4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ: Καρκίνος κεφαλής -...

Καρκίνος κεφαλής- τραχήλου: Εξατομικεύοντας τη θεραπεία

Αμάντα ΨυρρήΕπίκουρη Καθηγήτρια

Αττικό Νοσοκομείο

OUTLINE

• Incidence• Etiology• EGFR as a target• Studies using EGFR-targeted therapies• Checkpoint Inhibitors

Incidence

• In 2015, 45.780 new cases of oral cavity and pharynx cancer and 8.650 deaths are expected to occur in the United States

Stage Distribution by Race, United States 2004-2010

5-year Relative Survival Rates by Race and Stage , United States, 2004-2010

Etiology

• Traditionally, tobacco and alcohol use account for the majority of HNSCC

• A growing proportion of oropharyngeal squamous cell carcinomas is caused by high-risk Human Papillomaviruses (HPV), especially HPV16

Epidemic of HPV-associated OPC*

Staging and treatment overview

Early stages (I&II):30% to 40% of patients• Surgery (PLUS: no long-term radiation (RT) toxicities)• Definitive RT (PLUSES: organ preservation, patients with

comorbidities)Locally advanced non metastatic (III&IVA/B)• Definitive cisplatin chemoradiotherapy • Surgery followed by RT or cisplatin-chemoradiotherapyMetastatic disease• Palliative chemotherapy

Mountzios G, T Rampias and A.Psyrri. Ann Oncol 2014;25:1889-1900

EGFR as a molecular target in HNSCC

• EGFR expression linked to poorer outcome1 and reduced response to radiotherapy2,3

1. Psyrri, et al. Clin Can Res 2005;11:5856-622. Baumann M, Krause M. Radiother Oncol 2004;72:257‒266

3. Ang KK, et al. Cancer Res 2002;62:7350–7356

Cetuximab• Cetuximab

– IgG1 mAb– Chimeric protein– Specifically binds with

high affinity to FcγRI (EC50 = 0.13 nM) and FcγRIIIa (EC50 = 6 nM)

– Induces apoptosis and ADCC*

– Preclinical synergistic activity in combination with chemotherapy and radiotherapy

*ADCC: antibody dependent cellular cytotoxicity

Cancer Cell Volume 7, Issue 4 2005 301 - 311

EGFR, epidermal growth factor receptor; mAb

Strategies to improve outcomes in HNSCC utilizing EGFR inhibitors

• Treatment intensification of locally advanced HNSCC to improve OS

- Randomized trials: CRT+EGFR inhibitor versus CRT• EGFR inhibition in the post-induction setting to

reduce toxicity in sequential design- Randomized phase II studies of induction

chemotherapy followed by either chemoradiotherapy or cetuximab radiotherapy to reduce toxicity without compromising efficacy

CRT: chemoradiotherapy; OS: overall survival

Randomized trials of EGFR inhibitor plus chemoradiation in HNSCC

AUTHOR # pts Treatment Comparator Primary Endpoint Setting S vs E P

value

Giralt et al 2012 150 C+EBRT+P C+ EBRT 2 yr LRC Locally

advanced

68% vs

61%0.3

Martins et al2013 204 C+RT+

ErlotinibC+RT CRR Locally

advanced

40% vs

52%0.08

Ang et al2011 895 C+RT+

cetuximab C+RT PFS Locallyadvanced

64%vs

63%NS

C: cisplatin; EBRT: external beam radiation therapy; RT: radiation therapy; S: standard, E: experimental arm; P: Panitumumab; CRR: complete response rate

EGFR inhibitor + Chemoradiation: Toxicity

TOXICITY GRADE > 3 Author Mucositis Skin

ReactionsSkin

Reactions out of Field

E S E S E S

Ang 43% 33% 25% 15% 29% 1%Giralt 11% 5% 28% 13% 11% 0%Martins 48% 48% 13% 2% NR NR

Strategies to improve outcomes in HNSCC utilizing EGFR inhibitors

• Treatment intensification of locally advanced HNSCC to improve OS

-Randomized trials: CRT+EGFR inhibitor versus CRT• EGFR inhibition in the post-induction setting to

reduce toxicity in sequential design-Randomized phase II studies of induction chemotherapy followed by either chemoradiotherapy or cetuximab radiotherapy to reduce toxicity without compromising efficacy

