ESMO SUMMIT LATIN AMERICA 2019

Head and Neck Cancer in Latin America

Dr. Nora Sobrevilla Moreno

Medical OncologistHead and Neck, Melanoma an GU cancers

Insituto Nacional de Cancerología, México City, Mexico

CONFLICT OF INTEREST DISCLOSURESub-title

Advisory board:BMS, MSD, Pfizer, Eisai, Ipsen, Bayer.

Speaker:BMS, MSD, Pfizer, Eisai, Ipsen, Bayer.

Research:BMS, MSD, Pfizer.

HEAD AND NECK CANCER IS A HETEROGENOUS DISEASE

90% of head and neck cancers have squamous-cell histology (HNSCC).

Other sites:• Paranasal sinuses• Salivary glands

Nasal antrum

Nasopharynx

OropharynxBase of tongueSoft palateTonsillar pillarand fossa

Hypopharynx

Esophagus

SupraglottisFalse cordsArytenoidsEpiglottisArytenoepiglottic foldGlottisSubglottis

LipBuccal mucosaAlveolar ridge and retromolar trigoneFloor of mouthHard palateOral tongue (anterior two thirds)

Oral cavity

Larynx

Pharynx

EPIDEMIOLOGY

Head and neck cancer respresent the seventh more common cause of cancer in the world. Approximately 705,781 new cases in the world.

https://gco.iarc.fr/today/home

Head and neck cancer respresent the eighth more common cause of cancer deaths in the world. Approximately 358,144 deaths in the world.

EPIDEMIOLOGY OF HNSCCWorld

Eighth cause of cancer in Latin America

Seventh cause of cancer deaths in Latin America

https://gco.iarc.fr/today/home

EPIDEMIOLOGY OF HNSCCWorld

EPIDEMIOLOGY OF HNSCCLatin America

Cancers ranked by age-standardized incidence rates among males in Central and South America

Sierra MS., et al. Cancer Epidemiol (2016);44S:S23-S42

Cancers ranked by age-standardized mortality rates among males in Central and South America

Sierra MS., et al. Cancer Epidemiol (2016);44S:S23-S42

Males have higher incidence thanwomen, with the lower male:femaleratios presenting in El Salvador, Peruand Guatemala (other: Mexico,Ecuador, Bolivia, Haiti).

Males have higher mortality ratesthan females, with the lowermale:female ratio in Peru andEcuador (other Guatemala, Boliviaand El Salvador).

MALE:FEMALE RATIO OF HNSCCLatin America

RISK FACTORS

RISK FACTORS FOR HEAD AND NECK CANCER

• Age: (patients older 60 years old).• Sex: Men

• Tobacco.• Alcohol.• Other oral substances: Betel nut.

• Virus HPV EBV

Chaturvedi AK, et al. J Clin Oncol. 2011;29:4294-4301.

ALCOHOL AN TOBACCO CONSUMPTION ARE RISK FACTORS FOR H&N CANCER

Hashibe M., et al. J Natl Cancer Inst 2007;99:777-89

At least 75% of H&N cancers areattributable to tobacco and alcoholdrinking.

PREVALENCE OF TOBACCO SMOKING IN LATIN AMERICA

CURRENT SMOKING PATTERNS IN LATIN AMERICA

Pineros M., et al. Cancer Epidemiol 2016;44S:S90-S99

PREVALENCE OF ALCOHOL CONSUMPTION STATUS IN THE WORLD

Global status report on alcohol and health 2018. Geneva: World Health Organization; 2018.

PORPORTION OF UNRECORDED TOTAL ALCOHOL PER CAPITA CONSUMPTION (APC) AMONG CURRENT DRINKERSWHO regions

Global status report on alcohol and health 2018. Geneva: World Health Organization; 2018.

TRENDS OF ALCOHOL CONSUMPTION IN THE WORLD

Global status report on alcohol and health 2018. Geneva: World Health Organization; 2018.

