Cáncer de pulmón Panorama sobre su impacto, retos y necesidades actuales de atención

Oscar Arrieta MD Unidad Funcional de Oncología Torácica

Instituto Nacional de Cancerología

Noviembre 2015

Diez principales neoplasias en el mundo - GLOBOCAN 2008

Jemal A. Global Cancer Facts &Figures 2008

Pulmón Mama Colorrectal Estómago Próstata Hígado Cérvix Esófago Vejiga Linfomas Otros

n=12,667,500 nuevos casos

12.7%

10.9%

9.73%

7.81%

7.13% 5.9%

Países Desarrollados

Países en desarrollo

Cáncer Pulmonar: PROBLEMA DE SALUD PÚBLICA MUNDIAL

Primera causa de muerte por cáncer

1.6 millones de casos nuevos anualmente

1.2 millones de muertes anuales

~15% viven a 5 años

Muertes diarias: >3,000

Enfermedad avanzada: viven 10-12 meses

From: The Global Burden of Cancer 2013

JAMA Oncol. Published online May 28, 2015. doi:10.1001/jamaoncol.2015.0735

Age-Specific Global Contributions of Cancer Types to Total Cancer Incidence and Mortality, 2013For International Classification of Diseases codes included in the other neoplasms

group, see eTable 15 in the Supplement.

Figure Legend: FFFFFFFFFFFFFiiiiiiiiiiiiiggggggggggguuuuuuuuuuurrrrrrrrrreeeeeeeeee LLLLLLLLLLLLLLLeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeggggggggggggggggggeeeeeeeeeeeeeennnnnnnnnnnnnndddddddddddddddddddddddddddddddddddddddddd::::::::::::::

The Global Burden of Cancer 2013, Jama-oncol

Date of download: 7/2/2015 Copyright © 2015 American Medical Association. All rights reserved.

From: The Global Burden of Cancer 2013

JAMA Oncol. Published online May 28, 2015. doi:10.1001/jamaoncol.2015.0735

Trends in Age-Standardized Incidence Rates for Tracheal, Bronchus, and Lung Cancer, 1990-2013

Figure Legend:

Distribución porcentual de las defunciones por tumores malignos para cada sexo (2006-2007)

Mortalidad

Sobrevida en pacientes tratados con quimioterapia

Median OS: 8 months

N=1007

Lung Cancer Mutation Consortium LCMC

Mutations/gene alterations identified in >60% of cases

Johnson B, et al. ASCO 2013. Abstract 8019.

Mutación + Terapia Blanco (n = 313) Mutación + no terapia blanco (n = 265) Sin mutaciones Tx con QT (n = 361) 100

80

60

40

20

0

Supe

rviv

enci

a G

loba

l (%

)

0 1 2 3 4 5 Años

Beneficios de las terapias blanco: SVG de acuerdo a mutaciones y terapia recibida

The Jackson Laboratory – West UC Davis Cancer Center ••Center for Advanced Preclinical Research, NCI

EGFR Mutation status per ethnicity

Geographical and ethnic frequencies of epidermal growth factor receptor mutations

Frequency Country

19% Korea

32-56% Japan

55-61% Taiwan

18% Italy

6.8-2’% USA

14% Non-Hispanic Whites

2.4% African-Americans

12% Spain

Latin America N= 4,136 Positive 6.09% (252)

Negative 93.91% (3,884)

FISH- ALK in Non-Small Cell Lung Cancer

Colombia 4.1%

(10/242)

Chile 5.2% (5/94)

Argentina 6.1%

(153/2491)

Uruguay 5.3% (2/37)

Panama 4.4%

(5/114)

Mexico 8.3%

(64/769)

Costa Rica 8.7%

(13/137)

Mexico 486/1417 (EGFR (34.3)

Colombia 479/1939 (EGFR (24.7))

Argentina 247/1713 (EGFR 14.4%)

Perú 201/393 (EGFR 51.1%)

Number of patients 5738 Mutation Rate 1491 (26.0%) (95%CI: 25.3-26.7)

Costa Rica 32/102 (31.4)

Panama 47/174 (27.3)

