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¿Cómo se trata el cáncer gástrico avanzado
en América Latina?
¿Cómo podemos reducir la carga de la
enfermedad?
Moderador:
Manny Papadimitropoulos PhD
Lider Cientifico de Resultados en Salud, America Latina, Eli Lilly & Company y
Profesor Adjunto, Facultad de Farmacia, Universidad de Toronto, CANADA
Ponentes:
Dr. Jorge Gallardo, Oncólogo, Clínica Alemana
Santiago, Presidente de SLAGO, Santiago, Chile
Dr. Joao Paulo Reis Neto, Coordinador Ejecutivo,
Groupo de Implementation de Technologias, CAPESESP,
Rio de Janeiro, Brazil
Dr. Germán Calderillo Ruiz, Coordinador de la
Unidad Funcional Gastro-Oncologia del Instituto
Nacional de Cancerologia, Mexico City, Mexico
1
EPIDEMIOLOGÍA Y RESULTADOS DE SOBREVIDA DE
CÁNCER GÁSTRICO EN AMÉRICA LATINA
Dr. Jorge Gallardo E.
Oncólogo
Clínica Alemana Santiago
Santiago, Chile
EPIDEMIOLOGÍA Y RESULTADOS DE SOBREVIDA DE
CÁNCER GÁSTRICO EN AMÉRICA LATINA
GENERALIDADES
EPIDEMIOLOGÍA DEL CÁNCER GÁSTRICO EN LATINOAMÉRICA
FACTORES DE RIESGO DE CÁNCER GÁSTRICO
HELICOBACTER PYLORI EN CÁNCER GÁSTRICO
RESULTADOS DE SOBREVIDA EN LATINOAMERICA
INCIDENCIA Y MORTALIDAD DE CÁNCER GASTRICO SE PUEDE DISMINUIR
2
CÁNCER GÁSTRICO
Generalidades
•
4to cáncer más común a nivel mundial
•
Segunda causa de mortalidad.
•
Tasas de incidencia y mortalidad son altas en países menos desarrollados.
•
Dos tercios de las muertes por cáncer gástrico ocurre fuera de los países
con altos ingresos.
•
Latinoamérica:
– Cáncer gástrico predomina frente a otros tipos de cánceres
– Algunos países lideran las tasas de mortalidad mundial.
Cancer Causes Control, 2013 Feb: 24(2):217-231
CÁNCER GÁSTRICO
Generalidades
Diagnóstico de cáncer gástrico:
•
Falta de síntomas específicos tempranos
– Pacientes no consultan
– Si paciente consulta a veces no se realizan los exámenes pertinente
•
Mayoría de los pacientes son diagnosticados después del cáncer ha
invadido la muscular propia Cambio importante en pronóstico
•
Tasa de sobrevida a 5 años para el cáncer gástrico en los Estados Unidos es
de menos del 30% .
