Cáncer de pulmón.

Noviembre 2015
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
Diez principales neoplasias
en el mundo - GLOBOCAN 2008
n=12,667,500 nuevos casos
Pulmón
12.7%
Mama
Colorrectal
10.9%
Estómago
Próstata
9.73%
Hígado
Cérvix
7.81%
Esófago
Vejiga
5.9% 7.13%
Linfomas
Otros
Jemal A. Global Cancer Facts &Figures 2008
Cáncer Pulmonar: PROBLEMA DE SALUD PÚBLICA MUNDIAL
Países
Desarrollados
Países en
desarrollo
Primera causa de muerte por cáncer
1.6 millones
anualmente
de
casos
nuevos
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
Figure
F
igure Legend:
Legend:
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.
The Global Burden of Cancer 2013, Jama-oncol
From: The Global Burden of Cancer 2013
JAMA Oncol. Published online May 28, 2015. doi:10.1001/jamaoncol.2015.0735
Figure Legend:
Trends in Age-Standardized Incidence Rates for Tracheal, Bronchus, and Lung Cancer, 1990-2013
Date of download: 7/2/2015
Copyright © 2015 American Medical
Association. All rights reserved.
Distribución porcentual de las defunciones por tumores malignos para cada sexo
(2006-2007)
Mortalidad
Sobrevida en pacientes tratados con
quimioterapia
Median OS: 8 months
Lung Cancer Mutation Consortium
LCMC
N=1007
Mutations/gene alterations identified in >60% of cases
Beneficios de las terapias blanco:
SVG de acuerdo a mutaciones y terapia recibida
Mutación + Terapia Blanco (n = 313)
Mutación + no terapia blanco (n = 265)
Sin mutaciones Æ Tx con QT (n = 361)
Supervivencia Global (%)
100
80
60
40
20
0
0
1
2
3
4
5
Años
Johnson B, et al. ASCO 2013. Abstract 8019.
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
Center for Advanced Preclinical Research, NCI
•
The Jackson Laboratory – West
•
UC Davis Cancer
Center
FISH- ALK in Non-Small Cell Lung
Cancer
Latin America N= 4,136
Positive 6.09% (252)
Negative 93.91% (3,884)
Panama
4.4%
(5/114)
Mexico
8.3%
(64/769)
Colombia
4.1%
(10/242)
Uruguay
5.3%
(2/37)
Costa Rica
8.7%
(13/137)
Chile
5.2%
(5/94)
Argentina
6.1%
(153/2491)
Number of patients 5738 Mutation Rate
1491 (26.0%) (95%CI: 25.3-26.7)
Mexico 486/1417
(EGFR (34.3)
Costa Rica
32/102 (31.4)
Panama
47/174 (27.3)
Colombia 479/1939
(EGFR (24.7))
Perú 201/393
(EGFR 51.1%)
Argentina 247/1713
(EGFR 14.4%)
Arrieta et al, J Thorac Oncol. 2011 Nov;6(11):1955-9
Figure 2. Clinical and epidemiological differences among NSCLC by gender
Center for Advanced Preclinical Research, NCI
•
The Jackson Laboratory – West
•
UC Davis Cancer
Center
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
INMUNOTERAPIA
APC
T cell
B7.1
MHC-Ag
Activation
(cytokines, lysis, prolif.,
migration)
CD28
TCR Signal 1
Tumor
r ME et al, Annu Rev Immunol 2008; Pardoll DM, Nat Rev Cancer 20
INMUNOTERAPIA
APC
T cell
B7.1
MHC-Ag
Activation
(cytokines, lysis, prolif.,
migration)
CD28
TCR Signal 1
(-)
(-)
(-)
PD-1
PD-L1
Tumor
Inhibition
Tumor
(anergy, exhaustion, death)
r ME et al, Annu Rev Immunol 2008; Pardoll DM, Nat Rev Cancer 20
INMUNOTERAPIA
APC
T cell
B7.1
MHC-Ag
Activation
(cytokines, lysis, prolif.,
migration)
CD28
TCR Signal 1
(-)
(-)
(-)
AntiPD-1
PD-1
PD-L1
Tumor
Inhibition
Tumor
(anergy, exhaustion, death)
r ME et al, Annu Rev Immunol 2008; Pardoll DM, Nat Rev Cancer 20
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
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
Lopes et al, Nat Rev Clin Oncol. 2013 Jun;10(6):314-22.