Arrieta et al, J Thorac Oncol. 2011 Nov;6(11):1955-9

The Jackson Laboratory – West UC Davis Cancer Center ••Center for Advanced Preclinical Research, NCI

Figure 2. Clinical and epidemiological differences among NSCLC by gender

NSCLC Mutation EGFR

Sharma SV, et al. Nature Rev Cancer 2007;7;169–181; Ji H, et al. Proc Natl Acad Sci USA 2006;103;7817–7822

180 patients

Mexico Costa Rica Colombia

The impact of common and rare EGFR mutations

uncommon EGFR mutations

APC T cell

Activation (cytokines, lysis, prolif.,

migration)

B7.1 CD28

TCR Signal 1 MHC-Ag

Tumor

INMUNOTERAPIA

r ME et al, Annu Rev Immunol 2008; Pardoll DM, Nat Rev Cancer 20

APC T cell

Activation (cytokines, lysis, prolif.,

migration)

B7.1 CD28

TCR Signal 1 MHC-Ag

Tumor

INMUNOTERAPIA

Tumor PD-L1 PD-1

r ME et al, Annu Rev Immunol 2008; Pardoll DM, Nat Rev Cancer 20

(-) (-) (-)

Inhibition (anergy, exhaustion, death)

APC T cell

Activation(cytokines, lysis, prolif.,

migration)

B7.1 CD28

TCR Signal 1 MHC-Ag

Tumor

INMUNOTERAPIA

Tumor PD-L1 PD-1

r ME et al, Annu Rev Immunol 2008; Pardoll DM, Nat Rev Cancer 20

(-) (-) (-)

Inhibition (anergy, exhaustion, death)

Anti-PD-1

Costos del Tratamiento del Cáncer Pulmonar

Avances en el Tratamiento actual…

¿Y el costo de los

Tratamiento?

Arrieta et al. Tobacco Induced Diseases (2014) 12:25

Lopes et al, Nat Rev Clin Oncol. 2013 Jun;10(6):314-22.

By 2008: 63% global deaths due to noninfectious maladies

Cancer: 7.1 million deaths

80% Low-and Middle-income countries

Main cause of lost life years and productivity

Initiative Benefits Challenges Access to care Universal health-care coverage Pooling of resources

Financial protection Financing through taxation or contrivution in areas with low resources Rising health-care costs and expenditures once enacted Lawsuits against the state or government when drugs are not supplied

Genetic drugs and biosimilars Lower cost of drugs through increased competition Increased Access

Public and health-care worker perception on quality Regulatory pathways for biosimilars are still uncertain in many jurisdictions

Compulsory Licensing Early introduction of generic drug competition

Might lead to trade sanctions and decreased incentives for innovation

Research Participation in clinical trials and research

Access to standard and research medications and treatments that might not be widely available because of high cost

Ethical issues include the adequacy of informed consent, independent review and oversight, ethnic differences and conflicts of interest

Drug development in emerging Lower cost of development might Regulatory scrutiny seems less

Initiative Benefits Challenges New payment methods Price discrimination Companies expand the number of

customers who are able to afford its products Successful distribution of medications in the developing world

Parallel imports can lead to decreased profits in higher paying markets, political backlash because of lower prices in other jurisdictions and perceived inequity

Access Programs Companies expand the number of customers who are able to afford its products

Parallel importing

Risk-sharing agreements Decreases overall costs as no payment is made for patients who do not benefit from drug

Complexity, lack of consensus on end point and definiotion of benefit

Cooperation among stakeholders Health technology assessments Pricing process for a new

medications is objective and attuned to its clinical and economic benefit

Complexity, lack of agreement for universal willingness-to-pay threshold

Public-private partnerships and philantrhopy

Multiple stakeholder involvement and sources of finance

Often haphazard, leading to wasted efforts Sometimes unsustainable in the l t

Investigación independiente vs Industria Estudios clínicos de oncología regristados en clinicaltrials

EUA Brasil México

Registrados 20,749 (100%) 539 (100%) 340 (100%)

Activos 6,743 (32%) 186 (34.5%) 114 (33.5%)

