NCCN Guidelines for Head and Neck Cancers V.1.

2022 – Interim on 10/15/21

Guideline Page Institution Vote

Panel Discussion/References
and Request YES NO ABSTAIN ABSENT
OR-3 Based on the discussion, the panel consensus supported 21 0 0 10
Internal request: including concurrent systemic therapy/RT as an option for
those selected patients with stage T4a oral cancer who
Comment to consider including concurrent decline surgery.
systemic therapy/RT as an option for selected
patients with stage T4a oral cancer who decline
surgery.

NASO-2/NASO-3 Based on the discussion, the panel consensus supported

Internal request: the following primary treatment options for nasopharynx
cancer, by stage:
Comment to consider further separating • T2, N0, M0:
treatment recommendations for nasopharynx o Definitive RT
o Definitive RT + concurrent systemic therapy if 18 2 1 10
cancer by the following clinical stages:
high-risk features (bulky tumor volume, high 20 0 1 10
• T2, N0, M0
serum EBV DNA copy number)
• T1-2, N1, M0 or T3, N0, M0
• T3-4, N1-3, M0 or Any T, N2, M0
• T1–2,N1,M0 or T3,N0:
• T1-4, N0-3, M1 o Concurrent systemic therapy/RT
19 1 1 10
o Consider induction chemotherapy if high-risk
features (bulky tumor volume, high serum EBV 18 1 2 10
DNA copy number)
o Consider adjuvant chemotherapy if high-risk 20 0 1 10
features (bulky tumor volume, high serum EBV
DNA copy number)

• T3-4,N1-3,M0 or any T,N2-3,M0:

o Induction chemotherapy followed by systemic 19 0 2 10
therapy/RT
 This is a category 1, preferred 15 1 5 10
recommendation.
o Concurrent systemic therapy/RT followed by 19 1 1 10
adjuvant chemotherapy

o Concurrent systemic therapy/RT (category 3) 8 11 2 10

NCCN Guidelines for Head and Neck Cancers V.1.2022 – Interim on 10/15/21

Guideline Page Institution Vote

Panel Discussion/References
and Request YES NO ABSTAIN ABSENT
NASO-2/NASO-3 (continued) • T1-4, N0-3, M1
o Oligometastatic disease
 Systemic therapy (if PS 0-1) followed 20 0 1 10
by RT
 Systemic therapy (if PS 0-1) followed
18 2 1 10
by cisplatin/RT 18 2 1 10
 Systemic therapy (if PS 0-2) 19 1 1 10
 Systemic therapy (if PS 0-2) followed 17 3 1 10
by RT, if CR or near CR
 Concurrent cisplatin + RT (if PS 0-1)
o Widely metastatic and Good PS (0-2)
 Systemic therapy
20 0 1 10
 Systemic therapy + consider RT if CR 19 1 1 10
or near CR
o Widely metastatic and Poor PS (3-4) 19 0 2 10
 Best supportive care
NASO-B The panel consensus supported clarifying that 17 0 4 10
Internal request: gemcitabine/cisplatin is a category 1 recommendation for
EBV-associated disease, category 2A for non-EBV-
associated disease.
Comment to consider clarifying that
gemcitabine/cisplatin is a category 1
induction/sequential systemic therapy
recommendation for EBV-associated disease.