– Pero 8% de pacientes en etapa IV si están vivos a 5 años
3
EPIDEMIOLOGÍA Y RESULTADOS DE SOBREVIDA DE
CÁNCER GÁSTRICO EN AMÉRICA LATINA
GENERALIDADES
EPIDEMIOLOGÍA DEL CÁNCER GÁSTRICO EN LATINOAMÉRICA
FACTORES DE RIESGO DE CÁNCER GÁSTRICO
HELICOBACTER PYLORI EN CÁNCER GÁSTRICO
RESULTADOS DE SOBREVIDA EN LATINOAMERICA
INCIDENCIA Y MORTALIDAD DE CÁNCER GASTRICO SE PUEDE DISMINUIR
CÁNCER DE ESTÓMAGO: INCIDENCIA Y MORTALIDAD
LATINOAMÉRICA, AMBOS SEXOS - 2012
Tasas mortalidad
muy cercana a
tasa de incidencia
Área andina y
Centro América
Tienen mayor
tasa de incidencia
y tasa de mortalidad
Existen «zonas-focos»
de mayor incidencia
GLOBOCAN 2012
4
Mortalidad por Cáncer Gástrico
en América Latina (1980-2010)
México
Argentina
Colombia
Chile
Peru
Costa Rica
Número de muertes (100,000)
PROYECCIONES DE MORTALIDAD POR CÁNCER SEGÚN
ÓRGANOS LATINOAMÉRICA Y EL CARIBE
SEGÚN OPS/PAHO
1.4
1.2
1.0
Estómago
0.8
Hígado
0.6
Colon
0.4
cervical
Mamas
0.2
0
2002
2005
2015
2030
año
http://www.who.int/healthinfo/statistics/
5
EPIDEMIOLOGÍA Y RESULTADOS DE SOBREVIDA DE
CÁNCER GÁSTRICO EN AMÉRICA LATINA
GENERALIDADES
EPIDEMIOLOGÍA DEL CÁNCER GÁSTRICO EN LATINOAMÉRICA
FACTORES DE RIESGO DE CÁNCER GÁSTRICO
HELICOBACTER PYLORI EN CÁNCER GÁSTRICO
RESULTADOS DE SOBREVIDA EN LATINOAMERICA
INCIDENCIA Y MORTALIDAD DE CÁNCER GASTRICO SE PUEDE DISMINUIR
FACTORES DE RIESGO
ASOCIADOS CON CÁNCER GÁSTRICO
+
+
-
Protective F: Education
Fruits
Vegetables
Risk Factors: Current smoking
Alcohol use
Cancer Causes Control, 2013 Feb: 24(2):217-231
6
FACTORES DE RIESGO
ASOCIADOS CON CÁNCER GÁSTRICO (Cont)
+
+
+
+
+
Protective F: 0
Risk Factors: Processed or salted meat
Table salt used
genotipo IL1RN VNTR
Cancer Causes Control, 2013 Feb: 24(2):217-231
FACTORES DE RIESGO
ASOCIADOS CON CÁNCER GÁSTRICO (Cont)
Meta-análisis de estudios latinoamericanos identificaron:
•
Aumento de los riesgos de cáncer gástrico asociadas con :
–
–
–
–
•
Tabaquismo
Consumo de alcohol
Consumo elevado de carne roja y procesada
Ingesta excesiva de sal y el transporte de IL1RN * 2
Disminución de riesgos con:
– Alto nivel de educación
– Alto consumo de frutas y vegetales.
Identificar factores de riesgo puede ayudar a determinar la etiología de la
enfermedad y sugerir estrategias de prevención.
Cancer Causes Control, 2013 Feb: 24(2):217-231
7
CÁNCER GÁSTRICO
Factores de Riesgo
•
•
Rol de H. Pylori
Principal causa mundial de cáncer
relacionada con infección en los
hombres y la segunda en las mujeres
después del cáncer de cuello uterino.
H.Pylori:
–
–
–
•
Colonización de la mucosa gástrica
Inflamación crónica de la mucosa
Desarrollo de lesiones pre-neoplásicas.
Factores de virulencia bacteriana:
–
–
–
Daño epitelial a través de las vías
inflamatorias
Generación de especies reactivas de
oxígeno y compuestos nitrosos
Inestabilidad del ADN.
Cancer Causes Control. 2013 Feb; 24(2): 249–256
CONCLUSIÓN - FACTORES DE RIESGO
•
Factores de riesgo para cáncer gástrico en América Latina son similares a los identificados a
nivel mundial.
•
Falta identificar factores de riesgo adicionales que contribuyen a la alta incidencia de cáncer
gástrico en América Latina.
•
Hay una relación negativa entre nivel educativo y socioeconómico y la incidencia de Cáncer
Gástrico
•
No hay pruebas suficientes para modificaciones en la dieta para prevenir el cáncer gástrico,
es necesario realizar modificaciones de estilo de vida para reducir el tabaquismo en esta
región geográfica.
•
Necesario evaluar simultáneamente otras morbilidades crónicas comunes como la diabetes,
la obesidad y las enfermedades cardiovasculares.
•
Resolver el enigma de la alta incidencia de cáncer gástrico en América Latina reduciría la
mortalidad en esta región y podría mejorar nuestra comprensión de la etiología del cáncer.
