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Disease Analysis: Gastric Cancer

  • ID: 5141806
  • Report
  • June 2021
  • Region: Global
  • 88 pages
  • Pharma Intelligence
Disease Overview

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.

Latest Key Takeaways
  • The publisher 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 incident 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. With H. pylori infections falling worldwide, the bacterium’s decreasing prevalence 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 front-line therapy, the vascular endothelial growth factor receptor (VEGFR) antagonist Cyramza has until recently been the most successful targeted therapy in gastric cancer, having become the standard of care in second-line disease.
  • Immune checkpoint inhibitors (ICIs) - specifically the PD-1 antagonists Opdivo and Keytruda - are in development in multiple treatment settings and have recently been made available for first-line disease following the success of KEYNOTE-811 and CheckMate 649.
  • 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 Margenza and Enhertu (an antibody-drug conjugate) are now expanding into gastric cancer, the latter of which has recently launched in Japan and the US.
  • Though most pipeline drugs in late-stage development involve the classic molecular targets of PD-1/PD-L1 and RTKs, zolbetuximab is exploring the entirely novel target of claudin-18. Additionally, the pipeline ICI tebotelimab is a dual-affinity re-targeting antibody (DART) that is bispecific to LAG3 as well as PD-1.
  • Until recently, no targeted agents were available for front-line HER2-negative gastric cancer (approximately 80% of cases), making it one of the largest areas of unmet need in the disease space. As a result, multiple drugs - including Opdivo, Yervoy, Keytruda, tislelizumab, bemarituzumab, and zolbetuximab - are now in late-stage development for this setting.
  • The Opdivo-chemotherapy combination arm of CheckMate 649 became the first and thus far the only targeted therapy to show a benefit in HER2-negative first-line disease, where it is now approved in the US. CheckMate 649 also features a dual blockade arm of Yervoy and Opdivo. This combination has not produced any results yet but is known from some other solid tumor indications to be highly active and may become a standard of care if found to be similarly effective in gastric cancer.
  • Underwhelming benefits seen in multiple Phase III trials of PD-1 inhibitor monotherapies (including in KEYNOTE-062 and KEYNOTE-061 for Keytruda and JAVELIN Gastric 100 for Bavencio) have stymied the launch of other single-agent checkpoint inhibitors in earlier lines of therapy, meaning that CheckMate 649 will be largely unchallenged for some time.
  • 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. KEYNOTE-062 also served as a confirmatory trial for Keytruda’s accelerated approval in third-line disease. This resulted in the FDA Oncologic Drugs Advisory Committee (ODAC) rescinding this approval (albeit in a staggered manner, so as to allow for sequencing of patients who were treated prior to the approval of Opdivo and thus were not able to receive a checkpoint inhibitor in the first line).
  • By contrast, KEYNOTE-811 yielded some better news for Keytruda in front-line gastric cancer, where a combination of the PD-1 antibody with trastuzumab showed promising results in first-line HER2-positive disease and was subsequently approved by the FDA. Though this is a smaller market than the HER2-negative population treated with Opdivo, it nonetheless presents an opportunity to improve the first-line standard of care for gastric tumors overexpressing HER2, which has remained entirely unchanged for over a decade since the initial approval of trastuzumab.
  • Two registration-enabling trials, DESTINY-Gastric04 and MOUNTAINEER-02 for Enhertu and Tukysa, respectively, are now underway following the success of Enhertu in heavily pretreated disease. Similar to the DESTINY-Gastric01 trial that produced Enhertu’s first approval in gastric cancer, these regimens are intended for HER2-positive tumors previously treated with trastuzumab, meaning patients may be able to receive two consecutive rounds of anti-HER2 interventions.
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OVERVIEW
  • Latest key takeaways
DISEASE BACKGROUND
  • Definition
  • Risk factors
  • Symptoms
  • Patient segmentation
  • Diagnosis
  • Prognosis
TREATMENT
  • Treatment techniques
  • Preferred systemic therapies for resectable locoregional disease
  • Preferred systemic therapies for advanced, unresectable or recurrent disease
  • Approved branded drugs
EPIDEMIOLOGY
  • Incidence methodology
MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS
  • Keytruda Shores Up Gastric Cancer Label
  • Keytruda’s Third-Line Gastric Cancer Indication Should Go, US FDA Panel Says
  • Opdivo First-Line Gastric Cancer Claim Used RTOR
  • Opdivo Seeks New Gastric Cancer Uses
  • FDA Approval Opens Up Gastric Cancer To Daiichi Sankyo/AZ’s Enhertu
  • AZ Looks To Convert Recent BTDs To Approvals For Enhertu, Tagrisso
'Sakigake' Treatment Gives Enhertu Rapid Japan OK For Gastric Cancer
  • Henlius’ Trastuzumab Approved In China
  • Enhertu Breaks Through In HER2-Positive Gastric Cancer
PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS
  • Genome & Co. Signs Extended IO Collaboration With Merck KGaA, Pfizer
  • Amgen Paying $1.9bn For Five Prime And Its Gastric Cancer Antibody
  • TRIGR, Elpiscience Partner On Cancer Immunotherapy In China
  • Prestige Lines Up Another Biosimilar Partner With Teva Subsidiary
  • Pfizer Bets $480m On CStone And Surging China Immuno-Oncology Market
  • Twice As Nice: Seattle Genetics, Merck & Co. Partner On Two Cancer Drugs
CLINICAL TRIAL LANDSCAPE
  • Sponsors by status
  • Sponsors by phase
  • Recent events
DRUG ASSESSMENT MODEL