NASO-B The panel consensus was to remove 13 0 8 10

Internal request: cisplatin/epirubicin/paclitaxel from the other recommended
induction/sequential systemic therapy options for
Comment to consider removing nasopharynx cancer.
cisplatin/epirubicin/paclitaxel from the other
recommended induction/sequential systemic
therapy options for nasopharynx cancer.
NCCN Guidelines for Head and Neck Cancers V.1.2022 – Interim on 10/15/21
Guideline Page
and Request
NASO-B
Internal request:
Comment to consider adding the following
systemic therapy/RT followed by adjuvant
chemotherapy option for nasopharynx cancer
based on recent data: Cisplatin + RT followed by
capecitabine (for T4, N1-3 or any T, N2-3)
NASO-B
Internal request:
Comment to consider adding the following
platinum-based regimens as options for those
with nasopharynx cancer being treated with
reirradiation + concurrent systemic therapy:
• Cisplatin
• Carboplatin (if cisplatin
ineligible/intolerant)
Institution Vote
Panel Discussion/References
YES NO ABSTAIN ABSENT
The panel consensus supported the addition of cisplatin + 14 3 4 10
RT followed by capecitabine for T4, N1-3 or any T, N2-3
nasopharynx cancer. This is a category 2B, other
recommended regimen.
Reference:
Chen YP, Liu X, Zhou Q, et al. Metronomic capecitabine as
adjuvant therapy in locoregionally advanced
nasopharyngeal carcinoma: A multicentre, open-label,
parallel-group, randomised, controlled, phase 3 trial. Lancet
2021;398:303-313.
The panel consensus supported adding the following
platinum-based regimens as options for those with
nasopharynx cancer being treated with reirradiation +
concurrent systemic therapy:
• Cisplatin 20 0 1 10
• Carboplatin (if cisplatin ineligible/intolerant) 18 1 2 10
These are category 2A recommendations.
References:
• Kong F, Zhou J, Du C, et al. Long-term survival and
late complications of intensity-modulated radiotherapy
for recurrent nasopharyngeal carcinoma. BMC Cancer
2018;18:1139.
• Lee VHF, Kwong DL, Leung T-W, et al.
Hyperfractionation compared to standard fractionation
in intensity-modulated radiation therapy for patients
with locally advanced recurrent nasopharyngeal
carcinoma. Eur Arch Otorhinolaryngol 2017;274:1067-
1078.
NCCN Guidelines for Head and Neck Cancers V.1.2022 – Interim on 10/15/21
Guideline Page
and Request
NASO-B
Internal request:
Comment to consider adding
cisplatin/gemcitabine + PD-1 inhibitor (eg,
pembrolizumab or nivolumab) as an option for
recurrent, unresectable, oligometastatic,
metastatic nasopharynx cancer.
SALI-B
External request:
Submission from Daiichi Sankyo, Inc. on
06/11/21 to consider adding “fam-trastuzumab
deruxtecan-nxki” under HER2 targeted therapy
for HER2+ salivary gland tumors.
Institution Vote
Panel Discussion/References
YES NO ABSTAIN ABSENT
The panel consensus supported adding the following
options for recurrent, unresectable, oligometastatic,
metastatic nasopharynx cancer:
• Cisplatin/gemcitabine + pembrolizumab 14 2 5 10
o This is a category 2A, other recommended
regimen.
• Cisplatin/gemcitabine + nivolumab 12 2 7 10
o This is a category 2A, other recommended
regimen.
References:
• Yang Y, Qu S, Li J, et al. Camrelizumab versus placebo
in combination with gemcitabine and cisplatin as first-
line treatment for recurrent or metastatic
nasopharyngeal carcinoma (captain-1st): A multicentre,
randomised, double-blind, phase 3 trial. Lancet Oncol
2021;22:1162-1174.
• Mai H-Q, Chen Q-Y, Chen D, et al. Toripalimab or
placebo plus chemotherapy as first-line treatment in
advanced nasopharyngeal carcinoma: A multicenter
randomized phase 3 trial. Nat Med 2021;27:1536-1543.
Based on the review of the data, the panel consensus was 7 6 8 10
to include fam-trastuzumab deruxtecan-nxk as an option for
recurrent, unresectable or metastatic HER2+ salivary gland
tumors. This is a category 2B, useful in certain
circumstances recommendation.
Reference:
• Bando H, Kinoshita I, Modi S, et al. Trastuzumab
deruxtecan (T-DXd) in patients with human epidermal
growth factor receptor 2 (HER2)-expressing salivary
duct carcinoma: Subgroup analysis of two phase 1
studies. J Clin Oncol 39, 2021 (suppl 15; abstr 6079).
NCCN Guidelines for Head and Neck Cancers V.1.2022 – Interim on 10/15/21

