Cómo se trata el cáncer gástrico avanzado en América Latina? Cómo podemos reducir la carga de la enfermedad?

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1 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

2 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

3 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): Diagnóstico de cáncer gástrico: CÁNCER GÁSTRICO Generalidades 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

4 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 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

5 Número de muertes (100,000) Mortalidad por Cáncer Gástrico en América Latina ( ) México Argentina Colombia Chile Peru Costa Rica PROYECCIONES DE MORTALIDAD POR CÁNCER SEGÚN ÓRGANOS LATINOAMÉRICA Y EL CARIBE SEGÚN OPS/PAHO Estómago Hígado Colon Mamas cervical año 5

6 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):

7 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): 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):

8 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 Feb; 24(2): 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):

9 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 AÑOS EN AMERICA LATINA 9

10 CANCER GASTRICO, ESTANDAR DE AÑOS DE SUPERVIVENCIA EN ADULTOS ENTRE 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 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

11 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

12 CÓMO DISMINUIR LA MORTALIDAD POR CÁNCER GÁSTRICO? (Primera causa de muerte por cáncer) Bonus Track 12

13 Cardias GE Junction Are increasing Pylorus and Antrus GC Are decreasing MINISTERIO DE SALUD. Guía Clínica CÁNCER GÁSTRICO. SANTIAGO: Minsal,

14 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

15 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

16 Age-standardised rate per 100,000 incidence and mortality 70% occur in developing countries, half in Asia (China) 16

17 5-year prevalence and incidence Ratio mortality / incidence (MI)

18 Gastric Cancer - Brazil ,000 new cases of cancer¹ (without skin non melanoma); / 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 Dec;27(6): doi:.1016/j.bpg Epub 2013 Sep 27. Cost-effectiveness of screening and treating Helicobacter pylori for gastric cancer prevention. Lansdorp-Vogelaar I1, Sharp L. 18

19 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 1 St 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$ St line lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1.0 g twice daily for 10 days² (efficacy 91.3% ITT analysis) U$ St line (retreatement) - lansoprazole 30 mg, levofloxacino 250 mg, furazolidona 200 mg twice daily for 7 days³ (89.4% PP, 87.5%in ITT); U$ 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 , Mar 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 Jan51(1): 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

20 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 , June Available from < access on 25 Aug Epub Apr 19, rd 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 , June Available from < access on 25 Aug Epub Apr 19,

21 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

22 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 ² ³ Average costs of gastric cancer patients undergoing chemotherapy (Medicare*) 1 st -line therapy treatment-related supportive care $25,000 $20,000 $15,000 $10,000 $5,000 Post 1 st -line therapy treatment-related supportive care $25,000 $20,000 $15,000 $10,000 $5,000 $0 Multiple lines of therapy 1st-line only $0 Multiple lines of therapy 1st-line only * Not including hospital admissions or clinic visits Karve et al, J Gastric Cancer

23 Gastric cancer: real world data - Brazilian health plan M/W - 2:1 32 % 68 % 1-year survival rate 57 % Year Beneficiaries Prevalence Prop. 100, , , , , ,88 Gastric cancer: real world data - Brazilian health plan Procedures Annual cost (in US $*) Visits 1,541 Exams 47,736 Hospitalizations 401,711 Others 210,810 Totals 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

24 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

25 Role of innovative therapies for the management of gastric cancer September 6, 2015 Dr. Germán Calderillo Ruiz Gastric Cancer Percentage by Stage INCAN- (Mexico) Stage n=506 (%) China (Shanghai) N=7,342 (%) Asia- Pacific n=2,075 (%) Japon N=12,644 (%) 0-I II III IV AP Corea, Malasia, Filipinas, Taiwan, Tailandia Gastric Cancer 2013 Asia Pac J Clin Oncol 2014 J Surg

26 Gastric Cancer Survival by stage IA IB IIA IIB IIIA IIIB IIIC IV J Clin Oncol 2013;31: Key advances in the development of gastric cancer therapeutics s s s 2000 s and beyond fluorouracil Metotrexate 5-fluorouracil Adriamicin Etoposide Cisplatin Trastuzumab Lapatinib 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:

