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). In this setting, Datamonitor Healthcare expects that ICIs will be used primarily for first-line patients, which should allow Keytruda, which is approved both as monotherapy and in combination with chemotherapy, to dominate over Opdivo.
- The tyrosine kinase inhibitor Lenvima is being evaluated in combination with Keytruda for first-line recurrent/metastatic HNSCC in the LEAP-010 Phase III trial. The combined approach of checkpoint blockade and anti-angiogenic intervention has proven efficacy in other solid tumor indications, particularly renal cell carcinoma, but it remains to be seen how such a regimen will fare in HNC.
- Numerous setbacks involving pipeline therapies for advanced HNSCCs such as Imfinzi, Gilotrif, Bavencio, retifanlimab, and enoblituzumab have allowed Keytruda to consolidate its leading position 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 47.2% in oncology as a whole.
- With high rates of recurrence and no approved targeted therapies, locally advanced HNSCCs remain an area of high unmet need as well as a potentially lucrative setting. 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.
- Keytruda is also in Phase III trials in the locally advanced HNSCC setting. KEYNOTE-412 is evaluating Keytruda combined with Published on 22 November 2021 Disease Analysis: Head and neck cancer 9 © Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed 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.
- Xevinapant, which promotes apoptosis, is being evaluated in combination with chemoradiotherapy for locally advanced, unresectable HNSCC.
- Four new regimens are being developed for second-line recurrent/metastatic HNSCC: buparlisib, a PI3 kinase inhibitor, combined with weekly paclitaxel; monalizumab, an antibody specific for the immune checkpoint NKG2A, combined with Erbitux; ISA101, a therapeutic anti-HPV16 vaccine, combined with Regeneron’s PD-1 inhibitor Libtayo in patients with HPV16-positive oropharyngeal cancer; and tipifarnib, an inhibitor of the posttranslational attachment of farnesyl groups to signaling proteins such as HRAS, in patients with HRAS-mutated HNSCC (HRAS is mutated in only 6% of HNSCCs at initial diagnosis).
- 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 one of the first targeted agents launched in nasopharyngeal cancer, and the company’s first approved drug in a Western market. Akeso’s penpulimab is another Chinese-developed PD-1 antibody currently under FDA regulatory review for nasopharyngeal cancer, with an approval decision due before the end of 2021.
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
43 Nasopharyngeal cancer
47 KEY REGULATORY EVENTS
47 Nasopharyngeal Cancer Is US Opening Act For Toripalimab, Penpulimab
47 China Inc. Shines In Latest Batch Of Approvals
47 Look East For New Checkpoint Inhibitors
47 Additional Keytruda Indication Among Latest China Approvals
49 PROBABILITY OF SUCCESS
50 LICENSING AND ASSET ACQUISITION DEALS
50 GSK Spends Heavily On iTeos’ TIGIT To Build A New IO Cornerstone
50 LianBio Licenses Cancer Radioenhancer From Nanobiotix
50 Shepherd Signs Oncology Alliances With Mayo, NCATS
50 Merck KGaA Bags Exclusive Rights To Develop, Sell Debiopharm’s Xevinapant
51 Nektar Finances Trial Via Capital, Collaboration With SFJ
51 China Grand Alliance With eTheRNA Follows Equity Investment
52 CLINICAL TRIAL LANDSCAPE
53 Sponsors by status
54 Sponsors by phase
55 Recent events
57 DRUG ASSESSMENT MODEL
61 MARKET DYNAMICS
62 FUTURE TRENDS
62 Standard of care shifting to immunotherapies, with Keytruda set to dominate
63 Other pipeline drug classes lag behind checkpoint inhibitors
63 New options are being developed for second-line recurrent/metastatic HNSCC
64 CONSENSUS FORECASTS
66 RECENT EVENTS AND ANALYST OPINION
66 HB-201 for Head and Neck Cancer (November 9, 2021)
68 Penpulimab for Nasopharyngeal Cancer (September 16, 2021)
70 Opdivo for Head and Neck Cancer (July 16, 2021)
71 Multikine for Head and Neck Cancer (June 28, 2021)
73 Toripalimab for Nasopharyngeal Cancer (June 3, 2021)
74 Tislelizumab for Nasopharyngeal Cancer (May 21, 2021)
76 Ficlatuzumab for Head and Neck Cancer (May 19, 2021)
78 Feladilimab for Head and Neck Cancer (April 14, 2021)
