Disease Analysis: Colorectal Cancer
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-line 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-line and second-line disease and across tumor profiles. However, the branded drug is approaching the end of its lifecycle, and with several bevacizumab biosimilars already launched, its market share will continue to decrease. Nevertheless, bevacizumab’s potential incorporation into new, highly active combination therapies in first-line 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 5–12% 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 early-stage and up to 5% of metastatic patients. PD-1 checkpoint inhibitor Jemperli will provide some competition for these two agents, but its uptake will be limited by the low incidence of MSI-H/dMMR tumors in the metastatic setting.
- The late-stage CRC pipeline is swelling, with drugs spanning multiple drug classes being assessed. Current Phase III drugs include the CDK antagonist Cosela, KRAS inhibitors adagrasib and Lumakras, the VEGFR inhibitors fruquintinib and XL092, dual LAG3/immune checkpoint inhibitors Opdualag and favezelimab, immune checkpoint inhibitor Tecentriq, and vaccine GRANITE-001.
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
37 PIPELINE DRUGS
54 KEY REGULATORY EVENTS
54 Celltrion’s Vegzelma Becomes Fourth US-Approved Bevacizumab
54 Amneal Makes First Biosimilar Launch With US Bevacizumab
54 Celltrion To Jostle For Space In Crowded EU Bevacizumab Market
55 Innovent And Etana Get Indonesian Bevacizumab Nod
55 Viatris And Biocon Launch Bevacizumab Biosimilar In Canada
55 Amneal Scores Second US Biosimilar Approval With Avastin Rival
56 CHMP Recommends Six Extensions Of Indications For Approved Medicines
56 Henlius Gets Fourth Chinese Biosimilar With Bevacizumab Nod
56 China’s Tot Biopharm Secures First Antibody Approval With Avastin Biosimilar
57 Bio-Thera’s Bevacizumab US Action Date Passes Without Approval
57 3D Med, Alphamab Get First SubQ Immuno-Oncology Approval, In China
57 Celltrion Confirms EU Bevacizumab Filing
59 PROBABILITY OF SUCCESS
60 LICENSING AND ASSET ACQUISITION DEALS
60 Roche Goes Big On KRAS-Mutated Cancers In Hookipa Pact
60 Sareum’s Lead Asset Hangs In Balance As GSK Withdraws From Oncology Pact
60 Cancer Research UK, Sosei Team Up On Immunotherapy Trial
60 Erasca Five-Year Collaboration With MD Anderson Focused On MAPKlamp Combo
61 EdiGene To Team With Peking University Cancer Hospital
61 ImmunoScape Inks Licensing Deal With Pure MHC
61 Tech Transfer Roundup: Endeavor Gets Worldwide Rights To ENV-201
62 CLINICAL TRIAL LANDSCAPE
63 Sponsors by status
64 Sponsors by phase
65 Recent events
70 DRUG ASSESSMENT MODEL
77 MARKET DYNAMICS
78 FUTURE TRENDS
78 Bevacizumab to remain standard of care in first-line disease
78 PD-1/PD-L1 inhibitor market share is stunted by competition and restrictive approvals
79 Dual LAG3/immune checkpoint inhibition holds promise for improved efficacy
79 Biosimilar erosion to increase payer pressure
81 CONSENSUS FORECASTS
84 RECENT EVENTS AND ANALYST OPINION
84 Lonsurf for Colorectal Cancer (September 12, 2022)
85 Lumakras for Colorectal Cancer (September 12, 2022)
86 Adagrasib for Colorectal Cancer (September 7, 2022)
87 Fruquintinib for Colorectal Cancer (September 7, 2022)
88 Fruquintinib for Colorectal Cancer (August 7, 2022)
89 Modufolin for Colorectal Cancer (August 3, 2022)
90 Vectibix for Colorectal Cancer (June 6, 2022)
92 Vectibix for Colorectal Cancer (June 5, 2022)