Industria 7,268 (35%) 404 (74.9%) 285 (83.8%)

NIC 8,127 (39%) 118 (21.9%) 48 (14.1%)

Otros 5,327 (25.6%) 19 (3.5%) 8 (2.4%)

The Jackson Laboratory – West UC Davis Cancer Center ••Center for Advanced Preclinical Research, NCI

Importancia de desarrollar investigación independiente

– Mejorar el pronóstico del paciente

– Obtención de recursos para el tratamiento oncológico

– Evaluar objetivamente nuestros resultados

– Obtención de resultados de NUESTRA población

Pacientes en proyectos de investigación No Proyectos de investigación

ECOG 0-2 Estadio IV

INCAN 2002-2012 >900 pacientes

INCAN 2007-2013

Disease Stage II 0.6 (8/1260) IIIa 4.8 (60/1260) IIIb 18.4 (231/1260) IV 76.3 (961/1260) ECOG PS 0-1 73.2 (922/1260) 2-4. 26.8 (338/1260) Histology Adenocarcinoma 76.3 (961/1260) Epidermoid 13.3 (167/1260) Large Cell Carcinoma 3.3 (41/1260) Undifferentiated and others NSCLC 7.2 (91/1260) Carcinoembrionic antigen Mean 154.3 Median CNS metastases at diagnosis No 52.8 (675/1260) Yes 47.2 (585/1260)

EUA 2009

Diferencias en estadiaje Cáncer de pulmón

NLST: Estudio clínico aleatorizado

Tiempo

0 1 2 3 4 5 6 7 8

53,476 Personas alto riesgo

Brazo TAC

Brazo Rx

Aleatorizados

Seguimiento

T0

T1

T2

Oscar Arrieta

Apoyo de la Cámara de Diputados Comisión de Igualdad de Genero

“Programa de Apoyo a Mujeres No Fumadoras con Cáncer de Pulmón”

Trabajo con organizaciones

• Instituto Nacional de Cancerología • Gobierno • ONG

– RESPIRANDO CON VALOR – SOLO POR AYUDAR – SOCIEDAD MEXICANA DE ONCOLOGIA – CIENCIA QUE SE RESPIRA – AYUDA MESOTELIOMA, A.C. – ASOCIACIÓN MEXICANA DE LUCHA CONTRA EL

CÁNCER A.C.

Sobrevida a 1 año

Meses

Sob

revi

da

Supervivencia de 93.6% de

pacientes a 12 meses

Progresión a 1 año

Paci

ente

s (%

)

Progresión de la enfermedad (Meses)

Progresión en sólo 10.6% de pacientes

a 12 meses

Recursos aplicados a pacientes

Feb Mar Abr May Jun Jul Ago Sep Oct Nov Dic Recursos (mill) 17.5 17.1 16.5 16.0 15.3 14.0 12.7 8.0 5.6 2.9 - Pacientes - 11 18 18 25 43 46 54 60 66 74

0

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40

50

60

70

80

0

2

4

6

8

10

12

14

16

18

20

Peso

s (m

illon

es)

Costos por paciente

Mar Abr May Jun Jul Ago Sep Total por paciente $36,185 $31,982 $31,755 $30,193 $37,899 $28,045 $28,816 Medicamentos por paciente $21,639 $20,688 $20,084 $22,062 $22,062 $23,159 $24,830 Recursos humanos por paciente $14,545 $11,294 $11,671 $8,132 $5,002 $4,885 $3,986

$0

$5,000

$10,000

$15,000

$20,000

$25,000

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$35,000

$40,000

Peso

s

Agradecimiento

• Gracias al apoyo de la comisión de equidad y género de la cámara de diputados otorgado en Enero del 2015 a la Unidad Funcional de Oncología Torácica y Laboratorio de Medicina Personalizada del Instituto Nacional de Cancerología.

The Jackson Laboratory – West UC Davis Cancer Center ••Center for Advanced Preclinical Research, NCI

Victory at all costs, victory in spite of all terror, victory

however long and hard the road may be; for without

victory, there is no survival.

Winston Churchill