Detailed positive results from the head-to-head DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan), the
At a prespecified interim analysis of DESTINY-Breast03, Enhertu demonstrated a 72% reduction in the risk of disease progression or death compared to T-DM1 (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p=7.8x10-22). After 15.5 and 13.9 months of follow-up in the Enhertu and T-DM1 arms respectively, the median PFS for patients treated with Enhertu was not reached (95% CI 18.5-NE) compared to 6.8 months for T-DM1 (95% CI 5.6-8.2) as assessed by blinded independent central review (BICR).
In the 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 T-DM1 (HR 0.26; 95% CI 0.20-0.35; p=6.5x10-24). A consistent PFS benefit was observed in key subgroups of patients treated with Enhertu, including those with a history of stable brain metastases.
There was a strong trend towards improved overall survival (OS) with Enhertu (HR 0.56; 95% CI 0.36-0.86; nominal p=0.007172), however this analysis is not yet mature and is not statistically significant. Nearly all patients treated with Enhertu were alive at one year (94.1%) compared to 85.9% of patients treated with T-DM1.
Confirmed objective response rate (ORR) more than doubled in the Enhertu arm versus the T-DM1 arm (79.7% vs. 34.2%). Forty-two (16.1%) complete responses (CR), and 166 (63.6%) partial responses (PR) were observed in patients treated with Enhertu compared to 23 (8.7%) CRs and 67 (25.5%) PRs in patients treated with T-DM1.
The safety profile of the most common adverse events with Enhertu in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified. The most common Grade 3 or higher treatment-emergent adverse events in the Enhertu arm were neutropenia (19.1%), thrombocytopenia (7.0%), leukopenia (6.6%) and nausea (6.6%).
There were 27 cases (10.5%) of treatment-related interstitial lung disease (ILD) or pneumonitis reported, as determined by an independent adjudication committee. The majority (9.7%) were low Grade (Grade 1 or Grade 2), with two Grade 3 (0.8%) events reported. No Grade 4 or Grade 5 ILD or pneumonitis events occurred.
DESTINY-Breast01 Updated Results
Updated results from the pivotal DESTINY-Breast01 Phase II trial were also presented at ESMO and showed that Enhertu (5.4 mg/kg) continued to demonstrate impressive efficacy and durable responses in patients with HER2-positive metastatic breast cancer following two or more prior HER2-based regimens.
With a median duration of follow-up of 26.5 months, a continued increase in response was seen in patients treated with Enhertu with an updated ORR of 62.0%, including one additional CR (7.1%). A median duration of response (DoR) of 18.2 months was also observed.
The median PFS was 19.4 months. In an exploratory analysis of OS with a median follow-up of 31.1 months, evaluated at a greater maturity (52%), the updated median OS was 29.1 months.
The overall safety and tolerability profile seen with Enhertu in DESTINY-Breast01 continues to be consistent with what has been previously observed. There has been one new case of treatment-related Grade 1 ILD or pneumonitis determined by an independent adjudication committee as of data cut-off of
Enhertu is approved 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 in the metastatic setting in the US,
Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.
Several presentations featured during the
HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.1 More than two million patients with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 Approximately one in five cases of breast cancer are considered HER2-positive.2
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers.3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.4
Despite initial treatment with trastuzumab and a taxane, people with HER2-positive metastatic breast cancer will often experience disease progression.5 More effective options are needed to further delay progression and extend survival.5-7
DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Secondary efficacy endpoints include OS, objective response rate, duration of response, clinical benefit rate, PFS based on investigator assessment and safety.
DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in
DESTINY-Breast01
DESTINY-Breast01 is a registrational Phase II, single-arm, open-label, global, multi-centre, two-part trial evaluating the safety and efficacy of Enhertu in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with T-DM1.
The primary endpoint of the trial is ORR, as determined by ICR. Secondary objectives include DoR, disease control rate, clinical benefit rate, PFS and OS.
DESTINY-Breast01 enrolled 253 patients at multiple sites in
Enhertu
Enhertu is a HER2-directed ADC. Designed using
Enhertu (5.4mg/kg) is approved in
Enhertu (6.4mg/kg) is also approved in
Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the 'ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers,' based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.
In
Driven by a growing understanding of breast cancer biology,
PARP inhibitor, Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation.
Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer,
To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer,
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that
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