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2017 Evolving Strategies sin HNSCC

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The Evolving Treatment Algorithm for Advanced
Head & Neck Squamous Cell Cancer
Jan B. Vermorken, MD, PhD
Department of Medical Oncology
Antwerp University Hospital
Edegem, Belgium
prIME Oncology Meeting, Madrid, Spain, September 10, 2017
Head & Neck Cancer
Epidemiology, Risk Factors, & Presentation
• 5%-6% of all cancers (688,000 new cases in 2012; 350,000 deaths)
• ≥50% are ≥60 years of age; >90% squamous type (Western world)
• Risk factors:
– Tobacco smoking
− Poor oral health
– Alcohol use
− Mechanical irritation
– Betel chewing
− Occupational exposure
– HPV
− Malnutrition
• Localized disease 40%, regional metastases 50%, distant metastases 10%
• 2/3 locally/regionally advanced
• Major threat: Local recurrence, SPT, SFT
HPV, human papillomavirus; SFT, second field tumor; SPT, second primary tumor
Milestones in Head & Neck Cancer Management
MARCH
MACH-NC
19th century
Surgery
1900
1950s
RT
CT
X-rays
1970s
1980s
Laser
ASCO
CT scan 1982
MRI
1990s
PET
2000s
Targeted
therapies
2010 2014
TORS
IT
MARCH, meta-analysis of radiotherapy in squamous cell carcinomas of head and neck; MACH-NC, meta-analysis of chemotherapy in head and neck cancer;
RT, radiotherapy; CT, chemotherapy; PET, positron emission tomography; TORS, Trans-oral robotic surgery; IT, immunotherapy
Modified from Jean-Louis Lefebvre (with permission)
Milestones in Systemic Therapies (± RT) in
Head & Neck Squamous Cell Cancer (HNSCC)
1960s
Single-agent chemotherapy
Methotrexate
1970s
Combination chemotherapy regimens
Platinum compounds
1980s
Induction chemotherapy
Larynx preservation
1990s
Concurrent chemoradiotherapy (CCRT) standard
Taxanes
2000s
Induction chemotherapy revisited
Targeted therapy
Immunotherapy
Important Recent Findings
• HPV is a risk factor for OPC (a growing epidemic)
• Tumor HPV single strongest predictor of survival (OPC)
• EGFR is a second prognostic marker
• Anti-EGFR medication is getting major attention
• Expanded role of chemotherapy (CCRT, ICT)
• Revival of immunology/immunotherapy
• Improved irradiation techniques available (IMRT)
• New imaging techniques available (PET)
• Quality of life of survivors is getting more attention
EGFR, epidermal growth factor receptor; ICT, Induction chemotherapy; IMRT, intensity modulated radiotherapy; OPC, oropharyngeal cancer
The Prognostic Significance of HPV in OPC
100
88 Had HPVnegative tumors
178 Had HPVpositive tumors
88 Had ≤10
pack-years
90 Had >10
pack-years
23 Had ≤10
pack-years
65 Had >10
pack-years
Overall Survival (%)
266 patients with oropharyngeal cancer, known tumor
HPV status and known number of pack years of smoking
Low risk
75
Intermediate risk
50
High risk
25
0
26 Had
N0-N2a
cancer
114 of 266 (42.9%) were
at low risk
64 Had
N2b-N3
cancer
26 Had
T2-T3
tumors
76 of 266 (29.7%) were
at intermediate risk
8 Had
T4
tumors
73 of 266 (27.4%) were
at high risk
0
1
2
3
4
5
95
44
28
46
24
8
Years Since Randomization
No at Risk
Low risk
114
Intermediate risk 79
High risk
73
111
70
52
106
64
43
102
54
33
The 3-year rates of overall survival were 93.0% (95% CI, 88.3 to 97.7) in the low-risk group,
70.8% (95% CI, 60.7 to 80.8) in the intermediate-risk group,
and 46.2% (95% CI, 34.7 to 57.7) in the high-risk group.
Ang KK, et al. N Engl J Med. 2010;363(1):24-35.
Multidisciplinary Team (MDT) Meetings
Head and
neck surgeon
Biologist,
pathologist
Medical
oncologist
Patient
Speech
therapist
Radiologist
Guidelines
Radiation
oncologist
Anesthesiologist,
internist, general
practitioner
Oncologic
dentist
Physical therapist, dietitian,
social worker, psychologist,
psychiatrist
Clinical trials
Decision Making During MDT Meetings
HNSCC Patients
• Disease factors (eg, site, stage, biology [HPV, EGFR], specific risk factors for
locoregional or distant relapse)
• Patient factors (eg, age, sex, performance status, nutritional status, comorbid
chronic disease, oral health, lifestyle habits, socio-economic status)
• Treatment factors (surgery, radiotherapy, chemotherapy, immunotherapy,
targeted therapy)
• What do patients want?
