understanding recent progress in head and neck squamous cell carcinoma

Understanding Recent Progress in Head and Neck Squamous Cell

CarcinomaMaura L. Gillison, MD, PhD

Professor of MedicineThe Ohio State University

Comprehensive Cancer Center

Dr. Gillison discloses the following commercial relationships: Consultant: Amgen, AstraZeneca, Celgene,

Bristol-Myers Squibb, Lilly, Merck, GlaxoSmithKline

Disclosures

Describe the diagnostic evaluation and staging of HNSCC

Evaluate prognostic markers that can optimize treatment selection for patients with locally advanced and recurrent/metastatic HNSCC

Assess efficacy and safety data on novel therapies for patients with locally advanced and recurrent/metastatic HNSCC

HNSCC = head and neck squamous cell carcinoma.

Learning Objectives

NCI, 2012.

Head and Neck Cancer

Paranasal sinusNasopharynxOral cavityPharynx

OropharynxHypopharynxLarynx

Salivary glands

Worldwide 2012:→ 599,000 cases worldwide in 2012→ 325,000 deaths worldwide in 2012

US 2016:→ 61,760 cases→ 13,190 deaths

Ferlay et al, 2015; ACS, 2016.

Head and Neck Cancer Burden

Gillison, 2013.

Global Incidence in 2012

Tobacco use Alcohol use HPV Oral hygiene Diet Family history Age, gender, race

HPV = human papillomavirus.Gillison, 2007.

Established Risk Factors

Population Attributable Risk (PAR), Oral Cancer, France

Risk Factor PARa (%) 95% CIAlcohol alone 0.3 -3.0-3.9

Tobacco alone 12.7 6.9-18.0Tobacco and alcohol 69.9 64.4-74.7

Tobacco and/or alcohol 82.9 73.8-88.5

Adjusted for gender, age, BMI, education, exercise, family history of HNC, alcohol, residence, history of candidiasis, tea drinking.

CI = confidence interval; BMI = body mass index; HNC = head and neck cancer. Radoi et al, 2015.

Tobacco Use

Unique Characteristics of HPV-HNC

BOT = base of tongue; SE = socioeconomic.Gillison et al, 2008.

HPV-Positive HPV-NegativeAnatomic siteHistologyAge GenderSE statusRisk factorsCofactorsGeneticsIncidenceSurvival

Tonsil/BOTBasaloidYounger3:1 men

HighSexual behavior

Marijuana, immunosuppression

p53WT, p16+Increasing

High

All sites Keratinized

Older3:1 men

LowAlcohol/tobaccoDiet, hygienep53Mu, p16-Decreasing

Worse

In US from 1988 to 2004:

Similar changes in numerous developed countries worldwide

Rapidly Changing Incidence of HPV-Positive vs HPV-Negative

HNC Oropharynx rates

increasing overall HPV-positive increased

by 225% HPV-negative declined

by 50%

Chaturvedi et al, 2011; Chaturvedi et al, 2013.

Oral pain or sore throat Ulcer or mass Dysphagia or odynophagia Hoarseness Dyspnea Headache or ear pain Sinus congestion or bleeding Neck mass

NCCN, 2016.

Common Presenting Symptoms

Physical exam Indirect laryngoscopy Imaging studies Panendoscopy with biopsy Fine needle aspiration Chest imaging PET scan

PET = positron emission tomography.

Head and Neck Cancer Staging

New staging system specific to HPV-positive oropharynx cancer went into effect January 1, 2017

It has not yet been released, but is based upon an analysis published by O’Sullivan and colleagues (2016)

TNM = extent of tumor, extent of spread to lymph nodes, presence of metastasis.O’Sullivan et al, 2016.

8th Edition AJCC TNM Staging System

Tumor stage T1: Tumor ≤2 cm T2: Tumor >2 cm and ≤4 cm T3: Tumor >4 cm T4: Tumor invades adjacent structures

Edge et al, 2010.

7th Edition AJCC TNM Staging System: Oropharynx Cancer

Edge et al, 2010.

TNM Staging: Cervical Lymph Nodes

Edge et al, 2010.

