MET.NSCLC ALK +VE EMERGING DATA 2018

1. Alk +ve
NSCLC
PRESENTED BY :
HEBAT-ALLAH MAHMOUD BAKRI
- ASSISSTANT LECTURER ONCOLOGY DEP.
- ASSUIT UNIVERSITY HOSPITAL

2. AGENDA :
 INTRODUCTION
 BIOMARKER TESTING
 MOLECULAR CLASSIFICATION OF NSCLC
 ALK – REARRANGEMENT
 ALK INHIBITORS : 1ST GENERATION - 2ND GENERATION
 MECHANISMS OF RESISTANCE AND TREATMENT
 MANAGING TOXICITY OF ALK INHIBITORS
 SUMMARY

3. Molecular Features
 The identification of mutations in lung cancer has led to the development of
molecularly targeted therapy to improve the survival of subsets of patients
with metastatic disease
 subsets of adenocarcinoma now can be defined by specific mutations in
genes encoding components of (EGFR) and downstream (MAPK) and (PI3K)
signaling pathways. These mutations may define mechanisms of drug
sensitivity and primary or acquired resistance to kinase inhibitors.
 Other genetic abnormalities include translocations involving the (ALK)-which
are sensitive to ALK inhibitors, and amplification of MET

8. HOW TO FIX THE PROBLEM ?

10. TURN TO OUR
TOPIC

11. - Most common in younger non-
smokers with adenocarcinoma,
adeno-squamous carcinoma,
and rarely SCC
- Frequency: 4% overall, 33% in
EGFR-negative never-smokers
- Testing :
1- Vysis break apart FISH (> 15%
cells with split signal in 50 nuclei
scored)
2- ALK IHC also approved
3- ALK next generation
sequencing

26. N.B :
there
was no
OS d.t
cross
over in
this
study

28. 2- CERITINIB:ZYKIDA

31. 3- Alecitinib:
ALECENSA

36. resistance to ALK inhibitors :

38. Causes :

44. 4-BRIGATINIB : ALUNBRIG

49. Lorlatinib:
Inhibits All Known Crizotinib-
Resistance Mutations, Including
ALK G1202R

52. MANAGING TOXICITY OF ALK
INHIBITORS

55. SUMMARY

60. 8TH EDITION
OF AJCC
STAGING