94 Mektovi for Colorectal Cancer (June 4, 2022)
95 Opdivo for Colorectal Cancer (May 26, 2022)
96 Lumakras for Colorectal Cancer (May 26, 2022)
97 Tukysa for Colorectal Cancer (May 23, 2022)
98 Cabometyx / Cometriq for Colorectal Cancer (January 18, 2022)
99 Lonsurf for Colorectal Cancer (October 22, 2021)
101 Tecentriq for Colorectal Cancer (September 18, 2021)
102 Multiple Drugs for Colorectal Cancer (June 4, 2021)
103 Stivarga for Colorectal Cancer (June 4, 2021)
105 Xpovio for Colorectal Cancer (June 4, 2021)
107 KEY UPCOMING EVENTS
108 KEY OPINION LEADER INSIGHTS
109 UNMET NEEDS
110 BIBLIOGRAPHY
111 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
37 Figure 3: Overview of pipeline drugs for colorectal cancer in the US
37 Figure 4: Pipeline drugs for colorectal cancer, by company
38 Figure 5: Pipeline drugs for colorectal cancer, by drug type
38 Figure 6: Pipeline drugs for colorectal cancer, by classification
59 Figure 7: Probability of success in the colorectal cancer pipeline
62 Figure 8: Clinical trials in colorectal cancer
62 Figure 9: Top 10 drugs for clinical trials in colorectal cancer
63 Figure 10: Top 10 companies for clinical trials in colorectal cancer
63 Figure 11: Trial locations in colorectal cancer
64 Figure 12: Colorectal cancer trials status
65 Figure 13: Colorectal cancer trials sponsors, by phase
70 Figure 14: Datamonitor Healthcare’s drug assessment summary for colorectal cancer
77 Figure 15: Market dynamics in colorectal cancer
78 Figure 16: Future trends in colorectal cancer
90 Figure 17: Modufolin for Colorectal Cancer (August 3, 2022): Phase III – AGENT
92 Figure 18: Vectibix for Colorectal Cancer (June 6, 2022): Phase II – IMPROVE
95 Figure 19: Mektovi for Colorectal Cancer (June 4, 2022): Phase Ib – w/Pembrolizumab (KEYNOTE-651)
101 Figure 20: Lonsurf for Colorectal Cancer (October 22, 2021): Phase III – SOLSTICE
102 Figure 21: Tecentriq for Colorectal Cancer (September 18, 2021): Phase II – AtezoTRIBE
105 Figure 22: Stivarga for Colorectal Cancer (June 4, 2021): Phase II – w/Opdivo (pMMR/MSS)
107 Figure 23: Key upcoming events in colorectal cancer
109 Figure 24: 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
40 Table 12: Pipeline drugs for colorectal cancer in the US
82 Table 13: Historical global sales, by drug ($m), 2017–21
83 Table 14: Forecasted global sales, by drug ($m), 2022–26
84 Table 15: Lonsurf for Colorectal Cancer (September 12, 2022)
85 Table 16: Lumakras for Colorectal Cancer (September 12, 2022)
86 Table 17: Adagrasib for Colorectal Cancer (September 7, 2022)
87 Table 18: Fruquintinib for Colorectal Cancer (September 7, 2022)
88 Table 19: Fruquintinib for Colorectal Cancer (August 7, 2022)
89 Table 20: Modufolin for Colorectal Cancer (August 3, 2022)
91 Table 21: Vectibix for Colorectal Cancer (June 6, 2022)
93 Table 22: Vectibix for Colorectal Cancer (June 5, 2022)
94 Table 23: Mektovi for Colorectal Cancer (June 4, 2022)
95 Table 24: Opdivo for Colorectal Cancer (May 26, 2022)
96 Table 25: Lumakras for Colorectal Cancer (May 26, 2022)
97 Table 26: Tukysa for Colorectal Cancer (May 23, 2022)
98 Table 27: Cabometyx / Cometriq for Colorectal Cancer (January 18, 2022)
100 Table 28: Lonsurf for Colorectal Cancer (October 22, 2021)
101 Table 29: Tecentriq for Colorectal Cancer (September 18, 2021)
103 Table 30: Multiple Drugs for Colorectal Cancer (June 4, 2021)
104 Table 31: Stivarga for Colorectal Cancer (June 4, 2021)
106 Table 32: Xpovio for Colorectal Cancer (June 4, 2021)
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