7th Edition AJCC TNM Staging System: Oropharynx Cancer

StageStage 1 T1N0Stage 2 T2N0Stage 3 T3N0, T1-3N1Stage 4A T1-4N2, resectableStage 4B T1-4N0-3,

“unresectable”Stage 4C Any T, Any N, M1

HPV-positive OPC HPV-negative OPC

TNM stage discriminates prognostic groups for HPV-negative but not HPV-positive oropharynx cancer.

76 68 53 45 34

5-year OS5-year OS8882848160

OS = overall survival; OPC = oropharyngeal cancer. O’Sullivan et al, 2016.

7th Edition AJCC Staging System: OS

5-year OS

7th Edition AJCC ICON-S

None N0 N0Unilateral N1, N2a, N2b N1Bilateral N2c N2>6 cm N3 N3

ICON-S = International Collaboration on Oropharyngeal Cancer Network for Staging. O’Sullivan et al, 2016.

ICON-S Proposal for HPV-Positive HNC

8th Edition AJCC Staging

Associations between ICON-S stage and OS in training (left) and validation (right) data

sets.76 68 53 45 34

5-year OS5-year OS88828481605-year OS

857853

5-year OS888165

AHR = adjusted hazard ratio. O’Sullivan et al, 2016.

ICON-S Proposal for HPV-Positive HNC

8th Edition AJCC Staging (cont.)

Age Race Performance status Comorbidity HPV status Weight loss Anemia Smoking status Social support

Prognostic Factors

Arm 1:Standard fractionation (SFX) 70 Gy/35 Fx/7 weeksplus cisplatin 100 mg/m2 on D 1, 22, 43

RANDOMIZE

Tumor Site1. Larynx2. Non-larynxS

TRATIFY

Nodal Stage1. N02. N1 or N2a-b3. N2c or N3Zubrod Performance

Status1. 02. 1

Arm 2:Accelerated Fractionation by Concomitant Boost (AFX-C)72 Gy/42 Fx/6 weeksplus cisplatin 100 mg/m2 on D 1, 22

Ang et al, 2010.

Radiation Therapy Oncology Group 0129

Ang et al, 2010.

RTOG 0129 OS by HPV Status

log-rank p<0.001

3-year difference26%, 12-40

Ove

rall S

urviv

al (%

)

0

25

50

75

100

Years after Randomization0 1 2 3 4 5

Patients atRiskHPV Pos.HPV Neg.

Patients atRisk

206117

Patients atRisk

19389

Patients atRisk

18076

Patients atRisk

16264

Patients atRisk

11934

Patients atRisk

309

HPV Positive

HPV Negative

Ang et al, 2010.

HPV Status and Survival

HR = hazard ratio. Ang et al, 2010.

Risk Model for Death and Progression: Oropharynx Cancer

New Data From Surgical Trials

Arm 2 (C+RT) N=282

PET-CT at 12 weeks

Eligibility Oral cavity,

oropharynx, larynx, hypopharynx, unknown primary

N2 or N3 Suitable for

chemoRT No neck dissection

contraindications No prior treatment Age ≥18 years

C = chemotherapy; RT = radiation therapy; CT = computed tomography. Mehanna et al, 2016.

PET-NECK Noninferiority Trial

Arm 1 (C+RT) N=282

Planned neck dissection

1:1

90% power, 2-year OS 75% , Δ<10%, HR<1.5

Primary End Point: OS

RANDOMIZE

PET-NECK: Patients Characteristics

Mehanna et al, 2016.

2-year OS 84.9% vs 81.5%, HR 0.92, (95% CI 0.65-1.32)Mehanna et al, 2016.

PET-CT Surveillance vs Neck Dissection in Advanced HNC

PET-CT reduced neck dissections (54 vs 221)

Surgical complications were similar OS was similar Quality of life was similar PET-CT was cost effective

Mehanna et al, 2016.

PET-CT Surveillance vs Neck Dissection in Advanced HNC

(cont.)

Arm 2 N=255Surveillance

Elective vs Therapeutic Neck Dissection in Node-Negative Oral

CancerEligibility SCC oral cavity Lateralized T1-

2 N0 No history of

HNC No prior

treatment Age 18-75

years

Arm 1 N=245

Planned neck dissection

1:1

80% power, 5-year OS 60% , Δ>0%, HR<1.5

STRATIFY

Tumor siteT1 vs T2Gender+ vs-US

RANDOMIZE

D’Cruz et al, 2015.