Guideline Page Institution Vote

Panel Discussion/References
and Request YES NO ABSTAIN ABSENT
SALI-B Based on a review of the data, the panel consensus
Internal request: supported adding the following systemic therapy options for
recurrent, unresectable, metastatic salivary gland tumors:
• Paclitaxel
Comment to consider adding the following o This is a category 2A, other recommended
systemic therapy options for recurrent, regimen for non-adenoid cystic carcinoma
(ACC) 14 1 6 10
unresectable, metastatic salivary gland tumors:
o This is a category 2B, other recommended
regimen for ACC 10 4 7 10
• Paclitaxel
• Carboplatin/paclitaxel • Carboplatin/paclitaxel
• Carboplatin/gemcitabine o This is a category 2A, other recommended
regimen for non-adenoid cystic carcinoma 17 0 4 10
(ACC)
o This is a category 2A, other recommended
regimen for ACC
• Carboplatin/gemcitabine 15 2 4 10
o This is a category 2A, other recommended
15 2 4 10
regimen
References:
• Gilbert J, Li Y, Pinto HA, et al. Phase II trial of taxol in
salivary gland malignancies (E1394): a trial of the
Eastern Cooperative Oncology Group. Head Neck.
2006;28:197-204.
• Nakano K, Sato Y, Sasaki T, et al. Combination
chemotherapy of carboplatin and paclitaxel for
advanced/metastatic salivary gland carcinoma patients:
differences in responses by different pathological
diagnoses. Acta Otolaryngol. 2016;136:948-51.
• Airoldi M, Fornari G, Pedani F, et al. Paclitaxel and
carboplatin for recurrent salivary gland malignancies.
Anticancer Res. 2000;20:3781-3.
• Laurie SA, Siu LL, Winquist E, et al. A phase 2 study of
platinum and gemcitabine in patients with advanced
salivary gland cancer: a trial of the NCIC Clinical Trials
Group. Cancer. 2010;116:362-8.
NCCN Guidelines for Head and Neck Cancers V.1.2022 – Interim on 10/15/21
Guideline Page
and Request
ADV-2/ADV-4
Internal request:
Comment to clarify that treatment with an
alternate single-agent systemic therapy is an
option for those with metastatic disease (PS 2), if
persistent disease/progression after primary
treatment with single-agent systemic therapy.
SYST-A (1 of 4)
Internal request:
Comment to reassess the data for weekly
cisplatin as a primary systemic therapy +
concurrent RT option for non-nasopharyngeal
head and neck cancers.
Institution Vote
Panel Discussion/References
YES NO ABSTAIN ABSENT
The panel consensus supported clarifying that treatment 21 0 0 10
with an alternate single-agent systemic therapy is an option
for those with metastatic disease (PS 2), if persistent
disease/progression after primary treatment with single-
agent systemic therapy.
Based on the review of the data, the panel consensus 17 3 1 10
supported the continued listing of weekly cisplatin as a
primary systemic therapy + concurrent RT option for non-
nasopharyngeal head and neck cancers, with a change in
category from a category 2B to a category 2A
recommendation.
References:
• Beckmann GK, Hoppe F, Pfreundner L, Flentje MP.
Hyperfractionated accelerated radiotherapy in
combination with weekly cisplatin for locally advanced
head and neck cancer. Head Neck 2005;27:36-43.
• Medina JA, Rueda A, de Pasos AS, et al. A phase II
study of concomitant boost radiation plus concurrent
weekly cisplatin for locally advanced unresectable head
and neck carcinomas. Radiother Oncol 2006;79:34-38.
NCCN Guidelines for Head and Neck Cancers V.1.2022 – Interim on 10/15/21
Guideline Page
and Request
SYST-A (2 of 4)
External request:
Submission from Bristol Myers Squibb on
09/20/21 to consider the addition of nivolumab
and ipilimumab as a Category 2A recommended
first-line treatment option for R/M SCCHN with
combined positive score (CPS) ≥ 1 and CPS ≥
20.
SYST-A (2 of 4)
Internal request:
Comment to consider adding
cetuximab/pembrolizumab as an option for
recurrent, unresectable, or metastatic non-
nasopharyngeal head and neck cancers.
Institution Vote
Panel Discussion/References
YES NO ABSTAIN ABSENT
Based on the review of the data, the panel consensus did 8 10 3 10
not support the addition of nivolumab and ipilimumab as a
first-line treatment option for R/M SCCHN with combined
positive score (CPS) ≥ 1 and CPS ≥ 20, due to limited
available data.
Reference:
Argiris A, Harrington K, Tahara M, et al. Nivolumab +
ipilimumab vs EXTREME regimen as first-line treatment for
recurrent/metastatic squamous cell carcinoma of the head
and neck: final results of CheckMate 651. Oral presentation
at: 2021 European Society for Medical Oncology Congress;
September 16-20, 2021; Virtual Meeting.
Based on the review of the data, the panel consensus 11 6 4 10
supported the addition of cetuximab/pembrolizumab as an
option for recurrent, unresectable, or metastatic non-
nasopharyngeal head and neck cancers. This is a category
2B, useful in certain circumstances recommendation.
Reference:
• Sacco AG, Chen R, Worden FP, et al Pembrolizumab
plus cetuximab in patients with recurrent or metastatic
head and neck squamous cell carcinoma: an open-
label, multi-arm, non-randomised, multicentre, phase 2
trial. Lancet Oncol. 2021 Jun;22(6):883-892.
NCCN Guidelines for Head and Neck Cancers V.1.2022 – Interim on 10/15/21

Guideline Page Institution Vote

and Request
SYST-A (2 of 4)
Internal request:
Comment to reassess the data for
pembrolizumab/platinum (cisplatin or
carboplatin)/docetaxel as an option for recurrent,
unresectable, or metastatic non-nasopharyngeal
head and neck cancers.
Panel Discussion/References
YES NO ABSTAIN ABSENT
Based on a review of the data, the panel consensus 17 2 2 10
supported the continued listing of pembrolizumab/platinum
(cisplatin or carboplatin)/docetaxel as an option for
recurrent, unresectable, or metastatic non-nasopharyngeal
head and neck cancers, with a change in category from a
category 2B to a category 2A recommendation.
References:
• Burtness B, Harrington KJ, Greil R, et al.
Pembrolizumab alone or with chemotherapy versus
cetuximab with chemotherapy for recurrent or
metastatic squamous cell carcinoma of the head and
neck (KEYNOTE-048): a randomised, open-label,
phase 3 study. Lancet 2019;394:1915-1928.
• Samlowski WE, Moon J, Kuebler JP, et al. Evaluation
of the combination of docetaxel/ carboplatin in patients
with metastatic or recurrent squamous cell carcinoma
of the head and neck (SCCHN): a Southwest Oncology
Group Phase II study. Cancer Invest 2007;25:182-188.