VIRAL INFECTION AND CANCER

https://gco.iarc.fr/causes/infections/home

HPV IS ASSOCIATED WITH PROGNOSIS IN OP SCC

Low risk: HPV+ with ≤ 10 pk-yrs or > 10 pk-yrs and N0-N2a cancerIntermediate risk: HPV+ with > 10 pk-yrs or HPV‒ with ≤ 10 pk-yrsand T2-T3 cancerHigh risk: HPV‒ with ≤ 10 pk-yrs and T4 cancer or > 10 pk-yrs

93.0%

70.8%

46.2%

Ang KK, et al. N Engl J Med. 2010;363:24-35

AJCC 8TH EDITION: OROPHARYNX

Lydiatt WM., et al. CA Cancer J Clin 2017;67:122-137

HPV PREVALENCE IN HNSCC

Ndiaye C., et al. Lancet Oncol 2014;15:1319-31

HPV PREVALENCE IN HNSCC

p16/HPV16 positivity in OP varied according to region:

- Brazil: 4.1%- Europe: 31%- US: 59%

p < 0.001

D´Souza G., et al. Oral Oncol 2016;62:20-17

HPV PREVALENCE IN HNSCC

• 1090 cases of OP cancer over the world.

• 819 HPV-DNA negative.• 271 HPV-DNA positive.• 158 cases of OP cancer from Central

and South America

• Argentina, Bolivia, Chile, Colombia, Ecuador, Paraguay, Venezuela.

• Guatemala, Honduras, México.

Castellsagué X., et al. J Natl Cancer Inst 2016;108:djv403

DIAGNOSIS

https://gco.iarc.fr/tomorrow/home

TIME TRENDS FOR HNSCCWorld

LarynxLip, Oral cavity & Pharynx

INCIDENCE AND MORTALITY TIME TRENDSLatin America: 1985-2010

Perdomo S., et al. Cancer Epidemiology 2016;44S:S43-S52

Incidence Mortality

Lip, Oral Cavity

Larynx

Oropharynx

Hypopharynx

HEAD AND NECK INCIDENCE AND MORTALITY BURDEN: TIME TRENDS.

https://gco.iarc.fr/tomorrow/home

31%47%

18% 5%

Stage Distribution at Diagnosis*[1]

LocalizedRegionalDistantUnknown

83%61%

37% 49%

0.0%

100.0%

5-Year Relative Survival*[1]

56%

21%

19% 5%

Stage Distribution at Diagnosis*[1]

LocalizedRegionalDistantUnknown

75%

43% 35%56%

0.0%

100.0%

5-Year Relative Survival*[1]

1. National Cancer Institute. SEER Stat Fact Sheets: Oral Cavity and Pharynx Cancer. Available at: http://seer.cancer.gov/statfacts/ html/oralcav.html. Accessed September 15, 2014. 2. National Cancer Institute. SEER Stat Fact Sheets: Larynx Cancer. Available at: http://seer.cancer.gov/statfacts/html/laryn.html. Accessed September 15, 2014

Oral Cavity and Pharynx

Larynx

STAGE DISTRIBUTION AND SURVIVAL OF OC, PHARYNX AND LARYNX CANCER IN THE USA.

DISTRIBUTION OF CLINICAL STAGES IN HNSCCBrazil

D´Souza G., et al. Oral Oncol 2016;62:20-17

• Significant morbidity and mortality.• Survival advantage of early diagnosis.• Association of identifiable risk factors.• Ability to diagnose early stage tumors with a clinical

examination.

SCREENING FOR HNSCCWhy does it makes sense?

Three rounds of oral visual examination at three-year intervals.

PPV 74%. Sensitivity: 64%. Absolute reduction in oral cancer mortality non significant. Reduction of mortality in tobacco and alcohol users: 34% Conclusion: Oral visual screening has the potential to prevent 37000 deaths from oral cancer every year among

smokers and drinkers.

SCREENING EXPERIENCE IN HNSCCIndia

Gogarty DS. J Laryngol Otol 2016;130:8-14

National screening program for head and neck cancer malignancies. All citizens 15 years and above. Annual oral visual inspection by dentists.

Data collected between 1984-1990. Reference of 6091 patients (35% complied with referral).