CRT: chemoradiotherapy; OS: overall survival

The Randomized Phase II Study: TREMPLIN

P: cisplatin; F: 5-fluorouracil; T: docetaxel; TL: total laryngectomy; PR: partial response ; RT: radiotherapy; CT: computed tomography; Tx: treatment

TPF (153 patients)3 cycles, 1 cycle q3w

T = 75 mg/m² on day 1P = 75 mg/m² on day 1

F = 750 mg/m² on day 1 to 5

60 patients: RT 70 Gy Cisplatin 100 mg/m² on days 1, 22 and 43

56 patients: RT 70 GyERBITUX 400 mg/m² 1 wk prior to RT then 250 mg/m² weekly on wks 1 to 7

R

Total laryngectomy + post-op RT

< PR 23

≥ PR116

•Previously untreated SCC larynx/hypopharynx suitable for TL•Primary Endpoint: larynx preservation 3 months after treatment•Secondary Endpoints: larynx function preservation and survival•18 months after treatment

Lefebvre et al: JCO 2013Mar;31(7):853-9

Acute toxicity during RT

Cisplatinn = 58

ERBITUXn = 56

p-value

Grade 3 mucositisGrade 4 mucositis

25 (43%)2

24 (43%)1 NS

Grade 3 in field skin toxicityGrade 4 in field skin toxicity

14 (24%)1

29 (52%)3

< 0.001

Other toxicities, any grade, justifying a protocol modification Renal toxicity Hematological toxicity Poor general condition Infusion-related reaction

9 (15.5%)8 (14.0%)7 (12.0%)

0

00

1 (1.7%)3 (5.0%)

Protocol modification due to acute toxicity 33 (57%) 19 (29%) 0.02

* 2 patients did not start the treatment in the cisplatin arm


Carcinologic events (ITT)

At 18 months after endof treatment

Last evaluation with a median follow-up of 36 months

Cisplatin ERBITUX p-value Cisplatin ERBITUX p-value

Total of local (+/- regional) failures 5 (8.3%) 8 (14.3%) Log-rank:

0.307 (11.7%) 12 (21.4%) Log-rank:

0.14

Feasible salvage total laryngectomy 0/4* 7/8 0.01 1/6* 9/12

(1 refused) 0.04

Successful salvage total laryngectomy 0/1 7/8

Ultimate local failure rate 6 (10%)* 5 (8.9%) NS

Regional failure alone 5 (8.3%) 5 (8.9%) NS 5 (8.3%) 5 (8.9%) NS

Distant metastases 2 (3.3%) 2 (3.6%) NS

Second primary tumor 3 (5.0%) 3 (5.3%) NS

* Data missing for 1 patient lost to follow-up at 5 months

ITT: intention to treat


Endpoints (ITT)

Primary endpoint (3 months after end of Tx)

Cisplatin n = 60

ERBITUXn = 56

p-value

Larynx preservation, n (%)(larynx in place without tumor)

57 (95%) 52 (93%) 0.63

Secondary endpoints (18 months after end of Tx)

Cisplatin n = 60

ERBITUXn = 56

p-value

Larynx function preservation, n (%)(larynx in place without tumor/trach/feeding tube)NB: at 18 months or at death

52 (87%) 46 (82%) 0.68

Overall survivalNB: since randomization 92 % 89 % Log-rank: 0.44

NB: 1 pt lost to FU in the Cisplatin arm is considered as failure

OS by HPV status in prospectiveclinical trials

Regimen Time HPV + vs HPV - P value

Induction+CRT(ECOG)

2 year 95% vs 62% 0.005

CRT (TROG2.2) 2year 94% vs 77% 0.007

CRT (RTOG0129) 3 year 79%vs 46% 0.002

Induction+CRT (TAX324)Radiation (DAHANCA) 5year

5year

93% vs 35%

62% vs 26%

<0.001

0.003

Rationale for treatment de-intensification

• The better outcome of HPV+ HNSCC raises the question as to whether we can reduce the intensity of treatment in this patient population