27 Median overall survival, month Median overall survival, month New chemotherapy for gastric cancer can be linked to extended survival for patients 14 Incremental innovation in gastric cancer BSC- Best support care Fu -Fluorouracil I -Irinotecan D -Docetaxel C -Cisplatin E -Epirubicin O -Oxaliplatin X -Capecitabine 0 BSC Fu IF DCF CF ECF EOX Cancer 1993;72:37-41 Ann Oncol 2008;19: J Clin Oncol 2006;24: Nat Rev Clin Oncol 2014;11:10-21 N Eng J Med 2008;358:36-46 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 BSC Fu IF DCF CF ECF EOX improvement of symptoms Symptom % Reflux 60 Anorexia 65 Pain 68 Dysphagia 70 Vomiting 75 Weight loss 80 Innovation therapeutics in gastric cancer has led to improvement in survival and quality of life 27

28 molecular Advanced Gastric Cancer Innovative Therapies Overexpression of EGFR Overexpression of HER2neu Overexpression C-MET Anti-angiogenic Therapy Gastroenterology 2011;141: 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:

29 HER2 IHC staining (3+) Stomach cancer UEG INCAN-Mexico SMeO 2014 ESMO 2014 UEG (n=43) Stomach (n=168) Overall 18.6% 10.7% Men 8/37 (21.3%) 14/110 (12.7%) Women 0/6 (0%) 4/58 (6.9%) 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:

30 Median overall survival, month Chemotherapy Trial ToGA / Her 2neu (3+) Trial LOGIC/ Her 2neu (3+) 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 Incremental innovation in gastric cancer BSC EOX XP - T Pacli-L BSC- Best supportive care 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

31 Median overall survival, month Chemotherapy Trial ToGA / HER 2neu (3+) Trial LOGIC/ HER 2neu (3+) 13 months New chemotherapy for gastric cancer can be linked to extended survival for patients Incremental innovation in gastric cancer BSC EOX XP - T Pacli-L Selected population 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

32 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 < 0.05 Placebo 3.6 Irinotecan 4.0 <0.05 Placebo 2.4 Eur J Cancer 2011;47: J Clin Oncol 2012; 13:

33 Median overall survival, month P<0.05 P<0.05 P<0.05 p=0.01 P<0.05 p= months 4.5 months Gastric cancer Second line treatment with chemotherapy Adverse Factors HR p Value Activity level (ECOG) Hb < ACE > 50 ng/ml Number of metastases > 2 sites Time to progression < 6 months Br J Cancer 2008;99: Innovative developments in therapy for gastric cancer can be linked to extended survival for patients (2 nd line) Incremental innovation in gastric cancer P- paclitaxel Incremental innovation in gastric cancer has led to improvement in survival 33

34 Overall survival Overall survival Overall survival Overall survival Ramucirumab in patients with metastatic gastric cancer Impact on survival 2nd line (REGARD study) HR (IC 95%) ( ) P=0.047 Ramucirumab (n=238) Placebo (n=117) (RAINBOW study) HR (IC 95%) ( ) P= Ramucirumab +Paclitaxel (n=330) Placebo + paclitaxel (n=335) 3.8 m 5.2 m 1.4 months (37%) 9.6 m 7.4 m 2.3 months (30%) months months Fuchs ChS. Lancet 2014;383:31-39 Wilke H. Lancet Oncol 2014;15: Other innovative therapies in patients with metastatic gastric cancer impact on survival 2nd line HR (IC 95%) 0.59 ( ) P= Lapatinib-Paclitaxel (n=52) Paclitaxel (n=49) HR (IC 95%) 0.62 ( ) P= Apatinib (n=176) Placebo (n=91) Selected population HER2 (3+) 7.6 m 14.0 m Months Months Taroh S. J Clin Oncol 2014;32: ESMO

35 Innovative therapies in patients with metastatic gastric cancer impact on survival 2nd line 1st line 2nd line Gastric Cancer Stage IV N=802 N=640 (80%) Treatment with Chemotherapy +/- Innovative therapy N=240 (38%) Received treatment in 2nd line SV median 8 months (3-20) SV median 6 months (2-6) Incan - México Pharmaceutical innovation has increased the likelihood of survival for patients with cancer Novel therapies Pharmaceutical innovation Monoclonal antibodies Incremental innovation e.g. gastric cancer New therapeutic targets Increased survival 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 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

36 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 Pharmaceutical innovation Inhibition and reversal of disease-related damage Increased therapeutic options Reduced adverse events Improved public health and increased life expectancy 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