Median depth of invasion 6 mm, range 0-20D’Cruz et al, 2015.

ELECTIVE-NECK: Patient Characteristics

Median follow-up 39 months3-year OS 80.0% vs 67.5%

DFS = disease-free survival. D’Cruz et al, 2015.

Elective vs Therapeutic Neck Dissection in Node-Negative Oral Cancer

Median follow-up 39 months3-year DFS 69.5 vs 45.9%


Elective vs Therapeutic Neck Dissection in Node-Negative Oral Cancer (cont.)


Overall Survival According to Subgroup


Pattern of Recurrence

OS and DFS were superior with neck dissection

Depth of invasion predicted node positivity in END arm

Factors associated with worse OS were poor grade, LVE and PNI, higher depth of invasion

Adverse events were similar Study controversial due to undertreatment of

surveillance arm. No RT given to patients with depth of invasion >4 mm

LVE = lymphovascular embolization; PNI = perineural invasion.

Elective vs Therapeutic Neck Dissection in Node-Negative Oral

Cancer

New Data on Induction Chemotherapy for

Nasopharyngeal Cancer

CRT IMRT ≥66 Gy 6-7 weeksCisplatin 100

mg/m2 D 1, 22, 43

Induction Chemotherapy For NPCA

Eligibility WHO II/III NPCA Stage III/IV M0 No prior treatment KPS ≥70 Age 18-59 years Adequate organ

function

NPCA = nasopharyngeal carcinoma; WHO = World Health Organization; KPS = Karnofsky performance status; TPF = cisplatin, fluorouracil, docetaxel; FFS = failure-free survival; CRT = chemoradiotherapy; IMRT = intensity-modulated radiation therapy.Sun et al, 2016.

RANDOMIZE

TPF X 3 N=241

1:1

80% power, 3-year FFS 78%, Δ>10, HR<0.52, N=452

Primary end point: FFS

N=239TPF: Cisplatin 60 mg/m2

Docetaxel 60 mg/m2

5-FU 600 mg/m2/d X4

Variable Subset Induction + CRT CRTGender Men 193 (80%) 174 (73%)

Women 48 (20%) 65 (27%)

Age, years

42 (36-49) 44 (39-50)KPS 90-100 217 (90%) 211 (88%)

70-80 24 (10%) 28 (12%)T category T1 15 (6%) 6 (3%)

T2 27 (11%) 19 (8%)T3 112 (47%) 121 (51%)T4 87 (36%) 93 (39%)

N category N1 97 (40%) 107 (45%)N2 105 (44%) 106 (44%)N3a 13 (5%) 11 (5%)N3b 26 (11%) 15 (6%)

Stage III 129 (54%) 133 (56%)IVA 73 (30%) 80 (33%)IVB 39 (16%) 26 (11%)

Sun et al, 2016.

Patient Characteristics

IC = induction chemotherapy; CCRT = concurrent chemoradiotherapy.Sun et al, 2016.

FFS and OS

Sun et al, 2016.

FFS and OS (cont.)

FFS Induction + CRT CRT HR (95%CI) P ValueNo. failures 52 (22%) 71 (30%) – –3-year FFS 80% (75–85) 72% (66–78) 0.68 (0.48-0.97) 0.034Overall survivalNo. Deaths 26 (11%) 43 (18%) – –3-year OS 92% (87–94) 86% (81–90) 0.59 (0.36-0.95) 0.029Distant FFSDistant failures 27 (11%) 43 (18%) – –3-year DM FFS 90% (86–93) 83% (77–87) 0.59 (0.37–0.96) 0.031Locoregional FFSLR failures 20 (8%) 30 (13%) – –3-year LR FFS 92% (87–95) 89% (84–92) 0.64 (0.36–1.13) 0.12Response rate after CRTOverall 238 (99%) 239 (100%) – –Complete 237 (98%) 232 (97%) – 0.35Partial 1 (<1%) 7 (3%) – –Unassessable 3 (1%) 0 (0%) – –

DM = distant metastasis; LR = locoregional. Sun et al, 2016.

