Disease Analysis: Head and Neck Cancer
Author: Tom Tyler
Publisher: Datamonitor Healthcare
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Overview
Head and neck cancers (HNCs) are defined as any cancer that begins in cells of the oral cavity, pharynx, nose, sinuses, or salivary glands. These cancers are grouped together due to historical similarities in etiology, disease presentation, and manifestation. The vast majority of these cases (>90%), collectively referred to as head and neck squamous cell carcinomas (HNSCCs), appear in squamous epithelial cells lining the mucous membranes of these regions.
Latest key takeaways
- Datamonitor Healthcare estimates that in 2018, there were 880,700 incident cases of head and neck cancer (HNC) worldwide, and expects that number to increase to 967,000 incident cases by 2027.
- The majority of HNC diagnoses (75.2%) worldwide are in men, ranging from 64.9% to 76.3% across regions.
- Though a heterogenous group of diseases, the overwhelming majority (>90%) of HNCs are comprised of head and neck squamous cell carcinomas (HNSCCs). Nasopharyngeal cancer, the second most common subtype, is widespread in East Asia but comparatively rare in Western nations.
- Most HNC patients are treated with surgery, radiotherapy, and/or platinum-based chemotherapy.
- Erbitux, once among the dominant branded systemic therapies for HNC, is being eclipsed by newer checkpoint inhibitors. Erbitux is approved for use in combination with radiation therapy to treat patients with unresectable HNSCC and both first- and second-line recurrent/metastatic HNSCC as a single agent and alongside chemotherapy.
- HNSCC tumors are highly immunogenic and have elevated expression of immune checkpoint modulators. As such, there has been much interest in the development of immunotherapies to allow for targeted treatment programs.
- The first immunotherapies approved for recurrent/metastatic HNSCCs are anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) Keytruda (for first and second line) and Opdivo (second line only). They have quickly established themselves as the most successful marketed drugs in this treatment setting.
- Numerous setbacks involving pipeline therapies for advanced HNSCCs, such as Imfinzi, Gilotrif, Bavencio, retifanlimab, and enoblituzumab, have allowed Keytruda and Opdivo to consolidate their leading positions in this setting. More generally, these failures reflect the unusually challenging R&D sphere in HNC, where the average probability a drug candidate advances from Phase III is 23.8%, significantly lower than the average of 47% in oncology as a whole.
- Keytruda is favored by US physicians, and, unlike Opdivo, is available for first- as well as second-line intervention for recurrent/metastatic HNSCC. A reversal of earlier negative NICE guidance has also led to widespread use in the UK.
- The ongoing Phase III CheckMate 651 trial seeks to gain approval for Opdivo for first-line recurrent/metastatic HNSCC and challenge Keytruda in this setting.
- Keytruda is in Phase III trials in the potentially lucrative locally advanced HNSCC setting. KEYNOTE-412 is evaluating Keytruda combined with chemoradiation and as maintenance therapy for non-resectable HNSCC, a setting now rendered largely unchallenged since the suspension of Bavencio in the JAVELIN Head and Neck 100 trial. KEYNOTE-689 is evaluating Keytruda as a neoadjuvant therapy and in combination with standard-of-care adjuvant therapy for resectable HNSCC. Success in these areas would result in unrivaled availability across the HNSCC treatment landscape.
- The other PD-1/PD-L1 antibody in Phase III development for newly diagnosed, locally advanced HNSCC is Tecentriq. The IMvoke010 trial is evaluating Tecentriq as a single-agent adjuvant therapy for resectable, locally advanced HNSCC. This may offer an attractive alternative by using checkpoint inhibition as a monotherapy in locally advanced HNSCC, thereby avoiding the toxicity of platinum-based chemotherapy.
- Monalizumab, an experimental checkpoint inhibitor, binds to the novel immune checkpoint target NKG2A. Continued development and potential approvals of additional immune checkpoint therapies are set to ensure the dominance of immuno-oncology agents in HNC for the foreseeable future.
- Though not threatening the dominance of ICIs in the treatment algorithm, experimental treatments such as the cytotoxic small molecule xevinapant and the farnesyltransferase inhibitor tipifarnib may provide therapeutic options for patients in hard-to-treat niches.
- Following the success of the JUPITER-02 trial and the failure of Keytruda’s KEYNOTE-122 study, Shanghai Junshi’s PD-1 antibody toripalimab stands to become the first targeted agent launched in nasopharyngeal cancer, and indeed the company’s first approved drug in a Western market.
- With high rates of recurrence and no approved targeted therapies, locally advanced HNSCCs remain an area of high unmet need. The immunocytokine cocktail Multikine recently showed some benefit as a neoadjuvant therapy among low-risk localized tumors, but the agent’s irregular development history and its trial’s mixed efficacy profile may prove barriers to approval.
