Medical Pharmacology Practice Questions: Protein Tyrosine Kinase Inhibitors of EGFR: Osimertinib (Tagrisso)
Click on the correct answer.
Most tumors with activating EGFR mutations initially respond to which one(s) of the following kinase inhibitors:
Gefitinib
Erlotinib
Afatinib
A & B
B & C
A & C
A, B & C
With tumor progression in the presence and EGFR mutation, a second EGFR mutation ( referred to as EGFR gatekeeper residue (T790M)) that prevents first and second generation EGFR kinase inhibitors from binding.
True
False
Osimertinib (Tagrisso):
Orally bioavailable
Irreversible T790M-mutant EGFR inhibitor
Both
Neither
Osimertinib:
Up to 30% of untreated patients may exhibit the T790M mutation, a target for osimertinib.
Osimertinib binds to certain mutant forms of EGFR e.g. T790M, L858R) more selectively than it does to the wild-type.
Both
Neither
Osimertinib pharmacokinetics/pharmacodynamics:
Steady-state volume of distribution is about 1000 L
Bioavailability may be increased by about 20% as result of the high calorie, high fat meal.
Half-life of elimination is approximately two days.
A & B
B & C
A & C
A, B & C
Osimertinib metabolism:
Osimertinib is mainly metabolized by the liver utilizing the cytochrome P450 liver drug metabolizing system, mainly utilizing the CYP3A isoform class.
Metabolism in the liver proceeds both by oxidation and dealkylation.
Both
Neither
Osimertinib is mainly excreted in the urine (greater than 75%)
True
False
Osimertinib clinical use(s):
For first-line treatment of metastatic non-small cell lung cancer (NSCLC) exhibiting tumors with EGFR exon 19 deletions or exon 21 L858R mutations.
For treatment of metastatic EGFR T790M mutation-positive NSCLC in those patients with disease progression on or after other EGFR tyrosine kinase inhibitor treatment.
Both
Either
The most frequently observed adverse effect associated with osimertinib administration include diarrhea and skin rash.
True
False
Given that us a merit tib used during pregnancy may cause fetal harm, females of reproductive potential should employ effective contraception both during therapy and for six weeks following the last osimertinib dose.
