Disease Analysis: Colorectal Cancer
Author: Millie Gray
Publisher: Datamonitor Healthcare
- Description
- Contents
- Enquire
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
- Datamonitor Healthcare 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.
- CRC may be subdivided into two distinct categories based on the anatomical origin of the primary tumor – rectal cancer and colon cancer.
- The majority of CRC diagnoses (60.9%) worldwide are colon cancer, ranging from 57.3% to 68.5% across regions. 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 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.
- 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 CRC 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 lifecycle and the recent launches 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.
- Published on 19 November 2021 Disease Analysis: Colorectal cancer (CRC) 8 © Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed Anti-PD-1 checkpoint inhibitors Opdivo and Keytruda have seen initial success in microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) mCRC, although these comprise only 15% of patients. Newly approved PD-1 checkpoint inhibitor Jemperli will provide some competition for these two agents.
- 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 who are MSI normal/MMR proficient.
- A suite of trial suspensions has shrunk the late-stage CRC pipeline. Current Phase III drugs include the CDK antagonist Cosela, the KRAS inhibitor adagrasib, the novel folate Modufolin, the PARP inhibitor Lynparza, and the novel VEGFR inhibitor fruquintinib
CONTENTS
7 OVERVIEW
7 Latest key takeaways
9 DISEASE BACKGROUND
9 Definition
9 Risk factors
10 Symptoms
10 Diagnosis
10 Prognosis
11 Patient segmentation
14 TREATMENT
14 Locoregional disease
14 Metastatic disease
15 Front-line therapy for unresectable metastatic disease
16 Second-line therapy for unresectable metastatic disease
18 Subsequent-line therapy for unresectable metastatic disease
19 Branded drugs summary
23 EPIDEMIOLOGY
23 Incidence methodology
29 MARKETED DRUGS
35 PIPELINE DRUGS
52 KEY REGULATORY EVENTS
52 Apotex Breaks New Ground In Canada With Biosimilar Bevacizumab
52 SMC Tries To Catch Up After COVID-19 Backlog
52 Henlius Submits NDA For HLX04 To China’s NMPA
52 Amneal Takes A Step Forward On Biosimilars
53 Tislelizumab Chinese Supplemental BLA Accepted
53 NICE Recommends Keytruda As First-Line Treatment Option For Colorectal Cancer
53 Bio-Thera Follows EU Bevacizumab Biosimilar Filing With FDA Goal Date
53 Keytruda & Bavencio Win EU Nod For More Cancers
55 PROBABILITY OF SUCCESS
56 LICENSING AND ASSET ACQUISITION DEALS
56 Deal Watch: VERAXA And Indivumed To Jointly Discover Antibodies Against CRC Targets
56 Zai Lab Gets Greater China Rights To Mirati’s Adagrasib
56 MD Anderson Inks New Cancer Collaboration With Mirati
56 Servier, Celsius Team To Seek Novel Colorectal Cancer Targets
57 Biomm Backs Bio-Thera’s Brazilian Bevacizumab
58 CLINICAL TRIAL LANDSCAPE
59 Sponsors by status
60 Sponsors by phase
61 Recent events
65 DRUG ASSESSMENT MODEL
70 MARKET DYNAMICS
71 FUTURE TRENDS
71 Bevacizumab to remain standard of care in first- and second-line disease
71 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
72 Biosimilar erosion to increase payer pressure
72 Substantial opportunity for next-generation chemotherapies
74 CONSENSUS FORECASTS
77 RECENT EVENTS AND ANALYST OPINION
77 Lonsurf for Colorectal Cancer (October 22, 2021)
78 Tecentriq for Colorectal Cancer (September 18, 2021)
79 Multiple Drugs for Colorectal Cancer (June 4, 2021)
80 Stivarga for Colorectal Cancer (June 4, 2021)
82 Xpovio for Colorectal Cancer (June 4, 2021)
83 Napabucasin for Colorectal Cancer (February 9, 2021)
84 Adagrasib for Colorectal Cancer (October 25, 2020)
85 Keytruda for Colorectal Cancer (May 31, 2020)
87 CYAD-101 for Colorectal Cancer (May 30, 2020)
88 Enhertu for Colorectal Cancer (May 29, 2020)
90 Lumakras for Colorectal Cancer (May 29, 2020)
