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Disease Analysis: Colorectal Cancer

  • ID: 5310264
  • Report
  • February 2021
  • Region: Global
  • 93 pages
  • Datamonitor Healthcare
Overview

Colorectal (or bowel) cancer refers to carcinomas arising in the epithelium of the large intestine at any point between the cecal valve and the anus. CRC typically develops through the proliferation of mucosal epithelial cells of the gastrointestinal (GI) wall, eventually forming a polyp or adenoma. As with many other cancers of the GI tract, the vast majority (>95%) are adenocarcinomas. Colorectal cancers may be broadly divided between the two major regions of the large intestine. Though some disagreement exists on precisely where the boundary between the colon and the rectum exists, it is generally agreed that a primary tumor < 15cm from the anal margin may be defined as rectum cancer and more distal tumors defined as colon cancer. Though colon cancers are more common than rectal cancers, when considered together, CRC stands as the third deadliest and fourth most diagnosed form of cancer worldwide.

Latest Key Takeaways

The publisher estimates that in 2018, there were 1.80 million incident cases of colorectal cancer (CRC) worldwide, and expects that number to increase to 1.95 million incident cases by 2027.

The majority of CRC diagnoses (60.9%) worldwide are colon cancer, ranging from 57.3% to 68.5% across regions.

CRC may be subdivided into two distinct categories based on the anatomical origin of the primary tumor - rectal cancer and colon cancer
Colon cancer is fairly evenly distributed between sexes, with males accounting for 52.5% of global colon cancer diagnoses in 2018, whereas rectum cancer is slightly more common among men, who made up 61.0% of diagnoses in 2018.

Although systemic therapy is administered in locoregional disease, typically as adjuvant treatment, such regimens consist of genericized chemotherapies. All branded agents are confined to metastatic, unresectable CRC (mCRC).

Conventional targeted treatments in CRC are angiogenesis inhibitors typically acting through the receptor tyrosine kinase (RTK) superfamily, including EGFR antagonists, such as Erbitux and Vectibix, and VEGFR antagonists, such as Cyramza, Zaltrap, and Avastin (the latter two inhibit VEGFR through its ligand, VEGF). Additionally, Stivarga is a polyspecific tyrosine kinase inhibitor (TKI), simultaneously targeting VEGFR, PDGFR, and EGFR in addition to non-tyrosine kinases c-KIT and RAF.

Treatment for mCRC is heavily dependent on gene expression, with many drugs being prescribed only for specific tumor profiles.

First- and particularly second-line metastatic mCRC have become very crowded treatment settings, with multiple combinations of chemotherapies and targeted agents competing for the same patient subsets.

Avastin, the first targeted agent launched in the indication, is the traditional standard of care and remains widely prescribed in both first- and second-line disease and across tumor profiles. However, the branded drug is approaching the end of its cycle and the recent launch of bevacizumab biosimilars will significantly erode its market share.

Despite biosimilar erosion of branded Avastin, bevacizumab’s potential incorporation into new, highly active combination therapies in first- and second-line mCRC stands to cement the drug’s status as a standard of care.

Tumors that are RAS/BRAF WT and EGFR+ are among the most common gene expression profiles, accounting for approximately 40% of CRCs. The EGFR antagonist Erbitux, among the first targeted agents launched in CRC alongside Avastin, remains the most commonly prescribed therapy for this subset of patients, despite the more recent addition of Vectibix in the same setting.

Erbitux has recently found a new use in a doublet with the RAF kinase inhibitor Braftovi for BRAF V600E mutants. The combination is highly active, but only 12-15% of CRCs are BRAF V600E+ and the regimen is currently confined to second-line use.

Anti PD-1 checkpoint inhibitors Opdivo and Keytruda have seen initial success in microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) mCRCs, although these comprise only 15% of patients.

The exploratory CheckMate 9X8 regimen of bevacizumab, Opdivo, and FOLFOX in front-line disease, currently in Phase II/III investigation, has the potential to both introduce a highly active combination to the CRC treatment landscape and also expand PD-1 inhibitor use to the wider patient population.

A suite of trial suspensions has shrunk the late-stage CRC pipeline to just five drugs (two of which are very recent additions). Included are the MEK inhibitor Mektovi, the first-in-class STAT3 agonist napabucasin, the novel folate Modufolin, the PARP inhibitor Lynparza, and the novel VEGFR inhibitor fruquintinib.
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OVERVIEW
  • Latest key takeaways
DISEASE BACKGROUND
  • Definition
  • Risk factors
  • Symptoms
  • Diagnosis
  • Prognosis
  • Patient segmentation
TREATMENT
  • Locoregional disease
  • Metastatic disease
  • Front-line therapy for unresectable metastatic disease
  • Second-line therapy for unresectable metastatic disease
  • Subsequent-line therapy for unresectable metastatic disease
  • Branded drugs summary
EPIDEMIOLOGY
  • Incidence methodology
MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS
  • Bio-Thera Follows EU Bevacizumab Biosimilar Filing With FDA Goal Date
  • Keytruda & Bavencio Win EU Nod For More Cancers
  • Keytruda And FDA’s Oncology Center of Excellence: The Regulatory Milestones Keep Coming
  • New China Approvals Include Amgen, Sanofi, Hengrui Drugs, Innovent Biosimilar
  • Braftovi BEACON Trial Lights Way To Approval In Colorectal Cancer
  • Mylan Reveals FDA Goal Date For Bevacizumab
PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS
  • Servier, Celsius Team To Seek Novel Colorectal Cancer Targets
  • Biomm Backs Bio-Thera’s Brazilian Bevacizumab
  • Solasia Gets Japanese Rights To Isofol’s Colorectal Cancer Therapy
  • Chi-Med, Lilly Update Partnership For Elunate In China
CLINICAL TRIAL LANDSCAPE
  • Sponsors by status
  • Sponsors by phase
  • Recent events
DRUG ASSESSMENT MODEL