Stage I diagnosis increased from 22.8% to 48.2% Stage II-IV cases decreased from 77.2 to 51.8%

SCREENING IN HNSCC Cuba experience

Gogarty DS. J Laryngol Otol 2016;130:8-14

TREATMENT

Developed countries: approximately 50%. Developing countries: >55%, may reach

70–80% of patients in some areas. Actual RTU developing countries: 25%-

40%. A radiotherapy machine is required for

every 400–600 new radiotherapy patientsper year.

High income countries 1:120 000 patients. Middle income countries 1: 1 million

patients. Low income countries 1: 5 million patients.

RADIOTHERAPY UTILIZATION RATES (RTU)

Rossenblatt E., et al. Radiotherapy in cancer care: facing the global challenge / International Atomic Energy Agency 2017.

RADIOTHERAPY NEEDS AND TYPE OF COVERAGE

Camacho-Rodríguez R., et al. Radiotherapy in cancer care: facing the global challenge / International Atomic Energy Agency 2017.

Chemoradiotherapy:

Organ preservation. Definitive. Adjuvant.

Induction chemotherapy.

CHEMOTHERAPY IS A STANDARD OF CARE FOR LOCALLY ADVANCED HEAD AND NECK CANCERS

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)

ORR, %

Vermorken JB, et al. N Engl J Med. 2008;350:1116-1127. Ferris RL., et al. N Engl J Med 2016;375:1856

APPROVED TREATMENTS BEYOND CHEMOTHERAPY FOR HEAD AND NECK CANCERS

APPROVAL AND ACCESS OF CETUXIMAB AND NIVOLUMAB IN LATIN AMERICA

Country Cetuximab NivolumabLA HNSCC Recurrent/metastatic R/M Platinum resistant

Argentina Fully reimbursed Fully reimbursed Fully reimbursed

Brazil Not reimbursed Not reimbursed Not approved

Chile Partially reimbursed Partially reimbursed Partially reimbursed

Costa Rica Not reimbursed Fully reimbursed Not approved

Colombia NA NA Partially reimbursed

Dominican Republic Fully reimbursed Fully reimbursed Not approved

Ecuador Fully reimbursed Partially reimbursed Not approved

El Salvador Fully reimbursed Fully reimbursed Not approved

Guatemala Fully reimbursed Fully reimbursed Not approved

Honduras Fully reimbursed Fully reimbursed Not approved

Mexico Partially reimbursed Partially reimbursed Partially reimbursed

Nicaragua Fully reimbursed Fully reimbursed Not approved

Panama Fully reimbursed Fully reimbursed Not approved

Peru Fully reimbursed Not reimbursed Partially reimbursed

Venezuela Fully reimbursed Fully reimbursed Not approved

Data provided by Merck Mexico and BMS Mexico

ECONOMIC BURDEN OF NEWER THERAPIES IN HEAD AND NECK CANCER

Banford J., et al. Nat Rev Drug Disc 2017;16:235-36

REGISTERED CLINICAL TRIALS IN HEAD AND NECK CANCER IN LATIN AMERICA

Number of clinical studies

Completed/Terminated

Active, not recruiting

Recruiting Investigator Initiated

Pharma initiative

Argentina 14 9 3 2 1 13Brazil 33 19 7 7 19 14Chile 8 5 2 1 3 5Colombia 3 1 0 2 0 3Cuba 3 1 0 2 2 1Mexico 11 5 4 2 1 10Peru 4 4 0 1 3Uruguay 2 1 0 1 1 1

United States 1233 registered studies.Canada 171 registered studies.

https://clinicaltrials.gov/

PERSPECTIVES FOR HNSCC IN LATIN AMERICA

Decreasing incidence

Prevention programs:

• Tobacco• Alcohol

HPV:

• Vaccination??

Decreasing mortalityDiagnosis Treatment

Continued Education Programs:

• General practitioners• Dentists

Screening procedures???:

• Targeted poulations

Increase access:

• Inclusion to clinical trials.

• Increase government programs.

• Awareness to cancer associations.

GRACIAS