MARKET DYNAMICS

FUTURE TRENDS
  • Brands scramble to launch in front-line HER2-negative advanced gastric cancer
  • New treatment options for HER2-positive patients on the horizon
  • Cyramza is likely to remain a standard of care in second-line disease
  • Declining prevalence of H. pylori may slow gastric cancer incidence growth
CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION
  • KN026 for Gastric Cancer (May 19, 2021)
  • Pamiparib for Gastric Cancer (May 19, 2021)
  • Keytruda for Gastric Cancer (May 5, 2021)
  • Keytruda for Gastric Cancer (April 29, 2021)
  • Keytruda for Gastric Cancer (April 23, 2021)
  • Bemarituzumab for Gastric Cancer (November 10, 2020)
  • Opdivo for Gastric Cancer (September 21, 2020)
  • Bavituximab for Gastric Cancer (September 18, 2020)
  • Opdivo for Gastric Cancer (August 11, 2020)
  • ALX148 for Gastric Cancer (May 29, 2020)
  • Enhertu for Gastric Cancer (May 29, 2020)
  • Enhertu for Gastric Cancer (January 27, 2020)
  • Motixafortide for Gastric Cancer (January 24, 2020)
  • Bavencio for Gastric Cancer (November 8, 2019)
KEY UPCOMING EVENTS

KEY OPINION LEADER INSIGHTS

UNMET NEEDS

BIBLIOGRAPHY

APPENDIX

LIST OF FIGURES
Figure 1: AJCC prognostic groups for gastric cancer (clinical staging)
Figure 2: Definitions of the diagnostic criteria for primary tumor (T), regional lymph nodes (N), and distant metastasis (M) in gastric cancer
Figure 3: Trends in incident cases of gastric cancer, 2018–27
Figure 4: Overview of pipeline drugs for gastric cancer in the US
Figure 5: Pipeline drugs for gastric cancer, by company
Figure 6: Pipeline drugs for gastric cancer, by drug type
Figure 7: Pipeline drugs for gastric cancer, by classification
Figure 8: Probability of success in the gastric cancer pipeline
Figure 9: Clinical trials in gastric cancer
Figure 10: Top 10 drugs for clinical trials in gastric cancer
Figure 11: Top 10 companies for clinical trials in gastric cancer
Figure 12: Trial locations in gastric cancer
Figure 13: Gastric cancer trials status
Figure 14: Gastric cancer trials sponsors, by phase
Figure 15: The publisher’s drug assessment summary for gastric cancer
Figure 16: Market dynamics in gastric cancer
Figure 17: Future trends in gastric cancer
Figure 18: Pamiparib for Gastric Cancer (May 19, 2021): Phase II - PARALLEL 303
Figure 19: Keytruda for Gastric Cancer (May 5, 2021): Phase III - KEYNOTE-811 (w/Trastuzumab)
Figure 20: Bemarituzumab for Gastric Cancer (November 10, 2020): Phase II - FIGHT (w/mFOLFOX6)
Figure 21: Opdivo for Gastric Cancer (September 21, 2020): Phase III - CheckMate-649 (w/Ipilimumab)
Figure 22: Bavituximab for Gastric Cancer (September 18, 2020): Phase II - w/Pembrolizumab
Figure 23: Opdivo for Gastric Cancer (August 11, 2020): Phase III - CheckMate-649
Figure 24: Enhertu for Gastric Cancer (May 29, 2020): Phase II - DESTINY-Gastric01 (Japan/Korea)
Figure 25: Enhertu for Gastric Cancer (January 27, 2020): Phase II - DESTINY-Gastric01 (Japan/Korea)
Figure 26: Motixafortide for Gastric Cancer (January 24, 2020): Phase Ib/II - G/GEJ UMBRELLA
Figure 27: Bavencio for Gastric Cancer (November 8, 2019): Phase III - JAVELIN Gastric 100
Figure 28: Key upcoming events in gastric cancer
Figure 29: Unmet needs in gastric cancer

LIST OF TABLES
Table 1: Recommended therapies for locally advanced, resectable gastric adenocarcinoma
Table 2: Recommended front-line systemic therapies for recurrent/metastatic and unresectable gastric cancer
Table 3: Recommended subsequent-line systemic therapies for recurrent/metastatic and unresectable gastric cancer
Table 4: Approved branded drugs for gastric cancer
Table 5: Incident cases of gastric cancer, 2018–27
Table 6: Incident cases of gastric cancer, by gender, 2018
Table 7: Marketed drugs for gastric cancer
Table 8: Pipeline drugs for gastric cancer in the US
Table 9: Historical global sales, by drug ($m), 2016–20
Table 10: Forecasted global sales, by drug ($m), 2021–25
Table 11: KN026 for Gastric Cancer (May 19, 2021)
Table 12: Pamiparib for Gastric Cancer (May 19, 2021)
Table 13: Keytruda for Gastric Cancer (May 5, 2021)
Table 14: Keytruda for Gastric Cancer (April 29, 2021)
Table 15: Keytruda for Gastric Cancer (April 23, 2021)
Table 16: Bemarituzumab for Gastric Cancer (November 10, 2020)
Table 17: Opdivo for Gastric Cancer (September 21, 2020)
Table 18: Bavituximab for Gastric Cancer (September 18, 2020)
Table 19: Opdivo for Gastric Cancer (August 11, 2020)
Table 20: ALX148 for Gastric Cancer (May 29, 2020)
Table 21: Enhertu for Gastric Cancer (May 29, 2020)
Table 22: Enhertu for Gastric Cancer (January 27, 2020)
Table 23: Motixafortide for Gastric Cancer (January 24, 2020)
Table 24: Bavencio for Gastric Cancer (November 8, 2019)
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