Outcomes Summary

Induction + CRT (n=239) CRT (n=238) P Value

Grade 3 Grade 4 Grade 3 Grade 4 Grade 3 Grade 4Any† 132 (55%) 42 (18%) 125 (53%) 3 (1%) 0·55 <0·0001heme Neutropenia 64 (27%) 37 (15%) 16 (7%) 1 (<1%) <0·0001 <0·0001

Febrile neutropenia 5 (2%) 2 (1%) 0 0 0·061 0·50Neutropenic infection 1 (<1%) 0 0 0 1·00 --Leucopenia 86 (36%) 12 (5%) 40 (17%) 1 (<1%) <0·0001 0·0020Anaemia 4 (2%) 0 5 (2%) 0 0·75 --Thrombocytopenia 5 (2%) 1 (<1%) 2 (1%) 0 0·45 1·00

Non-heme

Stomatitis (mucositis) 96 (40%) 2 (1%) 82 (34%) 2 (1%) 0·20 1·00Vomiting 52 (22%) 4 (2%) 45 (19%) 0 0·44 0·12Nausea 46 (19%) 4 (2%) 40 (17%) 0 0·49 0·12Dry mouth 13 (5%) -- 13 (5%) -- 0·99 --Dermatitis 8 (3%) 1 (<1%) 10 (4%) 0 0·62 1·00Oesophagitis dysphagia or odynophagia

5 (2%) 0 9 (4%) 0 0·27 --

Hepatoxicity 7 (3%) 0 2 (1%) 0 0·18 --Allergic reaction 2 (1%) 0 0 0 0·50 --

Sun et al, 2016.

Toxicity Experience

Reduced-dose TPF induction chemotherapy improved FFS and OS for patients with stage III/IV NPCA

Induction chemotherapy reduced distant failure rates As expected, TPF induction increased grade 3/4 heme

events Majority of patients completed TPF, but only 30%

completed 3 cycles of cisplatin with radiotherapy First clinical trial to demonstrate a survival benefit for

induction vs chemoradiotherapy Results will need to be confirmed A meta-analysis of 19 trials and 4,800 patients

revealed improved OS, PFS, LRC, and DM with chemoradiotherapy ± adjuvant vs adjuvant or induction alone

PFS = progression-free survival; LRC = locoregional control. Blanchard et al, 2015.

Induction Chemotherapy for NPCA

Immunotherapy forPlatinum-Refractory HNC

Patients with platinum-refractory R/M HNSCC have a dismal prognosis, with median overall survival ≤6 months No anticancer agent improves survival for this patient

population No new treatments have been approved in >10 years

HNSCC recurrence and metastasis are facilitated by immune evasion mediated by PD-L1 and PD-L2

Both HPV-positive and HPV-negative HNSCC frequently express PD-L1

R/M = recurrent/metastatic.Herbst et al, 2015; Ferris, 2015; Badoual et al, 2013; Concha-Benavente et al, 2015.

Introduction

Sharpe et al, 2007.

Blocking PD-1/PD-L1 Restores T-Cell Function

HNSCC Cohorts of Nonrandomized, Phase Ib,

Multicohort KEYNOTE-012 Triala

aAdditional cohorts included bladder cancer, TN breast cancer, and gastric cancer. bTreatment beyond progression was allowed.cInitial cohort only. ECOG PS = Eastern Cooperative Oncology Group performance status; ORR = objective response rate.

Pembrolizumab

200 mg Q3WN=132

Continue until:• 24 months

of treatmentb

• PD• Intolerable

toxicity

Response assessment: Every 8 weeksPrimary end points: ORR (RECIST v1.1, central imaging vendor), safetySecondary end points: ORR (investigator), PFS, OS, response duration, ORR in HPV+ patientsc

Pembrolizumab

10 mg/kg Q2WN=60

Initial Cohort

Expansion Cohort

Combined

analyses of initial

and expansio

n cohorts

Patients• R/M HNSCC• Measurable

disease (RECIST v1.1)

• ECOG PS 0-1• PD-L1+

(initial cohort)• PD-L1+ or PD-

L1- (expansion cohort)