• These patients are young and should not suffer the consequences of unnecessary overtreatment

LRC (months)

Results: LRC of RT + cetuximab compared with RT alone in p16-positive OPC

No. risk OPC p16 positive (n=75)RT 34 24 20 12 6 0RT + cet 41 33 30 21 12 0

0.00.10.20.30.40.50.60.70.80.91.0

Prob

abili

ty o

f LR

C

0 12 24 36 48 60

RT + cet; p16 +

RT; p16 +

87%

65% HR=0.31 [0.11–0.88]

Rosenthal D et al: ICHNO 2015

Presented by: Anthony J. Cmelak, MD

Cisplatin 75/m2 d1Paclitaxel 90/m2 d1,8,15Cetuximab 250/m2 d1,8,15

Q 21 days for 3 cycles

ER VE AS LP UO AN TS I E O

N

CLINICAL CR Low dose IMRT 54Gy/27fx* + Cetuximab qWeek

CLINICAL PR/SDFull dose IMRT 69.3Gy/33fx* + Cetuximab qWeek

Induction Chemotherapy

Concurrent Chemoradiation

IMRT margins for primary: 1.0 to 1.5cm around gross dz Nodal margin: 1cm margin minimum, treat entire nodal level

Eligibility•OPSCC•resectable•HPV ISH + and / or p16+•Stage III,IVA

ECOG 1308: Phase II Schema

Response: Induction


Clinical Response Primary Site NodesCR 75 (71%)* 48 (61%)

PR 7 (9%) 19 (24%)

SD 11 (14%) 7 (9%)

Unevaluable 5 (6%) 5 (6%)

Radiographic Response Primary Site Nodes

CR 38 (48%) 4 (5%)

PR 24 (30%) 55 (70%)

SD 9 (11%) 17 (22%)


* 6 patients had biopsies performed on primary after baseline scans

Response: Following Cetux/IMRT


Clinical Response Primary Site NodesCR/PR 75 (94%) 74 (94%)

SD 0 (0%) 19 (24%)


Radiographic Response Primary Site Nodes

CR/PR 65 (81%) 74 (94%)

SD 5 (6%) 3 (4%)


Endpoint: 2yr PFS and OS


Cohort (n) 2 year PFS (90% CI) 2 year OS (90% CI)All low dose pts (62) 0.80 (0.70, 0.88) 0.93 (0.85, 0.97)

T4a (7) 0.54 (0.19, 0.79) 0.86 (0.45, 0.97)

Non-T4a (55) 0.84 (0.73, 0.91) 0.94 (0.86, 0.98)

N2c (19) 0.77 (0.56, 0.89) 0.95 (0.76, 0.99)

Non-N2c (43) 0.82 (0.69, 0.90) 0.93 (0.82, 0.97)

Smoker >10pk-yrs (22) 0.57 (0.35, 0.73) 0.86 (0.67, 0.94)

Smoker ≤10pk-yrs (40) 0.92 (0.81, 0.97) 0.97 (0.87, 0.995)

Smoker ≤10k-yrs, <T4, N2c (27)

0.96 (0.82, 0.99) 0.96 (0.82, 0.99)

All high-dose pts (15)* 0.65 (0.41, 0.82) 0.87 (0.63. 0.96)

* 3 high-dose pts did not go on to receive RT

PFS and Survival: Dose


2-yr = 80%

2-yr = 65%

2-yr = 87%

2-yr = 93%

Best Outcome: <T4, T1-N2b, <10 pk-yr


2-yr = 96%

2-yr = 64%

Radiation Therapy Oncology Group 1016 : Study Design

• Stage III/IV • Oropharynx• P16+

RANDOMIZE

II: Accelerated IMRT 70Gy/6weeks (cetuximabx8)

I: accelerated IMRT 70Gy/6weeks(cisplatin 100 mg/m², d1, 22)

Stratification factors: , cN-stage (cN0-2a vs cN2b- cN3), cT-stage (T1-2 vsT3-4) Zuprod Performance Status (0 vs 1), smoking history (<10py vs >10py)

