AstraZeneca and Daiichi Sankyo announced Saturday that Enhertu (trastuzumab deruxtecan) demonstrated a 72% reduction in the risk of disease progression or death compared to Roche's Kadcyla (trastuzumab emtansine) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The results were presented at the European Society for Medical Oncology (ESMO) congress.
The companies said last month that at a prespecified interim analysis of the Phase III DESTINY-Breast03 trial, Enhertu showed superiority versus Kadcyla, meeting the study's primary endpoint of progression-free survival (PFS). Results disclosed at ESMO indicated that the median PFS for patients treated with Enhertu was not reached compared to 6.8 months for Kadcyla, as assessed by blinded independent central review.
AstraZeneca and Daiichi Sankyo added that for a key secondary endpoint of PFS assessed by investigators, patients treated with Enhertu experienced a three-fold improvement in PFS of 25.1 months versus 7.2 months for Kadcyla. Meanwhile, a "consistent" PFS benefit was observed in key subgroups of patients treated with Enhertu, including those with a history of stable brain metastases. Further, there was a "strong" trend towards improved overall survival (OS) with Enhertu, although this analysis is not yet mature and is not statistically significant (see table below for more results).
"The high and consistent benefit seen across efficacy endpoints and key subgroups of patients receiving Enhertu…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," remarked lead investigator Javier Cortés. Meanwhile, Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, said "in addition, the safety profile was encouraging with no Grade 4 or 5 interstitial lung disease events in this trial."
In the study, interstitial lung disease (ILD) occurred in 10.5% of patients receiving Enhertu, with 9.7% being Grade 1 or 2, compared to 1.9% for Kadcyla. The study authors noted that Enhertu had a "manageable toxicity" profile in the trial, with a "significant improvement" in ILD profile versus studies conducted in more heavily pretreated patients.
Enhertu is currently approved for the treatment of adults with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. The HER2-directed antibody-drug conjugate is also authorised for use in adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
AstraZeneca and Daiichi Sankyo also reported promising updated results at ESMO from cohort two of the Phase II DESTINY-Lung01 trial, which included 91 previously treated patients with HER2-mutant unresectable and/or metastatic non-squamous non-small-cell lung cancer. The companies previously announced data from 42 participants, with Enhertu associated with a confirmed ORR of 61.9% and disease control rate (DCR) of 90.5%.
The latest results showed that the ORR for Enhertu was 54.9%, including one complete response and 49 partial responses, while the DCR was 92.3%. Further, after a median follow-up of 13.1 months, the median duration of response for Enhertu was 9.3 months, with median PFS of 8.2 months and median OS of 17.8 months.
Lead investigator Bob Li remarked "the impressive results…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." However, two patients died in the study as a result of treatment-related ILD/pneumonitis, with Li noting that both had a history of lobectomy or partial lobectomy and had received immune checkpoint inhibitor therapy just before enrolment. Overall, there were 24 cases of ILD or pneumonitis in the trial, with 75% grade 1 or 2, while in addition to the deaths, four instances were classed as grade 3.
Join FirstWord editors Michael Flanagan, Virginia Li and Simon King on Wednesday 22 September (3pm GMT / 10am EST) for a discussion on five key takeaways from the ESMO congress. Register for free here.
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