CRC-TREATMENT BEYOND SECOND LINE DR DİLEK ERDEM

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

SURVIVAL ACCORDING TO MOLECULAR SUBTYPE

INDIVIDUALIZED THERAPY

mOS INCREASES with TREATMENT LINES

TREATMENT DECISION CHARACTERISTICS

THE BEST CHOICE in RAS MUTANT 1st LINE?

1st LINE RAS WT-TUMOR LOCATION

EGFR/VEGF? 1st LINE RAS WT

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

VEGF INHIBITION AFTER 1st LINE BEVACIZUMAB

SECOND LINE

THIRD LINE and BEYOND

REGORAFENİB

CORRECT TRIAL

REGORAFENIB-TOXICITY-TIME INTERVAL

ReDOS:DOSE OPTIMISATION

TAS-102

B-RAF MUTANT DISEASE

FIRST LINE/B-RAF INHIBITION

mOS in B-RAF MUTANT DISEASE

B-RAF V600E MUTATION

ENCORAFENİB/ALPELİSİB/CETUXİMAB

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

SWOG 1406

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

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

B-RAF RESISTANCE MECHANISM

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

HER-2 PATHWAY

HER-2 POSITIVITY IS A NEGATIVE PREDICTIVE FACTOR

HERACLES TRIAL

DUAL INHIBITION

EGFR RESISTANCE SECONDARY TO HER-2 OVEREXPRESSION

MSI-H TUMOR

IMBLAZE TRIAL

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

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