Cancer Causes Control, 2013 Feb: 24(2):217-231
8
EPIDEMIOLOGÍA Y RESULTADOS DE SOBREVIDA DE
CÁNCER GÁSTRICO EN AMÉRICA LATINA
GENERALIDADES
EPIDEMIOLOGÍA DEL CÁNCER GÁSTRICO EN LATINOAMÉRICA
FACTORES DE RIESGO DE CÁNCER GÁSTRICO
HELICOBACTER PYLORI EN CÁNCER GÁSTRICO
RESULTADOS DE SOBREVIDA EN LATINOAMERICA
INCIDENCIA Y MORTALIDAD DE CÁNCER GASTRICO SE PUEDE DISMINUIR
ESTANDAR DE AÑOS DE SUPERVIVENCIA EN ADULTOS
ENTRE 15 - 99 AÑOS EN AMERICA LATINA
9
CANCER GASTRICO, ESTANDAR DE AÑOS DE SUPERVIVENCIA EN
ADULTOS ENTRE 15 - 99 AÑOS EN AMERICA LATINA
• América Latina tiene tasas de sobrevida a 5 años muy
inferiores a EEUU y Europa
• Descenso de tasas de sobrevida en Brasil y Argentina
• Tasas más altas de sobrevida en Ecuador, Cuba y P. Rico
• Gran parte de datos de L.A. son sólo de registros parciales.
En EE UU y Europa son datos nacionales
CANCER GASTRICO, ESTANDAR DE AÑOS DE SUPERVIVENCIA EN
ADULTOS ENTRE 15 - 99 AÑOS EN AMERICA LATINA
• Tasa de peor sobrevida podrían explicarse por:
– Diagnóstico tardío;
– Atención en centros no especializados
 Falla selección de pacientes
 cirugía no óptima,
 Carencia de Unidad Cuidados Intensivos óptimas
– no uso de terapias adyuvantes
– no uso de quimioterapia en enfermedad metastásica
– Falta de estudios clínicos
– FALTA DE POLITICA APROPIADAS
•
•
•
•
Desplazada por recursos económicos
Enfermedad compleja de abordar
Carencia de conocimiento en gobierno
AUSENCIA DE PACIENTES QUE EXIGEN SUS DERECHOS DE TERAPIA
10
EPIDEMIOLOGÍA Y RESULTADOS DE SOBREVIDA DE
CÁNCER GÁSTRICO EN AMÉRICA LATINA
GENERALIDADES
EPIDEMIOLOGÍA DEL CÁNCER GÁSTRICO EN LATINOAMÉRICA
FACTORES DE RIESGO DE CÁNCER GÁSTRICO
HELICOBACTER PYLORI EN CÁNCER GÁSTRICO
RESULTADOS DE SOBREVIDA EN LATINOAMERICA
INCIDENCIA Y MORTALIDAD DE CÁNCER GASTRICO SE PUEDE DISMINUIR
CÓMO DISMINUIR LA MORTALIDAD POR CÁNCER
GÁSTRICO? (primera causa de muerte por cáncer)
1.– DISMINUIR La INCIDENCIA Disminución de sal y las comida quemadas
erradicación H. Pylori
2.- DESARROLLAR SCREENING En población de riesgo elevado, área de riesgo elevado
3.-Mejorar el Dg
Aumentar la evaluación endoscópica
4.- Mejorar la calidad cirugía
Hecha por cirujanos entrenados,
Realizada en algunos centros
5.- Indicación Tx ADJUVANTES Quimio Perioperatoria
Radio-Chtx seguido de quimiotx.
6.- Terapia de Enf Sistémica
Quimioterapia
Pacientes deben ser evaluados por equipo multidisciplinarios antes de iniciar tratamiento,
11
CÓMO DISMINUIR LA MORTALIDAD POR CÁNCER
GÁSTRICO? (Primera causa de muerte por cáncer)
Bonus Track
12
Cardias GE Junction
Are increasing
Pylorus and Antrus GC
Are decreasing
MINISTERIO DE SALUD. Guía Clínica CÁNCER GÁSTRICO. SANTIAGO: Minsal, 2010.
