‘Ground-breaking’ breast cancer trial results fuel blockbuster drug hopes for AstraZeneca and Daiichi Sankyo’s Enhertu
The prospect of a new blockbuster cancer drug for AstraZeneca has grown after it announced stunning results from trials of Enhertu.
The Cambridge-based biopharmaceutical company is hopeful it could become the new standard of care for treating both HER2-positive metastatic breast cancer and HER2-mutant metastatic non-small cell lung cancer.
Enhertu is antibody drug conjugate (ADC) that AstraZeneca has developed with Japan-based pharma company Daiichi Sankyo, which is directed at HER2, a growth-promoting protein that can lead to more aggressive, faster-spreading cancers.
Results presented at the European Society for Medical Oncology (ESMO) Congress from the phase III DESTINY-Breast03 trial showed Enhertu reduced the risk of disease progression or death by 72 per cent compared to trastuzumab emtansine (T-DM1) – a drug sold as Kadcyla by Roche – in patients with HER2-positive metastatic breast cancer.
Dr Javier Cortés, head of the International Breast Cancer Center in Barcelona, said: “Patients with previously treated HER2-positive metastatic breast cancer will typically experience disease progression in less than a year with available HER2-directed treatments.
“The high and consistent benefit seen across efficacy endpoints and key subgroups of patients receiving Enhertu in DESTINY-Breast03 is remarkable and supports the potential of Enhertu to become the new standard of care for those who have previously been treated for HER2-positive metastatic breast cancer.”
Cambridge-based Susan Galbraith, AstraZeneca’s executive vice president, oncology R&D, said: “Today’s results are ground-breaking. Enhertu tripled progression-free survival as assessed by investigators, and provided a disease control rate exceeding 95 per cent compared to 77 per cent for T-DM1 in DESTINY-Breast03.”
The main toxicity concern over Enhertu relates to interstitial lung disease (ILD) and pneumonitis.
But Dr Galbraith said: “The safety profile was encouraging, with no grade four or five interstitial lung disease events in this trial. These unprecedented data represent a potential paradigm shift in the treatment of HER2-positive metastatic breast cancer, and illustrate the potential for Enhertu to transform more patient lives in earlier treatment settings.”
The company said it was too early to tell if Enhertu improved overall survival compared to Kadcyla, although noted there was a “strong trend” in its favour. Enhertu is already approved in the UK, US, EU and some other countries for these patients who have received two or more prior anti-HER2-based regimens.
Meanwhile, results from the phase II DESTINY-Lung01 trial also presented at ESMO showed Enhertu demonstrated robust and durable tumour response of 54.9 per cent in patients with HER2-mutant metastatic non-small cell lung cancer.
Dr Bob Li, from the Memorial Sloan Kettering Cancer Center, said: “Despite more than 20 years of research into HER2-mutations in non-small cell lung cancer, there are currently no approved HER2-targeted therapies for non-small cell lung cancer. Patients with HER2-mutant non-small cell lung cancer are associated with younger age, female sex, never-smoking history, and a poor prognosis with increased incidence of brain metastases, representing an unmet clinical need.
“The impressive results from DESTINY-Lung01 showed most patients experienced a reduction in tumour size with Enhertu treatment, suggesting this medicine has the potential to become the new standard of care for these patients.”
There were, however, two ILD or pneumonitis-related deaths among the 91 advanced patients on whom data was reported, with 24 cases of the conditions.
Dr Galbraith said the treatment has “transformative potential”.
The first Enhertu trial in Western patients with gastric cancer has also taken place, and showed clinically meaningful and durable tumour response in patients with HER2-positive metastatic and/or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma, previously treated with a trastuzumab-containing regimen.
Dr Galbraith said: “Patients often experience disease progression following initial therapies, and then face limited treatment options, so today’s news brings hope.”
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