab and chemotherapy.

Information

Enhertu
Licence extension / variation
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

None
Phase II Clinical Trials
Launched
Yes
Jan 21Approved by US FDA for the treatment of adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen. Approval was based on data from the PII DESTINT-Gastric01 study. [12]
Oct 20The sBLA is based on results from the PII DESTINY-Gastric01 trial [11].
Oct 20FDA accepts sBLA with priority review. A regulatory decision is expected Q1 21 [9].
Oct 20Approved and launched in Japan [7].
Sep 20Has been filed in Japan [6].
May 20Enhertu granted Breakthrough Therapy designation and orphan status in the US for treatment of gastric cancer, including gastro-esophageal junction cancer [7]

Category

Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the topoisomerase I inhibitor by a tetrapeptide linker.
Gastric cancer is the second most common cause of cancer-related death in the world. It is a difficult disease to cure, mainly because most patients present with advanced disease. Around 6,700 people are diagnosed with stomach cancer in the UK each year [2014-16 data]. Around 20% of gastric cancers are HER2 positive. The number of people in the UK diagnosed with stomach cancer has been falling over the last 10 years. [1-3].
Gastric or gastroesophageal cancer - HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer that had progressed after two or more treatments including trastuzumab and chemotherapy.
Intravenous infusion

Further information

Yes
To be confirmed

Trial or other data

Jan 21In the PII DESTINT-Gastric01 study, Enhertu-treated pts had 41% reduction in the risk of death vs. chemotherapy-treated pts. At a pre-specified interim analysis, pts treated with Enhertu demonstrated a median OS of 12.5 months vs. 8.4 months with chemotherapy, a confirmed ORR of 40.5% with Enhertu vs. 11.3% with chemotherapy. The complete response rate (CRR) was 7.9% with Enhertu and partial response rate (PRR) was a 32.5% (vs. 0% and 11.3% for pts treated with chemotherapy). [12]
Dec 20PII DESTINY-Gastric-1 trial is due to finish following up patients. It completed collection of primary outcome data in Nov 19 [10].
May 20Detailed results from PII Gastric-01 trial presented at the American Society of Clinical Oncology virtual event. Patients treated with trastuzumab deruxtecan had a 41% reduction in the risk of death vs patients treated with chemotherapy (HR 0.59; 95% CI 0.39-0.88; p=0.0097) at a pre-specified interim analysis. The median OS was 12.5 months vs 8.4 months with chemotherapy. The estimated OS rate at one year in the trastuzumab deruxtecan arm was 52.1% and 28.9% with the chemotherapy arm [8].
Apr 20DESTINY-Gastric-1 trial meets primary endpoint [5].
Jan 20The PII open label, multi-centre, DESTINY-Gastric-1 trial of trastuzumab deruxtecan met its primary endpoint of % of pts with best objective Response within 22 months. It assessed the safety and efficacy of trastuzumab deruxtecan in 189 pts from Japan and South Korea with HER2+ advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who had progressed on >2 prior treatements including 5-FU, platinum chemotherapy and trastuzumab. Pts were randomised 2:1 to receive trastuzumab deruxtecan (6.4mg/kg once every 3 weeks) or either paclitaxel or irinotecan at standard doses. Secondary endpoints include OS, progression-free survival, duration of response, disease control rate and time to treatment failure as well as pharmacokinetic and safety endpoints. The estimated primary completion date is Sept 2020. [3,4]

Evidence based evaluations

EnhertuUnresectable or metastatic, HER2-positive breast cancer - second-line

Information

Enhertu
Licence extension / variation
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the topoisomerase I inhibitor by a tetrapeptide linker.
In 2014, there were approximately 46,500 new diagnoses of breast cancer in England. It is estimated that approximately 15-25% of women with breast cancer will have HER2-positive tumours [1].
Unresectable or metastatic, HER2-positive breast cancer - second-line
Intravenous infusion

Further information

Yes
To be confirmed

Evidence based evaluations

EnhertuMetastatic HER2-low breast cancer

Information

Enhertu
Licence extension / variation
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the topoisomerase I inhibitor by a tetrapeptide linker.
In 2014, there were approximately 46,500 new diagnoses of breast cancer in England. It is estimated that approximately 15-25% of women with breast cancer will have HER2-positive tumours [1].
Metastatic HER2-low breast cancer
Intravenous infusion

Evidence based evaluations

EnhertuMetastatic HER2-low, HR-positive breast cancer in patients who have progressed on endocrine therapy

Information

Enhertu
Licence extension / variation
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the topoisomerase I inhibitor by a tetrapeptide linker.
In 2014, there were approximately 46,500 new diagnoses of breast cancer in England. It is estimated that approximately 15-25% of women with breast cancer will have HER2-positive tumours [1].
Metastatic HER2-low, HR-positive breast cancer in patients who have progressed on endocrine therapy
Intravenous infusion

Enhertu HER2-positive high-risk breast cancer - post-neoadjuvant

Information

Enhertu
Licence extension / variation
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Antibody-drug conjugate composed of an anti-HER2 antibody, trastuzumab, and a DNA topoisomerase I inhibitor, a DX 8951 derivative. The HER2 antibody is attached to the topoisomerase I inhibitor by a tetrapeptide linker.
In 2014, there were approximately 46,500 new diagnoses of breast cancer in England. It is estimated that approximately 15-25% of women with breast cancer will have HER2-positive tumours [1].
HER2-positive high-risk breast cancer - post-neoadjuvant
Intravenous infusion

Enhertu HER2-positive metastatic breast cancer - first-line, with or without pertuzumab

Information

Enhertu
Licence extension / variation
Daiichi Sankyo
Daiichi Sankyo

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide. More than two million cases of breast cancer are diagnosed each year, resulting in nearly 685,000 deaths globally. Approximately one in five cases of breast cancer are considered HER2 positive [3].
HER2-positive metastatic breast cancer - first-line, with or without pertuzumab
Intravenous infusion