Targeted Agents: Solid Tumors Part 1

0.0(0)
studied byStudied by 0 people
learnLearn
examPractice Test
spaced repetitionSpaced Repetition
heart puzzleMatch
flashcardsFlashcards
Card Sorting

1/28

encourage image

There's no tags or description

Looks like no tags are added yet.

Study Analytics
Name
Mastery
Learn
Test
Matching
Spaced

No study sessions yet.

29 Terms

1
New cards

What are the benefits of Molecular Tumor Boards?

a multidisciplinary team that assesses tumors mutation(s)

  • reviews and provides recommendations for molecular targeted therapies

  • track pt outcomes

2
New cards

Small molecular drugs (TKIs) vs Biologic agents (monoclonal antibodies): Route of administration

TKIs: PO

Monoclonal antibodies: IV, SubQ, IM

3
New cards

Small molecular drugs (TKIs) vs Biologic agents (monoclonal antibodies): Absorption and distribution

TKIs: through passive diffusion/permeability and active transporters

Monoclonal antibodies: through lymphatic system due to large size

4
New cards

Small molecular drugs (TKIs) vs Biologic agents (monoclonal antibodies): Target

TKIs: surface and intracellular targets - receptors + proteins

Monoclonal antibodies: membrane proteins + soluble proteins/signaling molecules

5
New cards

Small molecular drugs (TKIs) vs Biologic agents (monoclonal antibodies): Metabolism/clearance

TKIs: mainly through CYP enzymes, renal excretion, biliary excretion; usually linear

Monoclonal antibodies: through proteolysis, hydrolysis; target mediated clearance

6
New cards

Small molecular drugs (TKIs) vs Biologic agents (monoclonal antibodies): Drug interactions

TKIs: PK and PD

Monoclonal antibodies: PD

7
New cards

Name the K-RAS G12C inhibitors

  • sotorasib (Kumakras)

  • adagrasib (Krazati)

8
New cards

Class effects of K-RAS inhibitors

  • hepatotoxicity

  • pulmonary toxicity

  • decreased albumin/electrolytes

  • lymphocytopenia

  • heart failure (rare)

9
New cards

Unique effects of sotorasib (lumakras)

Decreased Hgb

10
New cards

Unique effects of Adagrasib (Krazati)

  • GI toxicity

  • QTc prolongation

  • increased CPK

  • AKI

  • mental status change (rare)

  • hyperpigmentation

11
New cards

are EGFR mutations likely to occur in the same settings as KRAS mutations

NO due to functional redundancy

12
New cards

Name the ALK rearrangement inhibitors

  • Alectinib

  • Brigatinib

  • Ceritinib

  • Crizotinib

  • Ensartinib

  • Lorlatinib

13
New cards

Class effects of ALK rearrangement inhibitors

  • bradycardia

  • pulmonary toxicity

  • hepatotoxicity (not in lorlatnib)

  • photosensivitity (not in lorlatnib)

14
New cards

Unique effects of lorlatinib

  • CNS effects

  • Hyperlipidemia

15
New cards

Dose modification and medical management for lorlatinib: CNS effects

grading

  • grade 1: continue at the same sode or withhold until recovery to baseline. Resume at the same or reduced dose

  • grade 2-3: withhold dose until Grade 0-1. Resume at a reduced dose

  • Grade 4: D/C

medical management

  • psych consult

  • antipsychotic agents

  • antidepressants agents

  • agents for sleep

16
New cards

Dose modification and medical management for lorlatinib: Hypercholesterolemia or hypertriglyceridemia

grading

  • grade 4: withhold until recovery to less than or equal to grade 2. resume at the dose. If severe or recurraence, resume at reduced dose

medical management

  • Statins (DDI with lorlatinib): ROSUVASTATIN PREFERRED

  • fibrates (2nd line)

17
New cards

Dose modification and medical management for lorlatinib: HTN

grading

  • grade 3: withhold until recovery to grade 0-1,t hen resume at same dose. If adequate control cannot be achieved with medical management, D/C

  • grade 4: withhold until recovery to less than or equal to grade 0-1 and resume at a reduced dose. If grade 4 reoccurs, D/C

medical management

  • CCB

  • ACE-I/ARB

  • thiazide diuretics

18
New cards

Dose modification and medical management for lorlatinib: Hyperglycemia

grading

  • grade 4: withhold until adequatelly controlled, then resume at the next lower dosage. If controlled cannot be achieved, D/C

medical management

  • oral agents

  • injectable agents

  • insulin

19
New cards

Name the MET exon skipping mutation inhibitors

  • capmatinib (tabcrecta)

  • crizotinib (Xalkori)

  • tepotinib (tepmetko)

20
New cards

Class effects of MET inhibitors

  • hepatoxicity

  • pulmonary toxicity

  • peripheral edema

  • decreased hemoglobin/lymphocytopenia

21
New cards

Unique effects of capmatinib (tabcrecta)

edema

  • facial, genital

pancreatic toxicity

22
New cards

Unique effects of tepotinib (tepmetko)

pulmonary embolism (RARE)

23
New cards

Name the RET rearrangement inhibitors

  • Cabozantinib

  • Pralsetinib

  • Selpercatinib

24
New cards

Class effects of RET inhibitors

  • hemorrhage

  • hepatotoxicity

  • HTN

  • wound healing impairment

  • pulmonary toxicity (except carbozantinib)

  • tumor lysis syndrome (except in carbozantinib)

  • thyroid dysfunction (except in pralsetinib)

25
New cards

Which of the following agents should you monitor for QTc prolongations?

  • adagradisb

  • selpercatinib

  • crizotinib

  • ceritinib

26
New cards

Which agents are CYP3A4 inhibitors

  • adagrasib

  • crizotinib

  • ceritinib

  • lorlatinib

27
New cards

Which agents are CYP3A4 substrates

All of them

28
New cards

Which of the K-RAS inhibitors is most likely to prolong the QTc interval?

Adagrasib (Krazati)

29
New cards

What questions would you ask of a patient receiving Sotorasib or Adagrasib to probe for the onset of delayed toxicities?

  • What lab tests would you follow to monitor for toxicities?

  • Does better CNS penetration by Adagrasib mean that Sotorasib is not effective upon CNS metastases of cancers?

Tests

  • Imaging can tell us if its malignant-caused or if its true ADR caused by the medication through inflammation

  • LFTs

  • CBC

CNS pentration

  • sotorasib still have good activity within the CNS