Disease Analysis: Colorectal Cancer
Author: Dana Gheorghe
Publisher: Datamonitor Healthcare
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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.
Latest key takeaways
- Datamonitor Healthcare estimates that in 2021, there were 1.85 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 directed by the patient’s gene expression profile, 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.
- 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
8 OVERVIEW
8 Latest key takeaways
10 DISEASE BACKGROUND
10 Definition
10 Risk factors
11 Symptoms
11 Diagnosis
12 Prognosis
12 Patient segmentation
15 TREATMENT
15 Locoregional disease
15 Metastatic disease
16 Front-line therapy for unresectable metastatic disease
17 Second-line therapy for unresectable metastatic disease
19 Subsequent-line therapy for unresectable metastatic disease
20 Branded drugs summary
24 EPIDEMIOLOGY
24 Incidence methodology
30 MARKETED DRUGS
36 PIPELINE DRUGS
53 KEY REGULATORY EVENTS
53 Amneal Scores Second US Biosimilar Approval With Avastin Rival
53 CHMP Recommends Six Extensions Of Indications For Approved Medicines
53 Henlius Gets Fourth Chinese Biosimilar With Bevacizumab Nod
53 China’s Tot Biopharm Secures First Antibody Approval With Avastin Biosimilar
54 Bio-Thera’s Bevacizumab US Action Date Passes Without Approval
54 3D Med, Alphamab Get First SubQ Immuno-Oncology Approval, In China
54 Celltrion Confirms EU Bevacizumab Filing
55 Apotex Breaks New Ground In Canada With Biosimilar Bevacizumab
55 SMC Tries To Catch Up After COVID-19 Backlog
55 Henlius Submits NDA For HLX04 To China’s NMPA
55 Amneal Takes A Step Forward On Biosimilars
56 Tislelizumab Chinese Supplemental BLA Accepted
57 PROBABILITY OF SUCCESS
58 LICENSING AND ASSET ACQUISITION DEALS
58 EdiGene To Team With Peking University Cancer Hospital
58 CMR Surgical Moves Into Wales: Robotiaid Mewn Nghymru
58 ImmunoScape Inks Licensing Deal With Pure MHC
58 Tech Transfer Roundup: Endeavor Gets Worldwide Rights To ENV-201
59 Deal Watch: VERAXA And Indivumed To Jointly Discover Antibodies Against CRC Targets
59 Zai Lab Gets Greater China Rights To Mirati’s Adagrasib
60 CLINICAL TRIAL LANDSCAPE
61 Sponsors by status
62 Sponsors by phase
63 Recent events
66 DRUG ASSESSMENT MODEL
72 MARKET DYNAMICS
73 FUTURE TRENDS
73 Bevacizumab to remain standard of care in first- and second-line disease
73 PD-1/PD-L1 inhibitor market share is stunted by competition and restrictive approvals
74 Biosimilar erosion to increase payer pressure
74 Substantial opportunity for next-generation chemotherapies
75 CONSENSUS FORECASTS
78 RECENT EVENTS AND ANALYST OPINION
78 Vectibix for Colorectal Cancer (June 6, 2022)
79 Vectibix for Colorectal Cancer (June 5, 2022)
81 Mektovi for Colorectal Cancer (June 4, 2022)
82 Opdivo for Colorectal Cancer (May 26, 2022)
83 Lumakras for Colorectal Cancer (May 26, 2022)
84 Tukysa for Colorectal Cancer (May 23, 2022)
85 Cabometyx / Cometriq for Colorectal Cancer (January 18, 2022)
86 Lonsurf for Colorectal Cancer (October 22, 2021)
88 Tecentriq for Colorectal Cancer (September 18, 2021)
89 Multiple Drugs for Colorectal Cancer (June 4, 2021)
90 Stivarga for Colorectal Cancer (June 4, 2021)
92 Xpovio for Colorectal Cancer (June 4, 2021)
93 Napabucasin for Colorectal Cancer (February 9, 2021)
95 KEY UPCOMING EVENTS
96 KEY OPINION LEADER INSIGHTS
97 UNMET NEEDS
98 BIBLIOGRAPHY