Clinical Practice Guidelines for Patients With
Locoregionally Advanced HNSCC
Standard Options
Level of
evidence
Grade of
recommendation
Surgery  RT or CCRT
I
A
Concomitant CT and RT*
I
A
Cetuximab plus RT
II
B
CCRT or ICT  RT for
organ preservation
II
A
ICT  CCRT (sequential
therapy)
Still under evaluation
*In case of mutilating surgery and in nonresectable disease; Cisplatin dose: 100 mg/m2 x3 during CCRT
Grégoire V, et al. Ann Oncol. 2010:21(Suppl 5):vI84-vI86.
Methods to Reduce the Toxicity of CisplatinBased CCRT in HNSCC: Treatment Factors
Better targeting of RT
• CT – MRI – (PET)
• IGRT
New radiotherapy techniques
• IMRT and SW-IMRT
• Stereotactic radiotherapy
• IMPT
Alternatives for high-dose 3-weekly cisplatin
• Other cisplatin dose or schedules
• Other cytotoxics (carboplatin, taxanes, low-dose gemcitabine)
• Biological agents (cetuximab)
• Hypoxic modification (nimorazole)
CT, computed tomography; IGRT, image-guided RT; IMPT, intensity-modulated particle therapy; MRI, magnetic resonance imaging; SW-IMRT, swallowing sparing
intensity modulated RT
Relapsing HNSCC: Heterogenous Group (1)
• Type of relapse
− Local and/or regional only
− Metastatic only
− Both
• Type of primary therapy
− Single modality (S or RT)
− Combined modality (S→LT*, CCRT, BRT, ICT→LT*)
• Interval between primary treatment and relapse:
− Short interval (<6 months) after CCRT → poor prognosis
BRT, RT + cetuximab; ICT, induction chemotherapy LT, local therapy (ie. RT, CCRT or BRT); S, surgery
100
100
80
80
Survival (%)
Survival (%)
Relapsing HNSCC: Heterogenous Group (2)
Influence of p16 status
60
40
20
0.5
40
20
p16 positive
p16 negative
0
60
1.0
1.5
2.0
p16 positive
p16 negative
0
0.5
Time Since Progression (years)
57
43
51
28
41
16
40
14
38
12
48
33
100
100
80
80
60
40
20
0.5
1.0
1.5
29
20
28
16
Fakhry C, et al. J Clin Oncol. 2014;32(30):3365-3373.
22
10
21
9
31
18
20
11
20
7
13
7
1.0
1.5
2.0
40
2.0
p16 positive
p16 negative
0
0.5
Time Since Progression (years)
No. at risk
p16 positive
p16 negative
2.0
60
20
p16 positive
p16 negative
0
1.5
Time Since Progression (years)
No. at risk
p16 positive
p16 negative
Survival (%)
Survival (%)
No. at risk
p16 positive
p16 negative
1.0
Time Since Progression (years)
21
9
No. at risk
p16 positive
p16 negative
76
56
54
30
39
17
39
12
30
10
•
Standard Treatment Options in
Recurrent/Metastatic-HNSCC
2017
Resectable disease
− Surgery at all times if possible
− Post-op RT or CCRT (if not complete)1
• Nonresectable disease
− RT or CCRT (if no organ dysfunction/morbidity)1
• Recurrent/metastatic disease
− First-line: EXTREME (platinum/5-FU/cetuximab)2,3
Alternatives in unfavorable patients: single agents ± cetuximab
− Second-line: CheckMate-141 (nivolumab single agent)3
Pembrolizumab also approved for same indication3
− Best supportive care only (performance status 3)2,3
1. Strojan P, et al. Head Neck. 2015;37(1):134-150. 2. Grégoire V, et al. Ann Oncol. 2010:21(Suppl 5):vI84-vI86. 3. National Comprehensive Cancer Network.
NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Available at: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf.
Accessed August 31, 2017.
Unmet Needs in Head & Neck Cancer
• Customized treatment guidelines
• Noninvasive diagnostic tools
• Better understanding of pathways that drive head and neck cancer or
drug resistance
• Adjuvant treatment of intermediate/high-risk HNSCC patients
• Predictive markers
• Supportive care needs of long-term HNSCC survivors
• More information and healthcare services to caregivers
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