DAIICHI SANKYO CO., LTD. This indication is approved under Accelerated Approval based on tumour 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.
Enhertu is a HER2-directed antibody-drug conjugate (ADC) and the FDA approval is based on the results of the registrational Phase II trial DESTINY-Breast01 of Enhertu (5.4mg/kg) monotherapy in patients with HER2-positive metastatic breast cancer. All patients received prior trastuzumab, trastuzumab emtansine and 66% had prior pertuzumab.
The Phase II trial results showed a confirmed objective response rate of 60.3% (n=111, 95% CI 52.9-67.4) including a 4.3% complete response rate (n=8) and a 56.0% partial response rate (n=103). A median duration of response of 14.8 months (95% CI 13.8-16.9) was demonstrated as of 1 August 2019.1 In addition, a median progression-free survival of 16.4 months (95% CI 12.7-not estimable), based upon a median duration of follow up of 11.1 months, was recently presented at the San Antonio Breast Cancer Symposium and published online in
The safety of Enhertu has been evaluated in a pooled analysis from both the Phase II trial DESTINY-Breast01 and the earlier Phase I trial among a total of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of Enhertu (5.4mg/kg).
The most common adverse reactions (greater than or equal to 20% of patients) were nausea, fatigue, vomiting, alopecia and constipation. Interstitial lung disease (ILD)/pneumonitis occurred in 9% of patients. Fatal outcomes due to ILD/pneumonitis occurred in six patients (2.6%) - two deaths previously reported in the Phase I trial and four deaths previously reported in the Phase II trial DESTINY-Breast01. Following an initial ILD management programme already in place, a further monitoring, management and educational campaign on ILD/pneumonitis was launched in 2019. Patients and physicians should be aware of ILD/pneumonitis and patients should be actively screened and monitored for potential signs and symptoms. If ILD/pneumonitis is identified, it should be managed with dose modification and steroid treatment according to management guidelines.2
A regulatory submission for the treatment of patients with HER2-positive metastatic breast cancer has also been made to
AstraZeneca and
Financial considerations
Following US approval, an amount of
Future sales of Enhertu in the US will be recognised by
About HER2-positive breast cancer
Approximately one in five breast cancers are HER2-positive.3,4 Despite recent improvements and approvals of new medicines, there remains significant unmet needs for patients with HER2-positive metastatic breast cancer.5,6 This disease remains incurable with patients eventually progressing after available treatments.5,6
About HER2
HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poor prognosis in patients with breast cancer.7 To be considered HER2-positive, tumour cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridisation (FISH). IHC test results are reported as: 0, IHC 1+, IHC 2+, or IHC 3+.3 A finding of IHC 3+ and/or FISH amplification is considered positive.3
About DESTINY-Breast01
DESTINY-Breast01 is a registrational Phase II, single-arm, open-label, global, multicentre, two-part trial evaluating the safety and efficacy of Enhertu in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine. The primary endpoint of the trial is objective response rate, as determined by independent central review. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival. Enrolment into DESTINY-Breast01 was completed in
About Enhertu
Enhertu (fam-trastuzumab deruxtecan-nxki in the US only; trastuzumab deruxtecan outside the US) is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced programme in AstraZeneca's ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ('payload') to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.
About Enhertu clinical development
A comprehensive development programme is underway globally with five registrational trials in HER2-expressing metastatic breast and gastric cancers including a trial in patients with metastatic breast cancer and low levels of HER2 expression. Phase II trials are underway for HER2-expressing advanced colorectal cancer, as well as metastatic non-squamous HER2-overexpressing or HER2-mutated non-small cell lung cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
About the collaboration between AstraZeneca and
In
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologic medicines in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca's main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in
By harnessing the power of four scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody-Drug Conjugates - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.
About AstraZeneca
Contact:
Tel: +44 203 749 5916
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