13
GRACIAS
¿Preguntas?
Economic aspects of gastric
cancer in Latin America
João Paulo dos Reis Neto
HOW IS ADVANCED GASTRIC CANCER TREATED IN LATIN AMERICA? HOW CAN WE REDUCE THE BURDEN OF THE DISEASE?
14
Incidence, mortality, 5-year prevalence - World
Incidence – 5th
+ 1 million
Mortality – 3th
Prevalence – 6th
Incidence, mortality, 5-year prevalence - World
Incidence – 6th
44,000, half in
Brazil
Mortality – 3th
Prevalence – 6th
15
Age-standardised rate per 100,000 – incidence and mortality
70% occur in developing countries, half in Asia (China)
16
5-year prevalence and incidence
Ratio mortality /
incidence (MI) 0.70
17
Gastric Cancer - Brazil - 2015
395,000 new cases of cancer¹ (without skin non
melanoma); 13.19 / 7.41 per 100,000 men
and women, respectively
2th men (11.10 / 100,000)
3rd women (5.91)
4th men (10.25 / 100,000)
5th women (6.39)
4th men (10.88 / 100,000)
6th women (6.32)
5th men (14.99 / 100,000)
5th women (8.20)
4th men (16.07 / 100,000)
6th women (8.43)
¹ INCA – National Institute of Cancer, Brazil
North
Northeast
Central Region
Southeast
South
Cost-effectiveness of screening and treating
Helicobacter pylori for gastric cancer prevention
• A meta-analysis of seven randomized controlled trials
concluded that eradication of Helicobacter pylori reduces
the incidence of gastric cancer by 35%;
• The current consensus is that the screening and treatment
of H. pylori is cost effective only in high-risk populations;
• They were identified ten analysis of cost-effectiveness or
cost -utility. Everyone thought that screening for H. pylori to
prevent gastric cancer in the general population costs less
than $ 50,000 per year of life gained.
Best Pract Res Clin Gastroenterol. 2013 Dec;27(6):933-47. doi: .1016/j.bpg.2013.09.005. Epub 2013 Sep 27. Cost-effectiveness of
screening and treating Helicobacter pylori for gastric cancer prevention. Lansdorp-Vogelaar I1, Sharp L.
18
Gastric cancer: real world data - Brazilian health plan
Invasive tests (endoscopy with biopsy + urease)
3,100 tests / 100,000 patients
U$ 98
Non invasive (breathing 30%)
450 / 100,000 patients
U$ 10
HOW IS ADVANCED GASTRIC CANCER TREATED IN LATIN AMERICA? HOW CAN WE REDUCE THE BURDEN OF THE DISEASE?
Eradication of Helicobacter pylori –
estimated cost in Brazil
• 1St line peptic ulcer - pantoprazole 40 mg, clarithromycin 500
mg and amoxicillin 1.0 g twice daily for 7 days¹ (efficacy 87%
per protocol analysis and 84.5%in the intention-to-treat
analysis);
U$ 40-50
St
• 1 line – lansoprazole 30 mg, clarithromycin 500 mg and
amoxicillin 1.0 g twice daily for 10 days² (efficacy 91.3% ITT
analysis)
U$ 50-60
St
• 2 line (retreatement) - lansoprazole 30 mg, levofloxacino 250
mg, furazolidona 200 mg twice daily for 7 days³ (89.4% PP,
87.5%in ITT);
U$ 30-40
1 - COELHO, Luiz Gonzaga Vaz et al . Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg, twice daily for 7 days, in
the eradication of Helicobacter pylori in patients with peptic ulcer. Arq. Gastroenterol., São Paulo , v. 41, n. 1, p. 71-76, Mar. 2004
2 - Mazzoleni LE, Sander GB, Ott EA, Barros SG, Francesconi CF, Polanczyk CA, et al. Clinical outcomes of eradication of Helicobacter pylori in nonulcer dyspepsia in a
population with a high prevalence of infection: results of a 12-month randomized, double blind, placebo-controlled study. Dig Dis Sci. 2006 Jan51(1):89-98.
