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Cáncer de Colon

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Presentación realizada por la Dra. Pilar Escudero del HCU Lozano Blesa, en el marco de la I Jornada de actualización e innovación en Oncología que tuvo lugar en el CIBA en enero de 2015.

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Cáncer de Colon

  1. 1. I JORNADA DE ACTUALIZACIÓN E INNOVACIÓN EN ONCOLOGÍA • CANCER DE COLON Pilar Escudero HCU Lozano Blesa Zaragoza, 20 de Enero 2015
  2. 2. Colorectal Cancer Epidemiology & Treatment Flow Cueto C. et al. Journal of American colleage of surgery. Inpress 31-May-2011 SurgerySurgery SurgerySurgery Adjuvant Chemotherapy 65% Cured Stage I Stage IIa Stage IIb Stage III Stage IV 15% 10% 35% 25%15% progresions Metastatic Treated 1L Treated 2L Treated 3L 91% 53% 34% BSC
  3. 3. Advances in the treatment of Stage IV CRC 1980 1985 1990 1995 2000 2005 2010 2015 + BSC 5-FU Irinotecan Capecitabina Oxaliplatino Cetuximab Bevacizumab Regorafenib Aflibercept Panitumumab Survival benefit from 6 months to 24-30 months Braun MS, et al. Ther Adv Med Oncol. 2011;3:43-52.
  4. 4. mCRC Heterogeneous disease Elevada heterogeneidad: Primario vs metástasis Entre las diferentes metástasis En las localizaciones metastásicas Gerlinger M, et al. N Engl J Med. 2012;366:883-892.
  5. 5. Diferencias entre colon derecho e izquierdo Missiaglia E, et al. Proximal and distal colon tumors are distint biological entities and have different prognosis. ASCO 2013 (Abst. 3526).
  6. 6. Diferencias en la sensibilidad a cetuximab entre colon derecho e izquierdo Brule Y et al. Location of colon cancer (right-sided [RC] versus left-sided [LC]) as a predictor of benefit from cetuximab (CET): NCIC CTG CO.17. J Clin Oncol 31, 2013 (suppl; abstr 3528).
  7. 7. DECISIÓN DEL TRATAMIENTO: •FACTORES •OBJETIVOS
  8. 8. Factores/Objetivos
  9. 9. Extensión de la enfermedad/Resecabilidad Nordlinger et al, Ann Oncol 2009.
  10. 10. • Elección de quimioterapia: • Tipo: • FOLFOX = FOLFIRI. • XELOX = FOLFOX. • XELIRI (posiblemente más tóxico). • Contraindicaciones y tratamientos previos. • La mayoría de los pacientes tolera un doblete de quimioterapia • Quimioterapia más biológicos mejora los resultados: • Anti-EGFR (cetuximab, panitumumab) • Antiangiogénicos (bevacizumab, aflibercept) PARADIGMAS EN EL TRATAMIENTO
  11. 11. ENSAYOS CLÍNICOS 1ª LÍNEA
  12. 12. ENSAYOS 2ª LÍNEA
  13. 13. Group Clinical presentation Treatment goal Treatment intensity GROUP 0 Clearly R0-resectable liver and/or lung metastases Cure, decrease risk of relapse Nothing or moderate (FOLFOX) GROUP 1 Not R0-resectable liver and/or lung metastases only, may become resectable after induction CT Maximum tumor shrinkage Upfront most active combination GROUP 2 Multiple metastases/sites, with rapid progression and/or tumor-related symptoms Clinically relevant tumor shrinkage as soon as possible, control PD Upfront active combination: at least doublet GROUP 3 Multiple metastases/sites with no option for resection and/or initially asymptomatic with limited risk for rapid deterioration Prevent further progression, low toxicity Watchful waiting or sequential approach (triplet regimens only in selected patients) ESMO guidelines: Treatment goals and strategies determined by patient and tumor characteristics Schmoll H-J, et al. Ann Oncol 2012;23:2479–2516 • CT, chemotherapy • PD, progressive disease
  14. 14. Factores/Objetivos
  15. 15.  ¿CUAL ES LA MEJOR OPCIÓN EN EL PACIENTE RAS NATIVO?
  16. 16. ANTIBODY NECESSARY IN 1st LINE TRETAMENT RAS WT mCRC? BEVACIZUMAB
  17. 17. ANTIBODY NECESSARY IN 1st LINE TRETAMENT RAS WT mCRC? EGFR INHIBITORS
  18. 18. ANTIBODY NECESSARY IN 1st LINE TRETAMENT RAS WT mCRC? EGFR INHIBITORS