- Further afield, the KEYNOTE-689 and IMvoke010 trials are evaluating the PD-(L)1 antibodies Keytruda and Tecentriq, respectively, alongside postoperative chemotherapy for high-risk localized tumors. These regimens may be better placed to address the unmet need posed by locally advanced HNSCC.
CONTENTS
8 OVERVIEW
8 Latest key takeaways
10 DISEASE BACKGROUND
10 Definition
10 Patient segmentation
11 Risk factors
12 Symptoms
13 Diagnosis
14 TREATMENT
14 Referral patterns
14 Standard of care by disease progression
14 Preferred systemic therapy regimens for locally advanced disease
15 Preferred systemic therapy regimens for very advanced disease
16 Approved marketed drugs
18 EPIDEMIOLOGY
18 Incidence methodology
22 MARKETED DRUGS
22 Head and neck cancer
25 Nasopharyngeal cancer
27 PIPELINE DRUGS
27 Head and neck cancer
42 Nasopharyngeal cancer
46 KEY REGULATORY EVENTS
46 China Inc. Shines In Latest Batch Of Approvals
46 Look East For New Checkpoint Inhibitors
46 Additional Keytruda Indication Among Latest China Approvals
46 First Approval For Rakuten Medical
47 PROBABILITY OF SUCCESS
48 LICENSING AND ASSET ACQUISITION DEALS
48 GSK Spends Heavily On iTeos’ TIGIT To Build A New IO Cornerstone
48 LianBio Licenses Cancer Radioenhancer From Nanobiotix
48 Shepherd Signs Oncology Alliances With Mayo, NCATS
48 Merck KGaA Bags Exclusive Rights To Develop, Sell Debiopharm’s Xevinapant
49 Nektar Finances Trial Via Capital, Collaboration With SFJ
49 China Grand Alliance With eTheRNA Follows Equity Investment
49 Gilead Buys Pipeline-In-A-Product With $21bn Immunomedics Deal
51 CLINICAL TRIAL LANDSCAPE
52 Sponsors by status
53 Sponsors by phase
54 Recent events
56 DRUG ASSESSMENT MODEL
59 MARKET DYNAMICS
60 FUTURE TRENDS
60 Standard of care shifting to immunotherapies
60 Poor trial results jeopardize development of immune checkpoint inhibitor doublets
61 Keytruda’s dominant position bolstered by label expansions
61 Immunotherapies compete for approval in locoregional HNSCC
61 Other pipeline drug classes lag behind checkpoint inhibitors
63 CONSENSUS FORECASTS
65 RECENT EVENTS AND ANALYST OPINION
65 Multikine for Head and Neck Cancer (June 28, 2021)
66 Toripalimab for Nasopharyngeal Cancer (June 3, 2021)
68 Tislelizumab for Nasopharyngeal Cancer (May 21, 2021)
70 Ficlatuzumab for Head and Neck Cancer (May 19, 2021)
72 Feladilimab for Head and Neck Cancer (April 14, 2021)
73 Imfinzi for Head and Neck Cancer (February 5, 2021)
74 mRNA-4157 for Head and Neck Cancer (November 11, 2020)
76 Toripalimab for Nasopharyngeal Cancer (September 28, 2020)
78 Bavencio for Head and Neck Cancer (September 19, 2020)
79 SNS-301 for Head and Neck Cancer (September 18, 2020)
80 ALX148 for Head and Neck Cancer (May 29, 2020)
81 Imfinzi for Head and Neck Cancer (May 29, 2020)
83 NBTXR3 (Drug) for Head and Neck Cancer (May 29, 2020)
85 Tipifarnib (Oncology) for Head and Neck Cancer (May 29, 2020)
87 Bavencio for Head and Neck Cancer (March 13, 2020)
89 KEY UPCOMING EVENTS
90 KEY OPINION LEADER INSIGHTS
91 BIBLIOGRAPHY
92 APPENDIX
LIST OF FIGURES
11 Figure 1: TNM classifications for HNSCCs
20 Figure 2: Trends in incident cases of head and neck cancer, 2018–27
27 Figure 3: Overview of pipeline drugs for head and neck cancer in the US
28 Figure 4: Pipeline drugs for head and neck cancer, by company
28 Figure 5: Pipeline drugs for head and neck cancer, by drug type
29 Figure 6: Pipeline drugs for head and neck cancer, by classification
42 Figure 7: Overview of pipeline drugs for nasopharyngeal cancer in the US
42 Figure 8: Pipeline drugs for nasopharyngeal cancer, by company
43 Figure 9: Pipeline drugs for nasopharyngeal cancer, by drug type