91 Onvansertib for Colorectal Cancer (May 29, 2020)
93 RGX-202 for Colorectal Cancer (May 29, 2020)
95 KEY UPCOMING EVENTS
96 KEY OPINION LEADER INSIGHTS
97 UNMET NEEDS
98 BIBLIOGRAPHY
99 APPENDIX
LIST OF FIGURES
11 Figure 1: US colorectal cancer death and incidence rates per 100,000, 1992–2017
25 Figure 2: Trends in incident cases of colorectal cancer, 2018–27
35 Figure 3: Overview of pipeline drugs for colorectal cancer in the US
35 Figure 4: Pipeline drugs for colorectal cancer, by company
36 Figure 5: Pipeline drugs for colorectal cancer, by drug type
36 Figure 6: Pipeline drugs for colorectal cancer, by classification
55 Figure 7: Probability of success in the colorectal cancer pipeline
58 Figure 8: Clinical trials in colorectal cancer
58 Figure 9: Top 10 drugs for clinical trials in colorectal cancer
59 Figure 10: Top 10 companies for clinical trials in colorectal cancer
59 Figure 11: Trial locations in colorectal cancer
60 Figure 12: Colorectal cancer trials status
61 Figure 13: Colorectal cancer trials sponsors, by phase
65 Figure 14: Datamonitor Healthcare’s drug assessment summary for colorectal cancer
70 Figure 15: Market dynamics for colorectal cancer
71 Figure 16: Future trends in colorectal cancer
78 Figure 17: Lonsurf for Colorectal Cancer (October 22, 2021): Phase III – SOLSTICE
79 Figure 18: Tecentriq for Colorectal Cancer (September 18, 2021): Phase II – AtezoTRIBE
82 Figure 19: Stivarga for Colorectal Cancer (June 4, 2021): Phase II – w/Opdivo (pMMR/MSS)
87 Figure 20: Keytruda for Colorectal Cancer (May 31, 2020): Phase III – KEYNOTE-177
90 Figure 21: Enhertu for Colorectal Cancer (May 29, 2020): Phase II – DESTINY-CRC01
93 Figure 22: Onvansertib for Colorectal Cancer (May 29, 2020): Phase Ib/II – w/Avastin + FOLFIRI
95 Figure 23: Key upcoming events in colorectal cancer
97 Figure 24: Unmet needs in colorectal cancer
LIST OF TABLES
12 Table 1: TNM staging for colorectal cancer
14 Table 2: Recommended systemic therapy for locally advanced colorectal cancer
16 Table 3: Recommended front-line systemic therapy for unresectable colorectal cancer
17 Table 4: Recommended second-line systemic therapy for unresectable colorectal cancer
19 Table 5: Recommended ≥3rd-line systemic therapy for unresectable colorectal cancer
21 Table 6: Summary of branded drugs available for colorectal cancer
24 Table 7: Incident cases of colorectal cancer, 2018–27
26 Table 8: Proportion of colorectal cancer incident cases by cancer type, 2018
27 Table 9: Incident cases of colon cancer, by gender, 2018
28 Table 10: Incident cases of rectum cancer, by gender, 2018
30 Table 11: Marketed drugs for colorectal cancer
37 Table 12: Pipeline drugs for colorectal cancer in the US
75 Table 13: Historical global sales, by drug ($m), 2016–20
76 Table 14: Forecasted global sales, by drug ($m), 2021–25
77 Table 15: Lonsurf for Colorectal Cancer (October 22, 2021)
78 Table 16: Tecentriq for Colorectal Cancer (September 18, 2021)
80 Table 17: Multiple Drugs for Colorectal Cancer (June 4, 2021)
81 Table 18: Stivarga for Colorectal Cancer (June 4, 2021)
83 Table 19: Xpovio for Colorectal Cancer (June 4, 2021)
84 Table 20: Napabucasin for Colorectal Cancer (February 9, 2021)
85 Table 21: Adagrasib for Colorectal Cancer (October 25, 2020)
86 Table 22: Keytruda for Colorectal Cancer (May 31, 2020)
88 Table 23: CYAD-101 for Colorectal Cancer (May 30, 2020)
89 Table 24: Enhertu for Colorectal Cancer (May 29, 2020)
91 Table 25: Lumakras for Colorectal Cancer (May 29, 2020)
92 Table 26: Onvansertib for Colorectal Cancer (May 29, 2020)
94 Table 27: RGX-202 for Colorectal Cancer (May 29, 2020)
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
Do you have a subscription to Datamonitor Healthcare, Biomedtracker or Meddevicetracker? You may already have access to these reports, contact your account manager or email pharma@informabi.com for further help or assistance.
Disease Analysis: Diabetic Nephropathy 
Sign up to the