Targeted Therapies - Tyrosine Kinase Inhibitors (TKIs)

Question 1

how are TKIs administered

Answer 1

Orally administered

Question 2

Target: BCR-ABL fusion gene (AKA Philadelphia Chromosome)

Answer 2

1. Imatinib (Gleevec)*
2. Dasatinib
3. Nilotinib

Question 3

Suffix endings for TKIs

Answer 3

1. -tinib
2. -nib

Question 4

Safety concerns for BCR-ABL inhibitors (imatinib)

Answer 4

1. FLUID RETENTION*
2. QT PROLONGATION (greatest risk with nilotinib)
3. GI UPSET (imatinib must be taken WITH FOOD)

Question 5

Target: BRAF V600E or V600K mutation*

Answer 5

1. Dabrafenib
2. Vemurafenib

Question 6

BRAF safety concerns

Answer 6

1. New malignancies
2. QT prolongation

Question 7

Q: TKI: EGFR inhibitors
Q: Target
Q: safety concerns

Answer 7

1. Afatinib (Gilotrif)
   Erlotinib (Tarceva)
2. target EGFR gene MUTATION***

(note: diff from mAbs EGFR inhibitors as they target EGFR EXPRESSION*)

3. ACNEIFORM RASH* (all same safety as EGFR mAb Cetuximab)

Question 8

Q: MOA: Mitogen- Activated Extracellular Kinase (MEK) 1 and 2 inhibitors: inhibit MEK, a cell signaling protein downstream from RAF

Q: Target
Q: safety concerns

Answer 8

1. Cobimetinib
   Trametinib
2. Target BRAF V600E or V600K mutation when used in combination with a BRAF inhibitor
3. Retinopathy, Rhabdomyolysis