99 APPENDIX
LIST OF FIGURES
12 Figure 1: US colorectal cancer death and incidence rates per 100,000, 1992–2019
26 Figure 2: Trends in incident cases of colorectal cancer, 2018–27
36 Figure 3: Overview of pipeline drugs for colorectal cancer in the US
36 Figure 4: Pipeline drugs for colorectal cancer, by company
37 Figure 5: Pipeline drugs for colorectal cancer, by drug type
37 Figure 6: Pipeline drugs for colorectal cancer, by classification
57 Figure 7: Probability of success in the colorectal cancer pipeline
60 Figure 8: Clinical trials in colorectal cancer
60 Figure 9: Top 10 drugs for clinical trials in colorectal cancer
61 Figure 10: Top 10 companies for clinical trials in colorectal cancer
61 Figure 11: Trial locations in colorectal cancer
62 Figure 12: Colorectal cancer trials status
63 Figure 13: Colorectal cancer trials sponsors, by phase
66 Figure 14: Datamonitor Healthcare’s drug assessment summary for colorectal cancer
72 Figure 15: Market dynamics in colorectal cancer
73 Figure 16: Future trends in colorectal cancer
79 Figure 17: Vectibix for Colorectal Cancer (June 6, 2022): Phase II – IMPROVE
82 Figure 18: Mektovi for Colorectal Cancer (June 4, 2022): Phase Ib – w/Pembrolizumab (KEYNOTE-651)
88 Figure 19: Lonsurf for Colorectal Cancer (October 22, 2021): Phase III – SOLSTICE
89 Figure 20: Tecentriq for Colorectal Cancer (September 18, 2021): Phase II – AtezoTRIBE
92 Figure 21: Stivarga for Colorectal Cancer (June 4, 2021): Phase II – w/Opdivo (pMMR/MSS)
95 Figure 22: Key upcoming events in colorectal cancer
97 Figure 23: Unmet needs in colorectal cancer
LIST OF TABLES
13 Table 1: TNM staging for colorectal cancer
15 Table 2: Recommended systemic therapy for locally advanced colorectal cancer
17 Table 3: Recommended front-line systemic therapy for unresectable colorectal cancer
18 Table 4: Recommended second-line systemic therapy for unresectable colorectal cancer
20 Table 5: Recommended ≥3rd-line systemic therapy for unresectable colorectal cancer
22 Table 6: Summary of branded drugs available for colorectal cancer
25 Table 7: Incident cases of colorectal cancer, 2018–27
27 Table 8: Proportion of colorectal cancer incident cases by cancer type, 2018
28 Table 9: Incident cases of colon cancer, by gender, 2018
29 Table 10: Incident cases of rectum cancer, by gender, 2018
31 Table 11: Marketed drugs for colorectal cancer
38 Table 12: Pipeline drugs for colorectal cancer in the US
76 Table 13: Historical global sales, by drug ($m), 2017–21
77 Table 14: Forecasted global sales, by drug ($m), 2022–26
78 Table 15: Vectibix for Colorectal Cancer (June 6, 2022)
80 Table 16: Vectibix for Colorectal Cancer (June 5, 2022)
81 Table 17: Mektovi for Colorectal Cancer (June 4, 2022)
82 Table 18: Opdivo for Colorectal Cancer (May 26, 2022)
83 Table 19: Lumakras for Colorectal Cancer (May 26, 2022)
84 Table 20: Tukysa for Colorectal Cancer (May 23, 2022)
85 Table 21: Cabometyx / Cometriq for Colorectal Cancer (January 18, 2022)
87 Table 22: Lonsurf for Colorectal Cancer (October 22, 2021)
88 Table 23: Tecentriq for Colorectal Cancer (September 18, 2021)
90 Table 24: Multiple Drugs for Colorectal Cancer (June 4, 2021)
91 Table 25: Stivarga for Colorectal Cancer (June 4, 2021)
93 Table 26: Xpovio for Colorectal Cancer (June 4, 2021)
94 Table 27: Napabucasin for Colorectal Cancer (February 9, 2021)
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