Overall Response RateKeynote 12

Data cutoff date: Apr 26, 2016. Response assessed per RECIST v1.1 (central imaging vendor review, all patients as treated)

Only confirmed responses are included

Best Overall Response

TotalN=192a

HPV+ n=45b

HPV-n=147b

n % 95% CI n % 95% CI n % 95% CI

ORR 34 18 13-24 11 24 13-40 23 16 10-23 CR 8 4 – 4 9 – 4 3 – PR 26 14 – 7 16 – 19 13 –

SD 33 17 – 7 16 – 26 18 – PD 93 48 – 19 42 – 74 50 – NAc 32 17 – 8 18 – 24 16 –

aIncludes patients who received ≥1 dose of pembrolizumab in the initial or expansion cohort.bHPV status was determined by the local institution. Cancers outside the oropharynx, identified from primary diagnosis/prior radiation/prior surgery, were considered HPV negative. cNo assessment because patient did not have central imaging review data or images were not evaluable.CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease.

Phase III CheckMate 141 Study Design

aTissue required for testing.DOR = duration of response; IV = intravenous; ORR = objective response rate; PFS = progression-free survival; Q2W = once every 2 weeks; R = randomized. Ferris et al, 2016.

Nivolumab in R/M SCCHN After Platinum Therapy

R2:1

Nivolumab 3 mg/kg IV Q2W

Investigator’s choice

• Methotrexate 40 mg/m² IV weekly

• Docetaxel 30 mg/m² IV weekly

• Cetuximab 400 mg/m² IV once, then 250 mg/m² weekly

Key eligibility criteria:

• R/M SCCHN of the oral cavity, pharynx, or larynx

• Progression on or within 6 months of last dose of platinum-based therapy

• Irrespective of no. of prior lines of therapy

• Documentation of p16 to determine HPV status (oropharyngeal)

• Regardless of PD-L1 statusa

Stratification factor:• Prior cetuximab

treatment

Primary end point:• OS

Other end points:• PFS• ORR• Safety• DOR• Biomarkers• Quality of

life

Randomized, global, phase III trial of the efficacy and safety of nivolumab vs investigator’s choice in patients with R/M SCCHN

0 3 6 9 12 15 18

Median OS, mo

(95% CI)

HR(97.73%

CI)P

Value

Nivolumab (n=240) 7.5 (5.5, 9.1) 0.70

(0.51, 0.96)

0.0101Investigator’s choice

(n=121)5.1 (4.0,

6.0)

Ferris et al, 2016.

Overall Survival: CheckMate 141

MonthsNivolumab 240 167 109 52 24 7 0

Investigator’sChoice

121 87 42 17 5 1

No at Risk

0

0

10

20

30

40

50

60

70

80

90

100

Ove

rall

Surv

ival

(%

of p

atie

nts)

1-year OS rate (95% CI)

36.0% (28.5, 43.4)

16.6% (8.6, 26.8)

Overall Survival by Tumor PD-L1 Expression at 1%

Ferris et al, 2016.


Ove

rall

Surv

ival

(% o

f pat

ient

s)

Nivolumab (n = 88)

Investigator’s Choice (n = 61)

Months0 3 6 9 12 15 18

0

10

20

30

40

50

60

70

80

90

100PD-L1 ≥1% PD-L1 <1%

HR (95% CI)0.55 (0.36,

0.83)

Ove

rall

Surv

ival

(% o

f pa

tient

s)

NivolumabInvestigator’sChoice

No. at Risk88 67 44 18 6 061 42 20 6 2 0

Nivolumab (n = 73)


Months0 3 6 9 12 15 18

0

10

20

30

40

50

60

70

80

90

100

73 52 33 17 338 29 14 6

82 0

00

HR (95% CI)0.89 (0.54,

1.45)

Overall Survival by P16 Status

Ferris et al, 2016.