79 Imfinzi for Head and Neck Cancer (February 5, 2021)
80 mRNA-4157 for Head and Neck Cancer (November 11, 2020)
82 Toripalimab for Nasopharyngeal Cancer (September 28, 2020)
84 Bavencio for Head and Neck Cancer (September 19, 2020)
85 SNS-301 for Head and Neck Cancer (September 18, 2020)
86 ALX148 for Head and Neck Cancer (May 29, 2020)
87 Imfinzi for Head and Neck Cancer (May 29, 2020)
89 NBTXR3 (Drug) for Head and Neck Cancer (May 29, 2020)
91 Tipifarnib (Oncology) for Head and Neck Cancer (May 29, 2020)
94 KEY UPCOMING EVENTS
95 KEY OPINION LEADER INSIGHTS
96 BIBLIOGRAPHY
97 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
43 Figure 7: Overview of pipeline drugs for nasopharyngeal cancer in the US
43 Figure 8: Pipeline drugs for nasopharyngeal cancer, by company
44 Figure 9: Pipeline drugs for nasopharyngeal cancer, by drug type
44 Figure 10: Pipeline drugs for nasopharyngeal cancer, by classification
49 Figure 11: Probability of success in the head and neck cancer pipeline
52 Figure 12: Clinical trials in head and neck cancer
52 Figure 13: Top 10 drugs for clinical trials in head and neck cancer
53 Figure 14: Top 10 companies for clinical trials in head and neck cancer
53 Figure 15: Trial locations in head and neck cancer
54 Figure 16: Head and neck cancer trials status
55 Figure 17: Head and neck cancer trials sponsors, by phase
57 Figure 18: Datamonitor Healthcare’s drug assessment summary for head and neck cancer
61 Figure 19: Market dynamics in head and neck cancer
62 Figure 20: Future trends in head and neck cancer
68 Figure 21: HB-201 for Head and Neck Cancer (November 9, 2021): Phase I/II – HPV-Positive Cancers (HB-201/HB-202)
70 Figure 22: Penpulimab for Nasopharyngeal Cancer (September 16, 2021): Phase II – NPC (China)
73 Figure 23: Multikine for Head and Neck Cancer (June 28, 2021): Phase III – IT-MATTERS
74 Figure 24: Toripalimab for Nasopharyngeal Cancer (June 3, 2021): Phase III – JUPITER-02
76 Figure 25: Tislelizumab for Nasopharyngeal Cancer (May 21, 2021): Phase III – RATIONALE 309 (China)
78 Figure 26: Ficlatuzumab for Head and Neck Cancer (May 19, 2021): Phase II – w/wo Cetuximab (University of Arizona)
82 Figure 27: mRNA-4157 for Head and Neck Cancer (November 11, 2020): Phase I – KEYNOTE-603 (w/Pembrolizumab)
84 Figure 28: Toripalimab for Nasopharyngeal Cancer (September 28, 2020): Phase III – JUPITER-02
85 Figure 29: Bavencio for Head and Neck Cancer (September 19, 2020): Phase III – JAVELIN HEAD AND NECK 100
89 Figure 30: Imfinzi for Head and Neck Cancer (May 29, 2020): Phase II – CheckRad-CD8 (w/Tremelimumab)
91 Figure 31: NBTXR3 (Drug) for Head and Neck Cancer (May 29, 2020): Phase I – Study-1100 (w/Nivolumab or Pembrolizumab)
93 Figure 32: Tipifarnib (Oncology) for Head and Neck Cancer (May 29, 2020): Phase II – RUN-HN (HRAS Mutations)
94 Figure 33: 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
45 Table 10: Pipeline drugs for nasopharyngeal cancer in the US
64 Table 11: Historical global sales, by drug ($m), 2016–20
65 Table 12: Forecasted global sales, by drug ($m), 2021–25
66 Table 13: HB-201 for Head and Neck Cancer (November 9, 2021)
69 Table 14: Penpulimab for Nasopharyngeal Cancer (September 16, 2021)
71 Table 15: Opdivo for Head and Neck Cancer (July 16, 2021)
72 Table 16: Multikine for Head and Neck Cancer (June 28, 2021)
73 Table 17: Toripalimab for Nasopharyngeal Cancer (June 3, 2021)
75 Table 18: Tislelizumab for Nasopharyngeal Cancer (May 21, 2021)
76 Table 19: Ficlatuzumab for Head and Neck Cancer (May 19, 2021)
79 Table 20: Feladilimab for Head and Neck Cancer (April 14, 2021)
80 Table 21: Imfinzi for Head and Neck Cancer (February 5, 2021)
81 Table 22: mRNA-4157 for Head and Neck Cancer (November 11, 2020)
83 Table 23: Toripalimab for Nasopharyngeal Cancer (September 28, 2020)
84 Table 24: Bavencio for Head and Neck Cancer (September 19, 2020)
86 Table 25: SNS-301 for Head and Neck Cancer (September 18, 2020)
87 Table 26: ALX148 for Head and Neck Cancer (May 29, 2020)
88 Table 27: Imfinzi for Head and Neck Cancer (May 29, 2020)
90 Table 28: NBTXR3 (Drug) for Head and Neck Cancer (May 29, 2020)
92 Table 29: Tipifarnib (Oncology) for Head and Neck Cancer (May 29, 2020)
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