Enhertu (trastuzumab deruxtecan) has been granted conditional approval in the U.K. for the treatment of adults with inoperable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens.
A conditional approval is given to therapies whose benefit of immediate availability outweighs the risk of having less comprehensive data. Still, regulators require additional data or testing before granting full approval.
The decision of the Medicines and Healthcare products Regulatory Agency (MHRA) in the U.K. follows a similar ruling in the European Union on January 25.
“Trastuzumab deruxtecan offers an important new option for patients with HER2 positive metastatic breast cancer in the U.K. who are in need of new treatment options after their cancer has progressed beyond both 1st and 2nd line therapy,” Haran Maheson, commercial director for oncology for Daiichi Sankyo U.K., said in a press release.
“We will now work closely in partnership with the MHRA to fulfil all regulatory requirements before stock can be available in the U.K.,” Maheson added.
Previously known as DS-8201, Enhertu is an antibody-drug conjugate made up of trastuzumab, an antibody against HER2, bound to the cancer-killing agent deruxtecan, a derivative of exatecan. HER2 is a protein found on the surface of some breast cancers and linked to aggressive disease.
The therapy works by delivering deruxtecan directly to HER2-positive cancer cells, improving specificity and reducing off-target effects when compared with conventional chemotherapy.
The conditional approvals were based on data from the first 184 patients with HER2-positive metastatic breast cancer treated with Enhertu (5.4 mg/kg) in the DESTINY-Breast01 Phase 2 clinical trial (NCT03248492).
Adults involved in this study had previously been treated with at least two prior HER2 therapy regimens, including the antibody-drug conjugate Kadcycla (ado-trastuzumab emtansine). Primary completion is expected in February 2022.
As of June 2020, 61.4% of patients responded to Enhertu after a median follow-up of 20.5 months (over 1.5 years). A total of 6.5% of participants achieved a complete response — meaning cancer elimination — and over half (54.9%) obtained partial responses, or significant tumor shrinkage. Responses lasted a median of 20.8 months.
A pooled safety analysis was based on 234 patients treated with at least one dose of Enhertu in DESTINY-Breast01 and in other studies, with a median duration of treatment of 9.8 months.
The therapy was generally well-tolerated, with 33 treatment discontinuations (17.9% of patients) due to treatment-emergent side effects (adverse events). The most common adverse events, affecting more than 45% of the patients, included nausea, fatigue, vomiting, and hair loss. Additionally, constipation, decreased appetite, anemia, low white blood cell count, diarrhea, low platelet count, cough, and headache also were reported.
A total of 15% of patients developed lung tissue scarring — called interstitial lung disease, or ILD — or inflammation known as pneumonitis; 3% of patients died.
“The DESTINY-Breast01 trial showed a duration of response not previously seen in patients after progression on 1st and 2nd line treatment,” said Arun Krishna, head of oncology, AstraZeneca U.K.
The National Institute of Health and Care Excellence in England and the Scottish Medicines Consortium are currently conducting an appraisal of Enhertu. A decision on whether the therapy will be accessible via the National Health Service (NHS) is expected later this year.
“Trastuzumab deruxtecan is an important new treatment option for patients at this stage of care and will shift clinical discussions towards a focus on targeted treatment,” Krishna said.
“This is the first new cancer medicine to be authorised by the MHRA in 2021 and our focus now is on securing access for NHS patients as quickly as possible,” Krishan concluded.