Ove

rall

Surv

ival

(% o

f pat

ient

s)

Months0 3 6 9 12 15 18

0

10

20

30

40

50

60

70

80

90

100

Months0 3 6 9 12 15 18

0

10

20

30

40

50

60

70

80

90

100

Ove

rall

Surv

ival

(% o

f pat

ient

s)

Nivolumab (n = 63)


Nivolumab (n = 50)


NivolumabInvestigator’sChoice

No. at Risk63 49 35 18 10 3 0

29 20 11 4 1 0 050 32 25 12 136 26 13 7

63 1

00

HR (95% CI)0.56 (0.32,

0.99)

HR (95% CI)0.73 (0.42,

1.25)

p16-Negativep16-Positive

CheckMate 141: Treatment-Related AEs in ≥10% of Patients

AEs = adverse events.aOne grade 5 event (hypercalcemia) in the nivolumab arm and one grade 5 event (lung infection) in the investigator’s choice arm were reported. A second death occurred in the nivolumab arm subsequent to pneumonitis.Ferris et al, 2016.

Event

Nivolumab (n=236)

Investigator’s Choice (n=111)

Any Grade n (%)

Grade 3/4 n (%)

Any Grade n (%)

Grade 3/4 n (%)

Anya 139 (58.9) 31 (13.1) 86 (77.5) 39 (35.1)Fatigue 33 (14.0) 5 (2.1) 19 (17.1) 3 (2.7)Nausea 20 (8.5) 0 23 (20.7) 1 (0.9)Diarrhea 16 (6.8) 0 15 (13.5) 2 (1.8)Anemia 12 (5.1) 3 (1.3) 18 (16.2) 5 (4.5)Asthenia 10 (4.2) 1 (0.4) 16 (14.4) 2 (1.8)Mucosal inflammation 3 (1.3) 0 14 (12.6) 2 (1.8)Alopecia 0 0 14 (12.6) 3 (2.7)

Nivolumab stabilized PROs while investigator’s choice led to meaningful declines in function and worsening of symptoms

NivolumabInvestigator's choice

EORTC QLQ-C30 Physical Function

Week9 15 21

-30

-20

-10

0

10

Mea

n C

hang

e Fr

om B

asel

ine

Bet

ter

Wor

se

EORTC QLQ-C30 Social Function

9 15 21-30

-20

-10

0

10

Week

Mea

n C

hang

e Fr

om B

asel

ine

Bet

ter

Wor

se

EORTC QLQ-H&N35 Absence of Sensory Problems

9 15 21-30

-20

-10

0

10

Week

Mea

n C

hang

e Fr

om B

asel

ine

Bet

ter

Wor

se

EORTC QLQ-H&N35 Absence of Trouble With Social Contact

9 15 21-30

-20

-10

0

10

Week

Mea

n C

hang

e Fr

om B

asel

ine

Bet

ter

Wor

se

Nivolumab in R/M HNSCC After Platinum TherapyQuality of Life and Symptom Burden

PROs = patient-reported outcomes.Ferris et al, 2016

Nivolumab improved survival for patients with platinum-refractory HNC

1-year survival more than doubled compared with single-agent SOC options (docetaxel, methotrexate, or cetuximab)

All demographic and clinical subgroups appeared to benefit

The magnitude of the benefit appeared greatest for patients with PD-L1 >1% and HPV-positive tumors

SOC = standard of care.Ferris et al, 2016.

PD-1 Inhibitor Therapy for HNC

PFS was not significantly different with nivolumab vs SOC

Response rates were higher with nivolumab vs SOC

Toxicity was less with nivolumab Nivolumab stabilized QOL in comparison to

worsening QOL with SOC Pembrolizumab and nivolumab are now

FDA approved for this indication

QOL = quality of life. Ferris et al, 2016.

PD-1 Inhibitor Therapy for HNC (cont.)

Concurrent ChemoradiotherapyStandard of Care

NCCN, 2016.

Organ Preservation RegimenLarynx RT/cisplatinOropharynx RT/carboplatin/FUNasopharynx RT/cisplatin ± cis/FUUnresectable disease RT/cisplatin

RT/cetuximabPostoperative adjuvant

RT/cisplatin

Chemotherapy for Recurrent or Metastatic Head and Neck

Cancer

72-year-old presents with hoarseness and sudden onset bilateral level 2 and 3 anterior cervical adenopathy