3 - Eisig JN et al. Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication.BMC Gastroenterology 2009,
9:38
19
3rd BRAZILIAN CONSENSUS ON Helicobacter pylori
GROUP 2. H pylori, GASTRIC ADENOCARCINOMA AND MALT LYMPHOMA
COELHO, Luiz Gonzaga et al . 3rd BRAZILIAN CONSENSUS ON Helicobacter pylori.Arq. Gastroenterol., São Paulo , v. 50, n. 2, p. 81-96, June 2013.
Available from <http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-28032013000200081&lng=en&nrm=iso>. access
on 25 Aug. 2015. Epub Apr 19, 2013. http://dx.doi.org/10.1590/S0004-28032013005000001.
3rd BRAZILIAN CONSENSUS ON Helicobacter pylori
GROUP 2. H pylori, GASTRIC ADENOCARCINOMA AND MALT LYMPHOMA
COELHO, Luiz Gonzaga et al . 3rd BRAZILIAN CONSENSUS ON Helicobacter pylori.Arq. Gastroenterol., São Paulo , v. 50, n. 2, p. 81-96, June 2013.
Available from <http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-28032013000200081&lng=en&nrm=iso>. access
on 25 Aug. 2015. Epub Apr 19, 2013. http://dx.doi.org/10.1590/S0004-28032013005000001.
20
Gastric Cancer - Drugs
•
•
•
•
•
•
•
Platinoids
Fluorouracil
Doxorubicin Hydrochloride
Mitomycin C
Ramucirumab*
Trastuzumab
Taxanes
* Recently approved by the European Union, Japan, Mexico and the United
States for the second-line treatment of gastric cancer
Cost of Gastric Cancer in the United States
•
•
•
•
•
Retrospective cohort analysis of direct costs and utilization of health services
in gastric cancer patients and controls was performed using the IMS database
(LifeLink Claims);
Controls were individuals without gastric cancer, matched 1: 1 with the cases
(98.4%) in age, gender, region, health insurance and type of payer, and followup;
A total of 303 cases were identified and matched with control. In both groups,
the mean age was 58 years, 55% were male and the median follow-up was 364
days;
The average total monthly cost of care for patients with newly diagnosed
gastric cancer was 18 times higher than that of patients without gastric cancer;
The biggest difference was in hospital costs, followed by the cost of drugs and
imaging.
Estimating the economic burden of gastric cancer in the United States.J Clin Oncol 29: 2011 (suppl; abstr e16589). K. B. Knopf, D. B. Smith, J. F. Doan, J.
Munakata; California Pacific Medical Center, San Francisco, CA; IMS Health, Inc., Watertown, MA; Genentech Inc., South San Francisco, CA; IMS Health,
Redwood City, CA
21
Costs
• Patients without health insurance - the treatment of stomach
cancer costs up to $ 50,000 for surgery + costs with chemotherapy
and radiotherapy, reaching $ 200,000, depending on the case;
• Chemoradiotherapy after surgery for localized gastric cancer according to a study published in the Journal of Gastrointestinal
Cancer Research¹, costs about US $ 20,100;
• The average total monthly cost of care for a patient with newly
diagnosed gastric cancer, for the first year, including hospitalization,
doctor visits, laboratory, radiation and drugs is about US $ 10,600 /
month (almost $ 130,000 for one year ) ²;
• Cost-effectiveness analysis of Chemoradiotherapy for Adjuvant
Gastric Cancer resected: Cost of radiotherapy, chemotherapy and
toxicity management - US $ 8,999, US $ 4,943 and US $ 6,188 by
cycle respectively 3.
