Gastric Cancer Forecast and Market Analysis
|出版日期||內容資訊||英文 81 Pages
|胃癌的預測、市場分析 Gastric Cancer Forecast and Market Analysis|
|出版日期: 2020年08月05日||內容資訊: 英文 81 Pages|
Stomach or gastric cancer (GC) refers to any cancer arising in the lining of the stomach. The vast majority (95%) of these cancers are adenocarcinomas, and can be further grouped by anatomic origin. The clearest etiological distinction exists between adenocarcinomas of the gastric cardia (the anterior edge of the stomach surrounding the entry point of the esophagus), and those arising in the other anatomical subsites of the stomach - the fundus, body, pylorus, and the antrum. In most cases, gastric adenocarcinomas will begin in the muscularis mucosae and submucosa, then invading deeper lamina of the gastric wall.
Datamonitor Healthcare estimates that in 2018, there were 1.0 million incident cases of gastric cancer worldwide in adults aged 20 years and older, and forecasts that number to increase to 1.1 million cases by 2027.
The majority of gastric cancer diagnoses (66.1%) worldwide are in males, ranging from 54.3% to 68.3% across regions.
A major etiological factor of gastric cancer, especially in poorer countries, is Helicobacter pylori infection of the stomach wall. The declining prevalence of H. pylori may have an effect on the future number of case diagnoses.
Approximately 75% of all gastric cancer diagnoses are in Asia. Particularly high incidence rates in East Asia make Japan a very large market for gastric cancer medications.
Early-stage gastric cancer is often asymptomatic, meaning that most diagnoses are only made in advanced disease. An exception to this trend is Japan, where proactive screening often discovers tumors in a locoregional setting.
Due to the lack of curative treatments in advanced disease, the prognosis of gastric cancer is rather poor in most countries, with five-year survival rates standing at 20% worldwide. Even in Japan, where screening often catches early-stage tumors, relatively high rates of recurrence keep this rate at 71.5%.
HER2, PD-1, and receptor tyrosine kinases (RTKs) are the most common molecular targets for both branded and pipeline drugs. However, the treatment landscape remains dominated by non-targeted chemotherapies, with most targeted agents confined to one or two treatment settings, where they are typically administered alongside chemotherapy.
Despite a failed expansion to frontline therapy, the vascular endothelial growth factor receptor (VEGFR) antagonist Cyramza is arguably the most successful targeted therapy in gastric cancer, having become the standard of care in second-line disease.
Immune checkpoint inhibitors (ICIs) - specifically PD-1 antagonists Opdivo and Keytruda - are in development in multiple treatment settings but remain largely confined to heavily pretreated (≥3rd-line) patients in Japan and the US, respectively. Keytruda is also approved in second-line disease, but only for microsatellite instability-high (MSI-H) tumors; a small minority of the total population.
No targeted therapies exist for locoregional disease, although Opdivo and Keytruda are in ongoing Phase III trials for this setting.
Trastuzumab biosimilars are now available, leading to a sharp decline in the market share of Herceptin.
Set to succeed Herceptin, next-generation HER2 antibodies margetuximab and Enhertu (an antibody-drug conjugate) are now seeking approval in gastric cancer.
No targeted treatments are available for frontline HER2-negative gastric cancer (approximately 80% of cases), making it one of the largest areas of unmet need in gastric cancer. As a result, multiple drugs - including Opdivo, Yervoy, Keytruda, tislelizumab, bemarituzumab, and zolbetuximab - are now in late-stage development for this setting.
Though most pipeline drugs in late-stage development involve the classic molecular targets of PD-1/PD-L1 and RTKs, the poly (ADP-ribose) polymerase (PARP) inhibitor pamiparib is in development for second-line disease, and zolbetuximab explores the entirely novel target of claudin-18. Additionally, the pipeline ICI MGD013 is a dual-affinity re-targeting antibody (DART) that is bispecific to LAG3 as well as PD-1.
Underwhelming benefits seen in multiple Phase III trials of PD-1 inhibitor monotherapies (including KEYNOTE-062 and KEYNOTE-061 for Keytruda, ATTRACTION-2 for Opdivo, and JAVELIN Gastric 100 for Bavencio) raise the prospect that gastric cancer may be resistant to immunotherapy.
Given the inconclusive results of KEYNOTE-062, Keytruda's approval in first-line HER2-negative disease will likely hinge on KEYNOTE-859, which is evaluating Keytruda combined with chemotherapy and is slated for completion in 2023. As such, the Opdivo-Yervoy dual blockade combination of CheckMate 649 is positioned to reach the frontline gastric cancer market first, as results are expected in 2021.