Presented by: Amanda Psyrri

Recurrent/Metastatic HNSCC: Cytotoxic Agents

First-line therapy• For fit patients: first-line option should include the combination of

cetuximab with cisplatin or carboplatin plus 5-Fluorouracil (PF)4,5 (category 1) or platinum-taxane combinations+/- cetuximab or cisplatin plus 5-Fluorouracil or cetuximab

• For patients with poor PS: use single agent chemotherapy or cetuximab4

Second-line therapy• For fit patients: chemotherapy, cetuximab, clinical trial or best

supportive care5-median overall survival 3-6 months 4. Gregoire V et al: Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice

Guidelines for diagnosis, treatment and follow-up Ann Oncol 2010 5. NCCN guidelines v2.2014

32. NCCN. Clinical practice guidelines in oncology: head and neck cancers. v.2.2013.

EXTREME: Phase III Study Design

cetuximabuntil PD

R/M SCCHN• Prior CT• KPS (<80 vs. ≥80) CT + cetuximab

Primary endpoint: OS Secondary endpoints: PFS, RR, safety

CT Cisplatin (100 mg/m2 IV, day 1) orCarboplatin (AUC 5, day 1) + 5-FU (1000 mg/m2 IV, days 1–4)Every 3 weeks, up to 6 cycles

cetuximabInitial dose 400 mg/m2

then 250 mg/m2 weeklyuntil PD

n=442

CT

Vermorken et al. N Engl J Med 2008CT, chemotherapy; KPS, Karnofsky performance status; OS, overall survival; PD, progressive disease; PFS, progression free survival; RR, response rate

127153

83118

6582

4757

1930

173184

220222

815

13

HR : 0.80 (95% CI: 0.64-0.99; P = .04)

Chemotherapy only (n = 220) 20Chemo + cetuximab (n = 222) 36

Surv

ival

Pro

babi

lity

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 3 6 9 12 15 18 21 24

10.1 mos7.4 mos

Pts at Risk, nCTX only

CET + CTX

Survival Time (Mos)

Cetuximab ± First-line Platinum in Recurrent or Metastatic HNSCC: OS

ORR, %

37. Vermorken JB, et al. N Engl J Med. 2008;350:1116-1127.

Cetuximab ± First-line Platinum in Recurrent or Metastatic HNSCC:

Safety

38. Vermorken JB, et al. N Engl J Med. 2008;350:1116-1127.

Grade 3/4 AEs in ≥ 5% of Pts, n (%)

Cetuximab +Chemotherapy

(n = 219)

Chemotherapy Alone (n = 215) P Value*

Grade 3/4 Grade 4 Grade 3/4 Grade 4

Any event 179 (82) 67 (31) 164 (76) 66 (31) .19

Neutropenia 49 (22) 9 (4) 50 (23) 18 (8) .91

Anemia 29 (13) 2 (1) 41 (19) 2 (1) .12

Thrombocytopenia 24 (11) 0 24 (11) 3 (1) 1.00

Leukopenia 19 (9) 4 (2) 19 (9) 5 (2) 1.00

Skin reactions 20 (9) 0 1 (< 1) 0 < .001

Hypokalemia 16 (7) 2 (1) 10 (5) 1 (< 1) .31

Cardiac events 16 (7) 11 (5) 9 (4) 7 (3) .22

Vomiting 12 (5) 0 6 (3) 0 .23

Asthenia 11 (5) 1 (< 1) 12 (6) 1 (< 1) .83

Anorexia 11 (5) 2 (1) 3 (1) 1 (< 1) .05

Hypomagnesemia 11 (5) 8 (4) 3 (1) 1 (< 1) .05

Febrile neutropenia 10 (5) 2 (1) 10 (5) 4 (2) 1.00

*Comparing Grade 3 and 4 combined.