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 Might lead to trade sanctions and
competition
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
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 Parallel importing
customers who are able to afford
its products
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
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
New payment methods
Cooperation among stakeholders
Investigación independiente vs Industria
Estudios clínicos de oncología regristados en clinicaltrials
EUA
Brasil
México
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%)
5,327 (25.6%)
19 (3.5%)
8 (2.4%)
Registrados
Otros
Importancia de desarrollar investigación
independiente
– Mejorar el pronóstico del
paciente
– Obtención de recursos para el
tratamiento oncológico
Pacientes en proyectos de investigación
No Proyectos de investigación
– Evaluar objetivamente
nuestros resultados
– Obtención de resultados de
NUESTRA población
Center for Advanced Preclinical Research, NCI
•
ECOG 0-2
Estadio IV
INCAN 2002-2012
>900 pacientes
The Jackson Laboratory – West
•
UC Davis Cancer
Center
Diferencias en estadiaje
Cáncer de pulmón
INCAN
2007-2013
EUA 2009
Disease Stage
II
IIIa
IIIb
IV
ECOG PS
0-1
2-4.
Histology
Adenocarcinoma
Epidermoid
Large Cell Carcinoma
Undifferentiated and
others NSCLC
Carcinoembrionic antigen
Mean
Median
CNS metastases at
diagnosis
No
Yes
0.6 (8/1260)
4.8 (60/1260)
18.4 (231/1260)
76.3 (961/1260)
73.2 (922/1260)
26.8 (338/1260)
76.3 (961/1260)
13.3 (167/1260)
3.3 (41/1260)
7.2 (91/1260)
154.3
52.8 (675/1260)
47.2 (585/1260)
NLST: Estudio clínico aleatorizado
Brazo TAC
Seguimiento
53,476
Personas Aleatorizados
alto riesgo
Brazo Rx
T1
Tiempo
0
1
T0
2
3
T2
4
5
6
7 8
“Programa de Apoyo a Mujeres No Fumadoras
con Cáncer de Pulmón”
Oscar Arrieta
Apoyo de la Cámara de Diputados
Comisión de Igualdad de Genero
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
Sobrevida a 1 año
Supervivencia de
93.6% de
pacientes a 12
meses
Meses
Pacientes (%)
Progresión a 1 año
Progresión en sólo
10.6% de pacientes
a 12 meses
Progresión de la enfermedad
(Meses)
Recursos aplicados a pacientes
20
80
18
70
Pesos (millones)
16
60
14
50
12
10
40
8
30
6
20
4
10
2
0
Recursos (mill)
Pacientes
Feb
17.5
-
Mar
17.1
11
Abr
16.5
18
May
16.0
18
Jun
15.3
25
Jul
14.0
43
Ago
12.7
46
Sep
8.0
54
Oct
5.6
60
Nov
2.9
66
Dic
74
0
Costos por paciente
$40,000
$35,000
$30,000
Pesos
$25,000
$20,000
$15,000
$10,000
$5,000
$0
Total por paciente
Medicamentos por paciente
Recursos humanos por paciente
Mar
$36,185
$21,639
$14,545
Abr
$31,982
$20,688
$11,294
May
$31,755
$20,084
$11,671
Jun
$30,193
$22,062
$8,132
Jul
$37,899
$22,062
$5,002
Ago
$28,045
$23,159
$4,885
Sep
$28,816
$24,830
$3,986
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.
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
Center for Advanced Preclinical Research, NCI
•
The Jackson Laboratory – West
•
UC Davis Cancer
Center