¹ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630819/
² http://meetinglibrary.asco.org/subcategories/2011+ASCO+Annual+Meeting
³ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630819/
Average costs of gastric cancer patients undergoing
chemotherapy (Medicare*)
1st-line therapy
treatment-related
Post 1st-line therapy
supportive care
treatment-related
$25,000
$25,000
$20,000
$20,000
$15,000
$15,000
$10,000
$10,000
$5,000
$5,000
supportive care
$0
$0
Multiple lines 1st-line only
of therapy
Multiple lines 1st-line only
of therapy
* Not including hospital admissions or clinic visits
Karve et al, J Gastric Cancer 2015
22
Gastric cancer: real world data - Brazilian health plan
M/W - 2:1
68 %
32 %
1-year survival rate – 57 %
Year
2010
2011
2012
2013
2014
Beneficiaries
150.172
145.885
132.595
127.556
114.278
Prevalence
35
37
47
41
33
Prop. 100,000
23,31
25,36
35,45
32,14
28,88
Gastric cancer: real world data - Brazilian health plan
Procedures
Visits
Exams
Hospitalizations
Others
Totals
Annual cost (in US $*)
1,541
47,736
401,711
210,810
661,799
US $ 15,000 / year, per patient
5 times more than the overall average without gastric cancer
54%
chemotherapy
US $ 29,924
per patient treated
* Annual cost in 2014; US $ 1 = R$ 3,20;
23
Conclusions
Gastric cancer is a devastating disease for
patients and costly for healthcare systems
Screening in high-risk patients and preventive
treatments (eg H. pylori) can bring value for
the money invested in health system
More research is needed in Latin America to
generate data on local costs for managing
this disease
Management of gastric cancer by new agents
can help prolong life and impact the quality of
life of patients
Joao Paulo dos Reis Neto
jpreis@mobilesaude.com.br
24
Role of innovative therapies for the
management of gastric cancer
September 6, 2015
Dr. Germán Calderillo Ruiz
calderillo06@yahoo.com.mx
Gastric Cancer
Percentage by Stage
China
(Shanghai)
AsiaPacific
Japon
(Mexico)
INCANn=506
N=7,342
n=2,075
N=12,644
(%)
(%)
(%)
(%)
0-I
3
15
40
59
II
14
23
13.8
11.3
III
23
24
19.3
14.7
IV
60
38
27.9
15
Stage
AP – Corea, Malasia, Filipinas, Taiwan, Tailandia
Gastric Cancer 2013
Asia Pac J Clin Oncol 2014
J Surg 2008
25
Gastric Cancer
Survival by stage
IA
IB
IIA
IIB
IIIA
IIIB
IIIC
IV
J Clin Oncol 2013;31:263-71
Key advances in the development of
gastric cancer therapeutics
1940-1950’s
1960-1970’s
1957
5-fluorouracil
Metotrexate
5-fluorouracil
1980 -1990’s
2000’s and beyond
Adriamicin
Trastuzumab
Etoposide
Lapatinib
Cisplatin
Ramucirumab
Docetaxel
Paclitaxel
Irinotecan
Capecitabine
“Today, chemotherapy has changed as important molecular abnormalities are being used to screen for
potential new drugs as well as for targeted treatments.”
DeVita et al. Cancer Res 2008; 68:8643-53.