Impact of Human Papillomavirus (HPV) and p16 Status on Survival and Response with Cisplatin plus 5-FU and Cetuximab in

Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

(R/M SCCHN): Analysis of the Phase III EXTREME Trial

A. Psyrri, R. Mesía, F. Peyrade, F. Beier, B. de Blas, I. Celik,

L. Licitra, Jan B Vermorken ESMO 2012

Overall Survival: Interaction-HPV Status and Treatment

Number of subjects at riskGroup 1 :Group 2 :Group 3 :Group 4 :

11145 13152

10123 8119

8101 8 83

7 75 4 52

6 52 4 40

4 34 3 29

2 18 2 12

0 10 1 5

0 2 1 0

0 0 0 0

'

'

'

'

'

Group 1: Cetuximab + CTX Positive Results Censored Event Group 2: Cetuximab + CTX Negative Results Censored event

Group 3: CTX Positive Results Censored Event Group 4: CTX Negative Results Censored event

Sur

viva

l Dis

tribu

tion

Func

tion

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Survival Time (months)

0 3 6 9 12 15 18 21 24 27

Protocol: EMR 62 202 - 002 - Clinical data cut-off: 12MAR2007- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Figure 1.3.2.1: Overall Survival - Interaction ITT Population (HPV Evaluable Subjects)

Note: Analysis performed based on the 28MAR2007 data snapshot.

George

This figure is going to be redrawn and will be comparable to the one on slide 14

Overall Survival by HPV StatusHPV+ patients HPV- patients

HR (95% CI) 0.63 (0.30–1.34)p-value 0.22

HR (95% CI) 0.82 (0.65–1.04)p-value 0.11

Number of subjects at riskGroup 1 :Group 2 :

11 13

10 8

8 8

7 4

6 4

4 3

2 2

0 1

0 1

0 0

'

'

'

''

Group 1: Cetuximab + CTX Censored Event

Group 2: CTX Censored event

Sur

viva

l Dis

tribu

tion

Func

tion

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0


0 3 6 9 12 15 18 21 24 27


Figure 1.1.2.2: Overall Survival by Treatment Group ITT Population (HPV Positive Subjects)


Number of subjects at riskGroup 1 :Group 2 :

145152

123119

101 83

75 52

52 40

34 29

18 12

10 5

2 0

0 0

'

'

'

'

'

Group 1: Cetuximab + CTX Censored Event Group 2: CTX Censored event

Sur

viva

l Dis

tribu

tion

Func

tion

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0


0 3 6 9 12 15 18 21 24 27


Figure 1.1.2.3: Overall Survival by Treatment Group ITT Population (HPV Negative Subjects)


George

This figure is going to be redrawn and will be comparable to the one on slide 16

Afatinib versus methotrexate as second-line treatment for patients with R/M HNSCC who

progressed after platinum-based therapy: primary efficacy results of

LUX-Head & Neck 1, a Phase III trial

J-P. H. Machiels, R. I. Haddad, J. Fayette, L. F. Licitra, M. Tahara, J. B. Vermorken, P. M. Clement, T. Gauler, D. Cupissol, J. J. Grau, J. Guigay, F. Caponigro, G. de Castro Jr, L. de Souza Viana, U. Keilholz, J. M. del Campo, X. Cong,L.Svensson,E.Ehrnrooth, and E. E. W. Cohen on behalf of the LUX-H&N 1 investigators

• Afatinib is an irreversible ErbB-family blocker1–3

– Inhibits all kinase-active members: EGFR, HER2 and HER4

– Approved* in the major ICH regions of US, EU and Japan for the treatment of patients with NSCLC harbouring distinct types of EGFR-activating mutations

HER2, human epidermal growth factor receptor-2; HER4, human epidermal growth factor receptor-4; ICH, International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use *Indications differ between countries

1. Li D, et al. Oncogene 2008;27:4702–11; 2. Solca F, et al. J Pharmacol Exp Ther 2012;343:342–50; 3. Yarden Y, Pines G. Nat Rev Cancer. 2012;12:553–563;

Afatinib: irreversible ErbB-family inhibitor

PROLIFERATION SURVIVAL

RAS

ERK

AKT

RAF

MEK

P13K

mTOR

EGFR/HER2

HER2/ErbB3

ErbB4/ErbB3

AfatinibGefitinibErlotinib

Afatinib

Primary endpoint: PFS independent review

CI, confidence interval; MTX, methotrexate

Time (months)

