Disease Analysis: Head and Neck Cancer
Author: David Dahan
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, a type of HNSCC, is widespread in East Asia but comparatively rare in Western nations.
- Most HNSCC patients are treated with surgery, radiotherapy (RT), and/or platinum-based chemotherapy.
- Erbitux, once among the dominant branded systemic therapies for HNSCC, is being eclipsed by newer checkpoint inhibitors. Erbitux is approved for use in combination with RT to treat patients with locally or regionally advanced HNSCC, in combination with chemotherapy for first-line recurrent/metastatic HNSCC, and as monotherapy for second-line recurrent/metastatic HNSCC.
- ASP-1929 is a cetuximab antibody conjugated to an infrared dye and is used in combination with light delivered through a fiber-optic catheter. The antibody-drug conjugate has received approval in Japan (where it is marketed as Akalux) based on Phase II results. A Phase III trial, LUZERA-301, is enrolling third-line or later, unresectable, locoregional HNSCC patients, and has an estimated primary completion date of September 2024.
- 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.
- Bempegaldesleukin (BEMPEG) consists of recombinant IL-2 conjugated to polyethylene glycol. A Phase II/III trial, PROPEL-36, is comparing BEMPEG + Keytruda to Keytruda alone in first-line treatment of recurrent/metastatic HNSCC patients with PD-L1-expressing tumors.
- 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 HNSCC, where the average probability a drug candidate advances from Phase III is 23.8%, significantly lower than the average of 47.3% 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 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. Another drug being developed for locally advanced HNSCC is NBTXR3, a radioenhancer that is injected intratumorally and amplifies the radiation dose during RT. A Phase III trial, NANORAY-312, is comparing NBTXR3 + RT ± Erbitux versus RT ± Erbitux. The trial is enrolling high-risk, chemotherapy-ineligible elderly patients with locally advanced 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 third-line or later nasopharyngeal cancer, with an approval decision due during early 2022
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
41 Nasopharyngeal cancer
46 KEY REGULATORY EVENTS
46 Rx For Immuno-Oncology Excess? Top US FDA Cancer Officials Take On Development ‘Wild West’
46 Nasopharyngeal Cancer Is US Opening Act For Toripalimab, Penpulimab
46 China Inc. Shines In Latest Batch Of Approvals
47 Look East For New Checkpoint Inhibitors
47 Additional Keytruda Indication Among Latest China Approvals
48 PROBABILITY OF SUCCESS
49 LICENSING AND ASSET ACQUISITION DEALS
49 AstraZeneca Ends Collaboration With Inovio For Cancer Immunotherapy
49 GSK Spends Heavily On iTeos’ TIGIT To Build A New IO Cornerstone
49 LianBio Licenses Cancer Radioenhancer From Nanobiotix
49 Shepherd Signs Oncology Alliances With Mayo, NCATS
50 Merck KGaA Bags Exclusive Rights To Develop, Sell Debiopharm’s Xevinapant
50 Nektar Finances Trial Via Capital, Collaboration With SFJ
51 CLINICAL TRIAL LANDSCAPE
52 Sponsors by status
53 Sponsors by phase
54 Recent events
56 DRUG ASSESSMENT MODEL
60 MARKET DYNAMICS
61 FUTURE TRENDS
61 Keytruda combined with chemotherapy is the new standard of care for first-line recurrent/metastatic HNSCC
61 Chemotherapy-free regimens continue to be developed for metastatic first-line patients
62 New options are being developed for second-line recurrent/metastatic HNSCC
62 Toripalimab combined with chemotherapy is set to become the new standard of care for advanced recurrent or metastatic NPC
62 Therapies are being developed for locally advanced disease
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)
87 KEY UPCOMING EVENTS
87 Head and neck cancer
87 Nasopharyngeal cancer
89 KEY OPINION LEADER INSIGHTS
90 BIBLIOGRAPHY
91 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
41 Figure 7: Overview of pipeline drugs for nasopharyngeal cancer in the US
41 Figure 8: Pipeline drugs for nasopharyngeal cancer, by company
42 Figure 9: Pipeline drugs for nasopharyngeal cancer, by drug type
42 Figure 10: Pipeline drugs for nasopharyngeal cancer, by classification
48 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
60 Figure 19: Market dynamics in head and neck cancer
61 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
87 Figure 30: Key upcoming events in head and neck cancer
88 Figure 31: Key upcoming events in nasopharyngeal 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
43 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), 2022–26
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)
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