26
New chemotherapy for gastric cancer can be linked to
extended survival for patients
Incremental innovation in gastric cancer
Median overall survival, month
14
12
BSC- Best support care
10
Fu -Fluorouracil
I
8
6
4
-Irinotecan
D
-Docetaxel
C
-Cisplatin
E
-Epirubicin
O
-Oxaliplatin
X
-Capecitabine
2
0
BSC
Cancer 1993;72:37-41
J Clin Oncol 2006;24:4991-7
N Eng J Med 2008;358:36-46
Fu
IF
DCF
CF
ECF
EOX
Ann Oncol 2008;19:1450-57
Nat Rev Clin Oncol 2014;11:10-21
Int J Cancer 2012;130:491-6
New chemotherapy for gastric cancer can be linked to
extended survival for patients
Incremental innovation in gastric cancer
Median overall survival, month
14
improvement of symptoms
12
10
8
6
4
2
Symptom
%
Reflux
60
Anorexia
65
Pain
68
Dysphagia
70
Vomiting
75
Weight
80
loss
0
BSC
Fu
IF
DCF
CF
ECF
EOX
Innovation therapeutics in gastric cancer has led to improvement in survival and
quality of life
27
Advanced Gastric Cancer
Innovative Therapies
molecular
 Overexpression of EGFR
Overexpression of HER2neu
Overexpression C-MET
 Anti-angiogenic Therapy
Gastroenterology 2011;141:476-85
Nature 2014;513:202-9
Innovative Therapies on Gastric Cancer
Study
Molecule
Patients
Result
ToGA
Trastuzumab
584
Positive
Regard
Ramucirumab
355
Positive
China-13
Apatinib
277
Positive
AVAGAST
Bevacizumab
760
Negative
EXPAND
Cetuximab
870
Negative
LOGIC
Lapatinib
454
Negative
REAL3
Panitumumab
730
Negative
TyTAN
Lapatinib
261
Negative
Granite
Everolimus
633
Negative
Eur J Cancer 2013;49:1565-7
28
HER2 IHC staining (3+)
Stomach cancer
UEG
UEG (n=43)
INCAN-Mexico
SMeO 2014
ESMO 2014
Overall
Men
Stomach (n=168)
18.6%
10.7%
8/37 (21.3%)
14/110 (12.7%)
0/6 (0%)
4/58 (6.9%)
Women
Images courtesy of F. Penault-Llorca, not to be reproduced without permission
TOGA – Overall survival in patients with
Gastric cancer – HER2-positive (IHC 3+/IHC2+Fish+)
In 1st line - Trastuzumab-5FU-Cisplatin vs 5FU-cisplatin
Van Cutsem et al. Lancet 2010;376:687-97
29
LOGIC - LAPATINIB
Advanced Gastric Cancer, n=545 (Her 2 neu – positive 3+)
In 1st line – CapeOx-placebo vs CapeOx-Lapatinib
Overall Survival
CapeOx – Capecitabine + Oxaliplatin
ROW – rest of the world
Lapa – lapatinib / Plac - placebo
ASCO GI 2013
New chemotherapy for gastric cancer can be linked to
extended survival for patients
18
16
14
12
10
8
6
4
2
0
EOX
Trial LOGIC/ Her 2neu (3+)
BSC
Trial ToGA / Her 2neu (3+)
BSC- Best supportive care
Chemotherapy
Median overall survival, month
Incremental innovation in gastric cancer
XP - T
Pacli-L
E
-Epirubicin
O
-Oxaliplatin
X
-Capecitabine
P
-Cisplatin
Pacli- Paclitaxel
T
-Trastuzumab
L
-Lapatinib
Incremental innovation in gastric cancer has led to improvement in survival
30
New chemotherapy for gastric cancer can be linked to
extended survival for patients
13 months
Trial LOGIC/ HER 2neu (3+)
Trial ToGA / HER 2neu (3+)
18
16
14
12
10
8
6
4
2
0
Chemotherapy
Median overall survival, month
Incremental innovation in gastric cancer
Selected population
BSC
EOX
XP - T
Pacli-L
Innovation therapeutics in gastric cancer has led to improvement in survival
Gastric Cancer
Stage IV - metastatic
Stage IV (%)
Mexico-Incan
60
North of Africa
57
India
50
Europa
42
Shangai
39
L-America
36
Asia-pacific
28
Japon
15
With the innovative therapy
the median survival
increases from 36 to 51%....
