1. Dr. Marco Matos
JOURNAL CLUB GCUH 4/07/14

2. Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting
Colorectal cancer subtyping consortium (CRCSC) identifies consensus molecular subtypes
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

3. Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting
Slide 3
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

4. Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting
CRC subtypes
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

5. Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting
How many CRC subtypes?
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

6. Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting
Population
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

7. Population

8. How to define a Consensus Molecular Subtype (CMS)?
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

9. Results - network of subtypes
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

10. Results - network of samples
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

11. Results - network of samples
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

12. Results – distribution of subtypes
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

13. Results – clinical correlates

14. Results – clinical and molecular correlates
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

15. Results – molecular correlates
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

16. Results – mutation profile (n=2,386)
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

17. Results – reverse phase protein arrays (n=439)
Presented By Rodrigo Dienstmann at 2014 ASCO Annual Meeting

18. Results – pathway analysis (n=3,891)

19. Summary – clinical and molecular correlates

20. Slide 22

21. Slide 23

22. Slide 24

23. Current markers
1: RAS MUTATIONS as exclusion for anti EGFR therapy in metastatic colorectal cancer
2: MICROSATELLITE INSTABILITY MSI as a good prognostic factor for stage II colorectal cancer

24. Presented By Sabine Tejpar at 2014 ASCO Annual Meeting
RAS mutations as exclusion for anti EGFR therapy in metastatic CRC<br /><br />
Presented By Sabine Tejpar at 2014 ASCO Annual Meeting

25. Evidence gathered over many trials

26. Presented By Sabine Tejpar at 2014 ASCO Annual Meeting
Slide 6
Presented By Sabine Tejpar at 2014 ASCO Annual Meeting

27. Presented By Sabine Tejpar at 2014 ASCO Annual Meeting
Slide 8
Presented By Sabine Tejpar at 2014 ASCO Annual Meeting

28. Presented By Sabine Tejpar at 2014 ASCO Annual Meeting
Slide 9
Presented By Sabine Tejpar at 2014 ASCO Annual Meeting

29. Colorectal cancer: from one disease to hetereogenous entities

30. Mutation frequencies in human CRC
Presented By Sabine Tejpar at 2014 ASCO Annual Meeting

31. Presented By Sabine Tejpar at 2014 ASCO Annual Meeting
Slide 16
Presented By Sabine Tejpar at 2014 ASCO Annual Meeting

32. Slide 21

33. Presented By Sabine Tejpar at 2014 ASCO Annual Meeting
Slide 27
Presented By Sabine Tejpar at 2014 ASCO Annual Meeting

34. Presented By Sabine Tejpar at 2014 ASCO Annual Meeting
<br />
Presented By Sabine Tejpar at 2014 ASCO Annual Meeting

35. Presented By Alan Venook at 2014 ASCO Annual Meeting
<br />CALGB/SWOG 80405: Phase III trial of FOLFIRI or FOLFOX with Bevacizumab or Cetuximab for patients w/ KRAS wild type untreated metastatic adenocarcinoma of the colon or rectum <br />
Presented By Alan Venook at 2014 ASCO Annual Meeting

36. Presented By Alan Venook at 2014 ASCO Annual Meeting
Slide 2
Presented By Alan Venook at 2014 ASCO Annual Meeting

37. CALGB/SWOG 80405: <br /> FINAL DESIGN

38. CRC in 2014. Is there an optimal first line treatment
FOLFOX / FOLFIRI different toxicity profile but similar efficacy
Evidence for Avastin ,VEGF inhibition in first line
Cetuximab in the second or third line
Overall survival 20 – 22 months

39. CALGB / SWOG 80405: <br /> WHY DID IT TAKE TEN YEARS?
Presented By Alan Venook at 2014 ASCO Annual Meeting

40. CALGB/SWOG 80405: Eligibility Criteria
Presented By Alan Venook at 2014 ASCO Annual Meeting

41. CALGB/SWOG 80405: Endpoints
Presented By Alan Venook at 2014 ASCO Annual Meeting

42. CALGB/SWOG 80405: Statistics
Presented By Alan Venook at 2014 ASCO Annual Meeting

43. Presented By Alan Venook at 2014 ASCO Annual Meeting
Slide 11
Presented By Alan Venook at 2014 ASCO Annual Meeting

44. CALGB/SWOG 80405: Overall Survival <br />

45. CALGB/SWOG 80405: Progression-Free Survival<br />(Investigator Determined)

46. Treatment arms - Chemotherapy
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

47. Treatment arms – Biologics with oxaliplatin
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

48. Treatment arms – Biologics with irinotecan
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

49. Results – Efficacy

50. Presented By Josep Tabernero at 2014 ASCO Annual Meeting
Results – Efficacy
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

51. Presented By Josep Tabernero at 2014 ASCO Annual Meeting
Results – Safety
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

52. Results – QoL & discontinuation reasons
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

53. Comparability with other studies
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

54. Comparability with other studies

55. CALGB 80405 and FIRE-3 <br />Are they comparable?

56. FIRE-3 – Results (KRAS ex 2 wt)

57. Presented By Josep Tabernero at 2014 ASCO Annual Meeting
Assessing response
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

58. Potential impact in survival
Presented By Josep Tabernero at 2014 ASCO Annual Meeting

59. Could expanded RAS analysis change the results?

60. Could expanded RAS analysis change the results?

61. Could expanded RAS analysis change the results?

62. CONCLUSIONS
1: Overall survival is not different between Chemo + avastin or chemo + cetuximab in first line treatment for wild type Kras CRC
2: FOLFIRI or FOLFOX in combination with Cetuximab or avatin are good options for first line treatment of wild type K ras CRC
3: OS is over 29 months
4: Results are different from FIRE
5: About 10% of patients will live more than 5 years

63. Presented By Alan Venook at 2014 ASCO Annual Meeting
Slide 30
Presented By Alan Venook at 2014 ASCO Annual Meeting