  19. 19. PEAK study Karthaus M, et al. EJC 2013; 49 (suppl 3):abstract 2262 (and poster); Protocol ID: 20070509; ClinicalTrials.gov identifier: NCT00819780. Metastatic CRC WT KRAS exon 2 (n = 285) 1:1 mFOLFOX6 (Q2W) + panitumumab 6 mg/kg (Q2W) mFOLFOX6 (Q2W) + bevacizumab 5 mg/kg (Q2W) • Study endpoints: PFS (1°); OS, ORR, safety, exploratory biomarker analysis • No formal hypothesis testing was planned E n d o f t r e a t m e n t S a f e t y f o l l o w u p P o s t t r e a t m e n t f o l l o w u p E n d o f s t u d y 30 days (+ 3 days) Every 3 months (±28 days) until end of study R
  20. 20. 0 20 40 60 80 100 90 70 50 30 10 PEAK study RAS analysis PFS (longer follow-up analysis) Karthaus M, et al. EJC 2013; 49 (suppl 3):abstract 2262 (and poster). WT KRAS exon 2 WT RAS Proportionevent-free(%) Proportionevent-free(%) Months Months 0 364 8 12 16 28 3220 24 40 HR* = 0.84 (95% CI, 0.64–1.11) P = 0.22 HR* = 0.66 (95% CI, 0.46–0.95) P = 0.03 0 20 40 60 80 100 90 70 50 30 10 0 324 8 12 16 20 24 28 36 40 Events n (%) Median (95% CI) months Panitumumab + mFOLFOX6 (n = 142) 100 (70) 10.9 (9.7–12.8) Bevacizumab + mFOLFOX6 (n = 143) 108 (76) 10.1 (9.0–12.0) Events n (%) Median (95% CI) months Panitumumab + mFOLFOX6 (n = 88) 57 (65) 13.0 (10.9–15.1) Bevacizumab + mFOLFOX6 (n = 82) 66 (80) 10.1 (9.0–12.7)
  21. 21. PEAK study RAS analysis OS (longer follow-up analysis) Karthaus M, et al. EJC 2013; 49 (suppl 3):abstract 2262 (and poster). WT RASWT KRAS exon 2 Months Months Proportionalive(%) Proportionalive(%) 0 20 40 60 80 100 90 70 50 30 10 0 364 8 12 16 28 3220 24 40 HR* = 0.62 (95% CI, 0.44–0.89) P = 0.01 HR* = 0.63 (95% CI, 0.39–1.02) P = 0.05 44 Events n (%) Median (95% CI) months Panitumumab + mFOLFOX6 (n = 142) 52 (37) 34.2 (26.6–NR) Bevacizumab + mFOLFOX6 (n = 143) 78 (55) 24.3 (21.0–29.2) Events n (%) Median (95% CI) months Panitumumab + mFOLFOX6 (n = 88) 30 (34) 41.3 (28.8–41.3) Bevacizumab + mFOLFOX6 (n = 82) 40 (49) 28.9 (23.9–31.3) 0 324 8 12 16 20 24 28 36 0 20 40 60 80 100 90 70 50 30 10 4440
  22. 22. FOLFIRI + Cetuximab Cetuximab: 400 mg/m2 i.v. 120 min initial dose 250 mg/m2 i.v. 60 min q1wmCRC 1st -line therapy KRAS wild-type N=592 Randomization 1:1 Heinemann et al., ASCO 2013, # 3506 Key inclusion criteria - Patients >18 years with histologically confirmed diagnosis of mCRC - ECOG PS 0-2 - Prior adjuvant chemotherapy allowed if completed > 6 months before inclusion FOLFIRI + Bevacizumab Bevacizumab: 5 mg/kg i.v. 30-90 min initial q2w FOLFIRI q2w: 5-FU: 400 mg/m2 (i.v. biolus); folinic acid: 400 mg/m2 Irinotecan: 180 mg/m2 5-FU: 2,400 mg/m2 (i.v. 46) FIRE-3: Study design Primary objective: Overall response rate (ORR) Designed to detect a difference of 12% in ORR induced by FOLFIRI + cetuximab (62%) as compared to FOLFIRI + bevacizumab (50%) 284 evaluable patients per arm needed to achieve 80% power for a one-sided Fisher‘s exact test at alpha level of 2.5 %
  23. 23. ∆ = 3,7 months
  24. 24. CALGB/SWOG 80405: <br /> FINAL DESIGN
  25. 25. Phase III 80405 Trial: First-line CT + Either Cetux or Bev in KRAS-WT mCRC (Expanded ras analyses) Lenz H et al. ESMO, 2014.
  26. 26. Phase III 80405 Trial: First-line CT + Either Cetux or Bev in KRAS-WT mCRC (Expanded ras analyses) Lenz H et al. ESMO, 2014.
  27. 27. 80405: OBJECTIVE RESPONSE RATE * N = 733 CHEMO + BEV N = 369 (%) CHEMO + CETUX N = 364 (%) ORR 57% 66% CR 3% 7.4% PR 54% 58% SD 37% 26% PD 6% 8% * INVESTIGATOR ASSESSMENT; DOCUMENTED, NOT AUDITED
  28. 28.  HAY CONSENSO EN EL MANEJO DEL CCRm ?
  29. 29. 2ª Línea1ª Línea Progresión Progresión FOLFOX FOLFIRI FOLFOX FOLFIRI Anti-EGFR Anti-VEGF 1. Tournigand J Clin Oncol 2004; 2. NCCN Guidelines. Colon Cancer Version 3.2015; 3. Van Cutsem Ann Oncol. 2014. RAS wt RAS wt
  30. 30.  CONCLUSIONES
  31. 31. HAY CONSENSO … La estrategia de tratamiento se basa en: - factores relacionados con el tumor (resecabilidad) - factores relacionados con el paciente (edad, ECOG) - objetivos que se deseen alcanzar
  32. 32. El CCR es una enfermedad muy heterogénea y subclasificaciones son necesarias. HAY CONSENSO …

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