In 20% of the population with
stomach cancer stage IV
(HER 2 neu : positive 3+)
The most benefited population:
Asia
Gastric Cancer 2013
Asia Pac J Clin Oncol 2014
J Surg 2008
31
Gastric Cancer- Stage IV
Unidad Funcional Gastro-oncología – INCAN México
Gastric Cancer
Stage IV
N=802
(100%)
N=640 (80%)
Treatment with
con QT +/innovative therapy
N=240 (38%)
Second line
treatment
Incan - México
Gastric Cancer
Second line treatment with chemotherapy
Scheme
Media SV (m) p Value
Docetaxel
5.2
Placebo
3.6
Irinotecan
4.0
Placebo
2.4
< 0.05
<0.05
Eur J Cancer 2011;47:2306-14
J Clin Oncol 2012; 13:1513
32
Gastric cancer
Second line treatment with chemotherapy
Adverse Factors
HR
p Value
Activity level (ECOG)
1.79
0.008
Hb < 11.5
1.86
0.019
ACE > 50 ng/ml
1.86
0.004
Number of metastases > 2 sites
1.72
0.006
Time to progression < 6 months
1.97
0.0001
Br J Cancer 2008;99:1402-7
Innovative developments in therapy for gastric cancer
can be linked to extended survival for patients (2nd line)
12
7.2 months
8
6
p=0.035
P<0.05
p=0.01
0
P<0.05
2
P<0.05
4
4.5 months
10
P<0.05
Median overall survival, month
Incremental innovation in gastric cancer
P- paclitaxel
Incremental innovation in gastric cancer has led to improvement in survival
33
Ramucirumab in patients with metastatic gastric cancer
Impact on survival – 2nd line
(RAINBOW study)
HR (IC 95%) 0.776 (0.603-0.998)
P=0.047
HR (IC 95%) 0.807 (0.678-0.962)
P=0.0169
Ramucirumab (n=238)
Ramucirumab +Paclitaxel (n=330)
Placebo (n=117)
Placebo + paclitaxel (n=335)
Overall survival
Overall survival
(REGARD study)
1.4 months (37%)
5.2 m
3.8 m
months
9.6 m
2.3 months (30%)
7.4 m
months
Fuchs ChS. Lancet 2014;383:31-39
Wilke H. Lancet Oncol 2014;15:1224-35
Other innovative therapies in patients with metastatic gastric cancer
impact on survival – 2nd line
HR (IC 95%) 0.59 (0.37-0.93)
P=0.0176
HR (IC 95%) 0.62 (0.39-0.98)
P=0.0351
Lapatinib-Paclitaxel (n=52)
Apatinib (n=176)
Selected population
HER2 (3+)
14.0 m
7.6 m
Months
Taroh S. J Clin Oncol 2014;32:2039-2049
Placebo (n=91)
Overall survival
Overall survival
Paclitaxel (n=49)
Months
ESMO 2014
34
Innovative therapies in patients with metastatic gastric cancer
impact on survival – 2nd line
2nd line
1st line
Gastric Cancer
Stage IV
N=802
N=640 (80%)
Treatment with
Chemotherapy +/Innovative therapy
SV median 8 months (3-20)
N=240 (38%)
Received treatment
in 2nd line
SV median 6 months (2-6)
Incan - México
Pharmaceutical innovation has increased the
likelihood of survival for patients with cancer
Novel therapies
Monoclonal antibodies
Pharmaceutical
innovation
Incremental
innovation
Increased survival
e.g. gastric cancer
The earlier detection and
diagnosis of cancer has
also contributed to
increased survival in
patients with cancer
Mortality is
decreasing across
a range of cancers
despite the
increasing
incidence of
disease
New therapeutic
targets
e.g. anti-angiogenic
However, cancer remains one of the leading causes of death in Latinoamerica and
survival is varied across different cancer sites; there remains a significant need for
innovation in the treatment of this disease
35
Pharmaceutical innovation provides patient benefits and are having a
significant impact on public health in the world
Prevention of illness
Reduced disease
progression and diseaserelated events
Inhibition and reversal of
disease-related damage
Pharmaceutical
innovation
Increased therapeutic
options
Improved public
health and
increased life
expectancy
Reduced adverse events
Social benefits and
improved quality of life
Increased survival
Continued pharmaceutical innovation is vital for the continued improvement of
public health
Conclusions
• Gastric cancer is one of the most common cancers in LA (within
the first five neoplasms)
• The patients are diagnosed in advanced stages, in Mexico 60% of
the patients are diagnosed in stage IV
• The perspective of lifetime is short
• With the new systemic therapy improves survival and increases
the quality of life
• It is required a comprehensive programme of prevention, early
detection and access to innovative new therapies
36