First Enhertu trial in Western patients with gastric cancer Efficacy and safety results consistent with registrational DESTINY-Gastric01 will support ongoing discussions with global health authorities
Detailed results from the positive Phase II DESTINY-Gastric02 trial showed that Enhertu (trastuzumab deruxtecan), the
Gastric cancer is associated with a poor prognosis, particularly in the advanced stages of the disease, with only 5% to 10% of metastatic patients surviving five years globally.1,2 Approximately one in five gastric cancers are HER2-positive.3,4
In the primary analysis of DESTINY-Gastric02, the first trial of Enhertu specifically in Western patients with HER2-positive metastatic gastric cancer or GEJ adenocarcinoma, Enhertu (6.4 mg/kg) demonstrated a confirmed overall response rate (ORR) of 38% as assessed by independent central review (ICR). Three (3.8%) complete responses (CR) and 27 (34.2%) partial responses (PR) were observed in patients treated with Enhertu.
These results were consistent with those from the registrational DESTINY-Gastric01 Phase II trial previously published in
After a median follow-up of 5.7 months, the median duration of response (DoR) of Enhertu was 8.1 months (95% CI 4.1-NE). The median progression-free survival (PFS) was 5.5 months (95% CI 4.2-7.3). An exploratory endpoint of confirmed disease control rate (DCR) of 81% (95% CI; 70.6-89.0) was seen.
Summary of Results
Efficacy Measure
Total Evaluable (n=79)i,ii
Confirmed ORR (%) (95% CI)ii,iii
38.0% (27.3-49.6)
Complete response (%)
3.8%
Partial response (%)
34.2%
Stable disease (%)
43.0%
DCR (95% CI)iv
81% (70.6-89.0)
Median DoR (months) (95% CI)
8.1 months (4.1-NE)
Median PFS (months) (95% CI)
5.5 months (4.2-7.3)
i Enhertu 6.4 mg/kg; median duration of follow-up was 5.7 months.
ii As assessed by independent central review
iii ORR is (CR + PR)
iv DCR is (CR + PR +SD)
The overall safety profile of Enhertu in DESTINY-Gastric02 was consistent with that seen in DESTINY-Gastric01. The most common Grade 3 or higher drug-related treatment-emergent adverse events seen in DESTINY-Gastric02 were anaemia (7.6%), neutropenia (7.6%), nausea (3.8%) and fatigue (3.8%).
There were six cases (7.6%) of treatment-related interstitial lung disease (ILD) or pneumonitis reported, as determined by an independent adjudication committee. The majority (83%) were low Grade (Grade 1 or Grade 2), with one Grade 5 (ILD or pneumonitis-related death).
Enhertu is approved in
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
Gastric cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fourth highest leading cause of cancer mortality, with a five-year survival rate of 5% to 10% for advanced or metastatic disease.1,5 There were approximately one million new cases of gastric cancer and 768,000 deaths reported worldwide in 2020.6
Incidence rates for gastric cancer are markedly higher in eastern
Approximately one in five gastric cancers are HER2-positive.3,4 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.4 HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification.4
Recommended first-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy.7 For patients with metastatic gastric cancer that progresses following initial treatment with a trastuzumab-based regimen, treatment options are limited, and in many regions of the world, there are no additional HER2-directed medicines available.1,8,11
DESTINY-Gastric02
DESTINY-Gastric02 is a global, open-label, single-arm, Phase II trial evaluating the safety and efficacy of Enhertu (6.4mg/kg) in patients with HER2-positive metastatic and/or unresectable gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen.
The primary endpoint of DESTINY-Gastric02 is objective response rate (ORR), confirmed by Independent Central Review (ICR). Secondary endpoints include progression-free survival (PFS) confirmed by ICR, investigator assessed PFS, investigator assessed ORR, overall survival (OS) and duration of response (DoR).
DESTINY-Gastric02 enrolled 79 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
The Company aims to understand the potential of Enhertu in the two most common GI cancers, colorectal and gastric cancers. Imfinzi (durvalumab) is being assessed as both monotherapy and in combinations including with tremelimumab across the two main types of liver cancer, hepatocellular carcinoma and biliary tract cancer, and in oesophageal and gastric cancers.
Lynparza (olaparib) is a first-in-class PARP inhibitor with a broad and advanced clinical trial programme across multiple GI tumour types including pancreatic and colorectal cancers. Lynparza is development and commercialised in collaboration with MSD (
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that
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References
1. Casamayor M, et al. Targeted literature review of the global burden of gastric cancer. E cancer medical science. 2018;12:883.
2. SEER Survival rates: Stomach 2004-2017. Available at: https://seer.cancer.gov/explorer/application.html?site=18&data_type=4&graph_type=6&compareBy=sex&chk_sex_1=1&chk_sex_3=3&chk_sex_2=2&race=1&age_range=1&stage
=106&advopt_precision=1&advopt_show_ci=on&advopt_display=2. Accessed:
3. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014;852748.
4. Abrahao-Machado LF, et al. HER2 testing in gastric cancer: An Update. World J Gastroenterol. 2016;22(19):4619-4625.
5. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249.
6. WHO.
7. Oditura M, et al. Treatment of gastric cancer. World J Gastroenterol. 2014 Feb 21;20(7):1635-49.
8. Thuss-Patience PC, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18(5):640-653.
9. SEER Cancer Stat Facts: Stomach Cancer 2011-2017. Available at: https://seer.cancer.gov/statfacts/html/stomach.html. Accessed:
10.
11. Satoh T, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations:
12.
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