43 Figure 10: Pipeline drugs for nasopharyngeal cancer, by classification
47 Figure 11: Probability of success in the head and neck cancer pipeline
51 Figure 12: Clinical trials in head and neck cancer
51 Figure 13: Top 10 drugs for clinical trials in head and neck cancer
52 Figure 14: Top 10 companies for clinical trials in head and neck cancer
52 Figure 15: Trial locations in head and neck cancer
53 Figure 16: Head and neck cancer trials status
54 Figure 17: Head and neck cancer trials sponsors, by phase
56 Figure 18: Datamonitor Healthcare’s drug assessment summary for head and neck cancer
59 Figure 19: Market dynamics in head and neck cancer
60 Figure 20: Future trends in head and neck cancer
66 Figure 21: Multikine for Head and Neck Cancer (June 28, 2021): Phase III – IT-MATTERS
68 Figure 22: Toripalimab for Nasopharyngeal Cancer (June 3, 2021): Phase III – JUPITER-02
70 Figure 23: Tislelizumab for Nasopharyngeal Cancer (May 21, 2021): Phase III – RATIONALE 309 (China)
72 Figure 24: Ficlatuzumab for Head and Neck Cancer (May 19, 2021): Phase II – w/wo Cetuximab (University of Arizona)
76 Figure 25: mRNA-4157 for Head and Neck Cancer (November 11, 2020): Phase I – KEYNOTE-603 (w/Pembrolizumab)
78 Figure 26: Toripalimab for Nasopharyngeal Cancer (September 28, 2020): Phase III – JUPITER-02
79 Figure 27: Bavencio for Head and Neck Cancer (September 19, 2020): Phase III – JAVELIN HEAD AND NECK 100
83 Figure 28: Imfinzi for Head and Neck Cancer (May 29, 2020): Phase II – CheckRad-CD8 (w/Tremelimumab)
85 Figure 29: NBTXR3 (Drug) for Head and Neck Cancer (May 29, 2020): Phase I – Study-1100 (w/Nivolumab or Pembrolizumab)
87 Figure 30: Tipifarnib (Oncology) for Head and Neck Cancer (May 29, 2020): Phase II – RUN-HN (HRAS Mutations)
89 Figure 31: Key upcoming events in head and neck cancer
LIST OF TABLES
11 Table 1: Head and neck cancer: ICD-10 diagnosis codes
15 Table 2: Recommended (Category 1) chemotherapy regimens for locally advanced disease, by origin of primary tumor
16 Table 3: Recommended (Category 1) systemic therapy regimens for very advanced disease, by origin of primary tumor
17 Table 4: Approved marketed drugs for head and neck cancer
19 Table 5: Incident cases of head and neck cancer, 2018–27
21 Table 6: Incident cases of head and neck cancer, by gender, 2018
23 Table 7: Marketed drugs for head and neck cancer
26 Table 8: Marketed drugs for nasopharyngeal cancer
30 Table 9: Pipeline drugs for head and neck cancer in the US
44 Table 10: Pipeline drugs for nasopharyngeal cancer in the US
63 Table 11: Historical global sales, by drug ($m), 2016–20
64 Table 12: Forecasted global sales, by drug ($m), 2021–25
65 Table 13: Multikine for Head and Neck Cancer (June 28, 2021)
67 Table 14: Toripalimab for Nasopharyngeal Cancer (June 3, 2021)
69 Table 15: Tislelizumab for Nasopharyngeal Cancer (May 21, 2021)
70 Table 16: Ficlatuzumab for Head and Neck Cancer (May 19, 2021)
73 Table 17: Feladilimab for Head and Neck Cancer (April 14, 2021)
74 Table 18: Imfinzi for Head and Neck Cancer (February 5, 2021)
75 Table 19: mRNA-4157 for Head and Neck Cancer (November 11, 2020)
77 Table 20: Toripalimab for Nasopharyngeal Cancer (September 28, 2020)
78 Table 21: Bavencio for Head and Neck Cancer (September 19, 2020)
80 Table 22: SNS-301 for Head and Neck Cancer (September 18, 2020)
81 Table 23: ALX148 for Head and Neck Cancer (May 29, 2020)
82 Table 24: Imfinzi for Head and Neck Cancer (May 29, 2020)
84 Table 25: NBTXR3 (Drug) for Head and Neck Cancer (May 29, 2020)
86 Table 26: Tipifarnib (Oncology) for Head and Neck Cancer (May 29, 2020)
88 Table 27: Bavencio for Head and Neck Cancer (March 13, 2020)
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