7 pack-year smoker, nondrinker No significant comorbidities Physical exam notable for right BOT fullness and vocal

cord paralysis CT scan of the neck confirms bilateral necrotic

lymphadenopathy extending to the supraclavicular fossae

Biopsy of BOT confirms malignancy with basaloid features

PET confirms uptake in BOT, bilateral nodes, no distant metastases

Clinical stage T2N2CM0

Case Study

Which of the following options for primary therapy is not supported as a

category 1 option in the NCCN guidelines?

a. IMRT with concurrent high-dose cisplatinb. IMRT with concurrent carboplatin/5-FUc. Induction cisplatin/5-FU followed by IMRT

with concurrent carboplatind. IMRT with concurrent cetuximab

Patient receives IMRT to 72 Gy with cisplatin 100 mg/m2 x 3

PET scan at 12 weeks confirms complete response

He is well for 14 months and then develops RUQ pain

ECOG PS 1 CT scan confirms multiple liver metastases Liver biopsy confirms basaloid carcinoma Laboratory studies are notable for AST ALT 2-3 x

ULN Total bilirubin is top normal

RUQ = right upper quadrant; AST = aspartate aminotransferase; ALT = alanine aminotransferase; ULN = upper limits of normal.

Case Study

Which of the following regimens is considered the regulatory standard

and is category 1 in the NCCN guidelines for first-line

recurrent/metastatic HNC?a. Cisplatin/5-FUb. Cisplatin/paclitaxel/cetuximabc. Carboplatin/paclitaxeld. Cisplatin/5-FU/cetuximab

Patient receives 6 cycles of cisplatin/5-FU/cetuximab and has a >50% reduction in the size of his liver metastases

He is placed on maintenance cetuximab 5 months later, CT scans of the chest and

abdomen demonstrate new lung metastases and progression of liver metastases

Liver function tests and other laboratory studies are WNL

ECOG PS 1

WNL = within normal limits.

Case Study

Which of the following treatment options has been shown to improve

survival in this setting?

a. Docetaxelb. Nivolumabc. Pembrolizumabd. Cetuximabe. Axitinib

Patient receives nivolumab 3 mg/kg IV every 2 weeks for 4 cycles

He notes grade 1 fatigue, pruritus, and anorexia CT scan at 8 weeks demonstrates a partial

response to therapy After 2 more cycles of nivolumab, he presents

with low grade fever, SOB with minimal exertion, nonproductive cough, and an O2 saturation on room air of 88%

ECOG PS 2 CT scan of the chest demonstrates patchy

infiltrates

SOB = shortness of breath.

Case Study

The patient is diagnosed with grade 2 dyspnea, hypoxia and is admitted to the hospital. Which of the following is

the most likely diagnosis and recommended intervention?

a. Aspiration pneumonia, start clindamycinb. Pneumocystis carinii pneumonia, start bactrim

and steroids c. Immune-mediated pneumonitis, hold nivolumab,

rule out infection, and start prednisone 1-2 mg/kg/day

d. Pneumococcal pneumonia, start ampicillin

The patient receives high-dose steroid and symptoms resolve quickly within 48 hours. He is discharged from the hospital with a 4-week steroid taper

He arrives at the outpatient clinic without symptoms 1 week after completing steroids

Repeat CT scans confirm continued treatment response

Case Study

Which of the following therapeutic options are likely to provide the best quality of life for this patient at this

point?a. Re-initiate nivolumab now that

pneumonitis has resolved because patient had clinical benefit

b. Discontinue nivolumab and start methotrexate

c. Best supportive care and referral to hospice

d. Discontinue nivolumab, start pembrolizumab

HPV is changing the clinical landscape of HNC Be aware of new staging system specific to

HPV-positive oropharynx cancer PET surveillance after chemoradiotherapy has

similar survival to elective neck dissection with less morbidity and cost

Neck dissection improves OS and DFS in T1-T2N0 oral cavity cancer

PD1 inhibitor therapy results in clinical response and improved OS (nivolumab only) for patients with R/M platinum-refractory HNC

Key Takeaways

American Cancer Society (2016). Cancer facts & figures. Available at: http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf

Ang K, Harris J, Wheeler R, et al (2010). Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med, 363(1):24-25. DOI:10.1056/NEJMoa0912217

Badoual C, Hans S, Merillon N, et al (2013). PD-1-expressing tumor-infiltrating T cells are a favourable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res, 73(1):128-138.

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