1. CRC-TREATMENT BEYOND SECOND LINE
DR DİLEK ERDEM

3. Limited stage IV disease is sometimes curable
Biological agents improve outcomes
Molecular predictive factors presented individulized treatment

4. SURVIVAL ACCORDING TO MOLECULAR SUBTYPE

5. INDIVIDUALIZED THERAPY

7. mOS INCREASES with TREATMENT LINES

8. TREATMENT DECISION CHARACTERISTICS

9. THE BEST CHOICE in RAS MUTANT 1st LINE?

10. 1st LINE RAS WT-TUMOR LOCATION

11. EGFR/VEGF? 1st LINE RAS WT

17. FACTORS AFFECT SECOND LINE TREATMENT
First line treatment is important, combination with VEGFR/+EGFR inhibitör??
Progression after 6 months of Anti-VEGFR?
Progression during 6 months of Anti-VEGFR?
Tumor molecular characteristics (MSI, B-RAF, Her-2…)
Toxicity consideration

18. VEGF INHIBITION AFTER 1st LINE BEVACIZUMAB

24. SECOND LINE

25. THIRD LINE and BEYOND

27. REGORAFENİB

30. CORRECT TRIAL

31. REGORAFENIB-TOXICITY-TIME INTERVAL

32. ReDOS:DOSE OPTIMISATION

33. TAS-102

39. B-RAF MUTANT DISEASE

40. FIRST LINE/B-RAF INHIBITION

44. mOS in B-RAF MUTANT DISEASE

45. B-RAF V600E MUTATION

47. ENCORAFENİB/ALPELİSİB/CETUXİMAB

48. ANTI-EGFR THERAPY AS A TARGET IN RAS WT/B-RAF MUTANT DISEASE

49. SWOG 1406

51. NON-V600E MUTATIONS Codon 594/596 kinase activity impaired
Favourable prognosis
L sided
Male>Female
Low grade
K-RAS mutation + MSI –
No peritoneal disease
Codon 601/597 similar to V600E

52. 2 % of CRC patients who undergo liver resection have BRAF (V600E)

53. B-RAF RESISTANCE MECHANISM

54. B-RAF MUTANT CRC
B-RAF mutant-poor prognosis/need intensive therapy (FOLFOXİRİ)
B-RAF (V600E)+MSI-H/dMMR Checkmate142
EGFR inhbitors have importance
VEGF inhbitors MAY have importance
EGFR, B-RAF ve MEK inhbitor combination
Randomised trials are on the way: Better MAPK supression (ERK inhb), B-RAF +immunotherapy, New agents:HMG-CoA redüktaz
Firstly think clinical trial
1st line FOLFOXİRİ
Anti-PD-1 in MSI-H

55. HER-2 PATHWAY

56. HER-2 POSITIVITY IS A NEGATIVE PREDICTIVE FACTOR

57. HERACLES TRIAL

58. DUAL INHIBITION

59. EGFR RESISTANCE SECONDARY TO HER-2 OVEREXPRESSION

60. MSI-H TUMOR

69. IMBLAZE TRIAL

80. TAKE HOME MESSAGES New data is coming for new biomarkers
To individualize therapy we have to choose the best options
Combination therapies better but what about the toxicity
Worse genomic alterations should be found out like B-RAF, Her-2, MSI

81. THANK YOU