0

0.2

0.4

0.6

0.8

1.0

0 3 6 9 12

Estim

ated

PFS

pro

babi

lity

15 18

No. of patientsAfatinib 322 93 26 9 3 1 0MTX 161 28 6 2 0 0 0

Afatinib(n=322)

MTX(n=161)

PFS event, n (%) 275 (85.4) 135 (83.9)Median PFS (months) 2.6 1.7HR (95% CI) 0.80 (0.65–0.98)Log-rank test p-value 0.030

42.8%

30.5%

+ 0.9 months

Overall survival – LUX-1

Time (months)

Estim

ated

OS

prob

abili

ty

No. of patientsAfatinib 322 255 172 89 53 28 14 6 1 0MTX 161 115 76 48 29 16 9 7 3 0

Afatinib(n=322)

MTX(n=161)

OS event, n (%) 237 (73.6) 121 (75.2)Median OS (months) 6.8 6.0HR (95% CI) 0.96 (0.77–1.19)Log-rank test p-value 0.700

0

0.2

0.4

0.6

0.8

1.0

0 3 9 15 21 24 2718126

+ 0.8 months

PD-1/PD-L1 in Immune Response Blockade

26-30 September 2014, Madrid, Spain esmo.org

Antitumor Activity of the anti-PD-1 Antibody Pembrolizumab in biomarker-unselected Patients with

R/M Head and Neck Cancer: Preliminary Results from the KEYNOTE-012 Expansion Cohort

Tanguy Seiwert,1 Robert Haddad,2 Shilpa Gupta,3 Ranee Mehra,4 Makoto Tahara,5 Raanan Berger,6 Se-Hoon Lee,7 Barbara Burtness,4 Dung Le,8 Karl Heath,9 Amy Blum,9 Marisa

Dolled-Filhart,9 Kenneth Emancipator,9 Kumudu Pathiraja,9 Jonathan D. Cheng,9 Laura Q Chow10

1Department of Medicine, The University of Chicago, Chicago, IL, USA; 2Dana Farber Cancer Institute, Boston, MA, USA; 3H.Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 4Fox Chase Cancer Center, Philadelphia, PA, USA; 5National Cancer Center Hospital East, Kashiwa, Japan; 6Sheba Medical Center, Tel Hashomer, Israel, 7Seoul National University

Hospital, Seoul, Korea; 8Johns Hopkins University, Baltimore, MD, USA; 9Merck & Co., Inc. Kenilworth, NJ, USA, 10University of Washington, Seattle, WA, USA.

Presented by:

Tanguy Seiwert, MDAssistant Professor of Medicine

Associate Director Head and Neck Cancer ProgramFellow, Institute of Genomics and Systems Biology

The University of Chicago

42

HNSCC expansion cohort of the KEYNOTE-012 Nonrandomized, Phase 1b Multi-cohort trial*

*Additional cohorts included bladder cancer, TN breast cancer, and gastric cance †Treatment beyond progression was allowed. ‡Re-treatment was permitted.

Patients: • Recurrent or metastatic

HNSCC, regardless of PD-L1 or HPV status

• Have measurable disease based on RECIST 1.1

• ECOG performance status of 0 or 1

Pembrolizumab 200 mg Q3W

• Treatment for 24 months†

• Documented disease progression‡

• Intolerable toxicity

Response assessment: Every 8 weeks

Primary end points: ORR per modified RECIST v1.1 by investigator review; safety

Secondary end points: PFS, OS, duration of response

43

Baseline DemographicsCharacteristic N = 132*

N (%)

Median age (range), years 60 (25−84)

Male 110 (83.3)

Race

White 96 (72.7)

Asian 28 (21.2)

Other 8 (6.1)

ECOG PS

[0] Normal Activity

38 (28.8)

[1] Symptoms, but ambulatory

94 (71.2)

Characteristic N = 132*N (%)

Prior adjuvant/neoadjuvant systemic therapy

Yes 53 (40.2)

Prior lines of therapy for recurrent/metastatic disease

0 22 (16.7)

1 30 (22.7)