MARKET DYNAMICS

FUTURE TRENDS
  • Bevacizumab to remain standard of care in first- and second-line disease
  • PD-1 inhibitor market share is stunted by competition and restrictive approvals, but a trial of Opdivo in the broader
  • population presents a rare opportunity for expansion
  • Biosimilar erosion to increase payer pressure
  • Substantial opportunity for next-generation chemotherapies
CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION
  • Napabucasin for Colorectal Cancer (February 9, 2021)
  • MRTX849 for Colorectal Cancer (October 25, 2020)
  • Keytruda for Colorectal Cancer (May 31, 2020)
  • CYAD-101 for Colorectal Cancer (May 30, 2020)
  • AMG 510 for Colorectal Cancer (May 29, 2020)
  • Enhertu for Colorectal Cancer (May 29, 2020)
  • Onvansertib for Colorectal Cancer (May 29, 2020)
  • RGX-202 for Colorectal Cancer (May 29, 2020)
  • Keytruda for Colorectal Cancer (April 2, 2020)
  • Pegilodecakin for Colorectal Cancer (January 30, 2020)
  • MRTX849 for Colorectal Cancer (October 28, 2019)
  • Braftovi for Colorectal Cancer (September 30, 2019)
  • Tukysa for Colorectal Cancer (September 29, 2019)
  • AMG 510 for Colorectal Cancer (September 27, 2019)
KEY UPCOMING EVENTS

KEY OPINION LEADER INSIGHTS

BIBLIOGRAPHY
  • Prescription information
APPENDIX

LIST OF FIGURES
Figure 1: US colorectal cancer death and incidence rates per 100,000
Figure 2: Trends in incident cases of colorectal cancer, 2018–27
Figure 3: Overview of pipeline drugs for colorectal cancer in the US
Figure 4: Pipeline drugs for colorectal cancer, by company
Figure 5: Pipeline drugs for colorectal cancer, by drug type
Figure 6: Pipeline drugs for colorectal cancer, by classification
Figure 7: Probability of success in the colorectal cancer pipeline
Figure 8: Clinical trials in colorectal cancer
Figure 9: Top 10 drugs for clinical trials in colorectal cancer
Figure 10: Top 10 companies for clinical trials in colorectal cancer
Figure 11: Trial locations in colorectal cancer
Figure 12: Colorectal cancer trials status
Figure 13: Colorectal cancer trials sponsors, by phase
Figure 14: The publisher’s drug assessment summary for colorectal cancer
Figure 15: Market dynamics for colorectal cancer
Figure 16: Future trends in colorectal cancer
Figure 17: Keytruda for Colorectal Cancer (May 31, 2020): Phase III - KEYNOTE-177
Figure 18: Enhertu for Colorectal Cancer (May 29, 2020): Phase II - DESTINY-CRC01
Figure 19: Onvansertib for Colorectal Cancer (May 29, 2020): Phase Ib/II - w/Avastin + FOLFIRI
Figure 20: Keytruda for Colorectal Cancer (April 2, 2020): Phase III - KEYNOTE-177
Figure 21: Tukysa for Colorectal Cancer (September 29, 2019): Phase II - MOUNTAINEER (w/Trastuzumab)
Figure 22: AMG 510 for Colorectal Cancer (September 27, 2019): Phase I/II - CodeBreaK 100
Figure 23: Key upcoming events in colorectal cancer

LIST OF TABLES
Table 1: TNM staging for colorectal cancer
Table 2: Recommended systemic therapy for locally advanced colorectal cancer
Table 3: Recommended front-line systemic therapy for unresectable colorectal cancer
Table 4: Recommended second-line systemic therapy for unresectable colorectal cancer
Table 5: Recommended ≥3rd-line systemic therapy for unresectable colorectal cancer
Table 6: Summary of branded drugs available for colorectal cancer
Table 7: Incident cases of colorectal cancer, 2018–27
Table 8: Proportion of colorectal cancer incident cases by cancer type, 2018
Table 9: Incident cases of colon cancer, by gender, 2018
Table 10: Incident cases of rectum cancer, by gender, 2018
Table 11: Marketed drugs for colorectal cancer
Table 12: Pipeline drugs for colorectal cancer in the US
Table 13: Historical global sales, by drug ($m), 2015–19
Table 14: Forecasted global sales, by drug ($m), 2021–25
Table 15: Napabucasin for Colorectal Cancer (February 9, 2021)
Table 16: MRTX849 for Colorectal Cancer (October 25, 2020)
Table 17: Keytruda for Colorectal Cancer (May 31, 2020)
Table 18: CYAD-101 for Colorectal Cancer (May 30, 2020)
Table 19: AMG 510 for Colorectal Cancer (May 29, 2020)
Table 20: Enhertu for Colorectal Cancer (May 29, 2020)
Table 21: Onvansertib for Colorectal Cancer (May 29, 2020)
Table 22: RGX-202 for Colorectal Cancer (May 29, 2020)
Table 23: Keytruda for Colorectal Cancer (April 2, 2020)
Table 24: Pegilodecakin for Colorectal Cancer (January 30, 2020)
Table 25: MRTX849 for Colorectal Cancer (October 28, 2019)
Table 26: Braftovi for Colorectal Cancer (September 30, 2019)
Table 27: Tukysa for Colorectal Cancer (September 29, 2019)
Table 28: AMG 510 for Colorectal Cancer (September 27, 2019)
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