2 28 (21.2)

3 or more 50 (37.9)

Unknown 2 (1.5)

Data cutoff date: March 23, 2015*Includes patients who received ≥1 dose of pembrolizumab

44

Treatment-Related Adverse EventsGrades 3-5 (≥2 patients)

N = 132* N (%)

Any 13 (9.8)Swelling face 2 (1.5)Pneumonitis 2 (1.5)

AE in ≥5 % of Patients N = 132*N (%)

Any 79 (59.8)

Fatigue 20 (15.2)

Hypothyroidism 12 (9.1)

Decreased appetite 10 (7.6)

Rash 10 (7.6)

Dry skin 9 (6.8)

Pyrexia 9 (6.8)

Arthralgia 7 (5.3)

Nausea 7 (5.3)

Weight decreased 7 (5.3)

*Includes patients who received ≥1 dose of pembrolizumabData cut off date: March 23, 2015.

• No treatment-related deaths occurred

45

Overall Response Rate [Site Radiology Review]*

Best overall responseTotal

N = 117†

HPV+ n = 34

HPV−n = 81

n (%) 95% CI n (%) 95% CI n (%) 95% CI

ORR 29 (24.8) 17.3-33.6 7 (20.6) 8.7-37.9 22 (27.2) 17.9-38.2

Complete Response 1 (0.9) 0.0-4.7 1 (2.9) 0.1-15.3 0 (0) 0-4.5

Partial Response 28 (23.9) 16.5-32.7 6 (17.6) 6.8-34.5 22 (27.2) 17.9-38.2

Stable Disease 29 (24.8) 17.3-33.6 9 (26.5) 12.9-44.4 19 (23.5) 14.8-34.2

Progressive Disease 48 (41.0) 32.0-50.5 13 (38.2) 22.2-56.4 34 (42.0) 31.1-53.5

No Assessment# 9 (7.7) 3.6-14.1 4 (11.8) 3.3-27.5 5 (6.2) 2.0-13.8

Non-evaluable± 2 (1.7) 0.2-6.0 1 (2.9) 0.1-15.3 1 (1.2) 0.0-6.7

*Unconfirmed and confirmed RECIST v 1.1 responses†Includes patients who received ≥1 dose of pembrolizumab, had measurable disease at baseline and ≥1 postbaseline scan or discontinued due to PD or DRAE. 15 patients not included in this analysis: 2 did not

have baseline scans within screening window, 13 did not have post-baseline assessment and discontinued due to non-drug related AE (7), subject withdrawal of consent (4), other (2).#No assessment: Discontinued without post-baseline radiographic assessment due to drug related AE (2 patients), clinical PD (6 patients), death due to PD (1 patient)±Non-evaluable: Images were not of sufficient quality to be evaluableHPV status missing for 2 patients with oropharynx cancer. Cancers outside the oropharynx are considered HPV negative by convention.Data cutoff date: March 23, 2015.

Overall Survival Data Head & Neck Cancer Program

Durvalumab (MEDI4736) Efficacy in HNC:

Presented by: Matt Fury, ESMO 2014

Durvalumab/MEDI4736: Clinical Data – ASCO 2015

48ASCO 2015: Advances in Head

and Neck CancerSegal et al. ASCO 2015

Durvalumab/MEDI4736: Clinical Data – ASCO 2015

49ASCO 2015: Advances in Head and Neck CancerSegal et al. ASCO 2015

HPV(-) patients seemed to have improved responses over HPV(+) patients

Durvalumab was safe and tolerable– Drug-related AEs: 60% – Grade ≥3 drug-related AEs: 7%

Pis: Tanguy Seiwert and Amanda Psyrri

ConclusionsConclusions

• Cetuximab remains the only targeted therapy approved in HNSCC

• Until the results of RTOG1016 become available, cisplatin- containing

chemoradiotherapy remains the standard of care for HPV+ locally

advanced oropharyngeal cancer

• Immune checkpoint inhibitors hold promise in HNSCC

4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ: Καρκίνος κεφαλής -...

Health & Medicine

Transcript of 4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ: Καρκίνος κεφαλής -...