Active Ingredient: Avapritinib
Avapritinib is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 300 milligrams avapritinib, once daily.
For GIST, the recommended starting dose of avapritinib is 300 mg orally once daily, on an empty stomach. Treatment should be continued until disease progression or unacceptable toxicity occurs.
Patient selection for treatment of unresectable or metastatic GIST harbouring the PDGFRA D842V mutation should be based on a validated test method.
Concomitant use of avapritinib with strong or moderate CYP3A inhibitors should be avoided. If concomitant use with a moderate CYP3A inhibitor cannot be avoided, the starting dose of avapritinib must be reduced from 300 mg to 100 mg orally once daily.
If a dose of avapritinib is missed, the patient should make up for the missed dose unless the next scheduled dose is within 8 hours. If the dose has not been taken at least 8 hours prior to the next dose, then that dose must be omitted and the patient should resume treatment with the next scheduled dose.
If vomiting occurs after taking a dose of avapritinib, the patient must not take an additional dose but continue with the next scheduled dose.
Irrespective of indication, interruption of treatment with or without dose reduction may be considered to manage adverse reactions based on severity and clinical presentation.
The dose should be adjusted as recommended, based on safety and tolerability.
Dose reductions and modifications for adverse reactions are provided in Tables 1 and 2.
Table 1. Recommended dose reductions for avapritinib for adverse reactions:
| Dose reduction | GIST (starting dose 300 mg) |
|---|---|
| First | 200 mg once daily |
| Second | 100 mg once daily |
Table 2. Recommended dose modifications for avapritinib for adverse reactions:
| Adverse reaction | Severity* | Dose modification |
|---|---|---|
| Intracranial haemorrhage | All Grades | Permanently discontinue avapritinib. |
| Cognitive effects** | Grade 1 | Continue at the same dose, reduce dose or interrupt until improvement to baseline or resolution. Resume at the same dose or at a reduced dose. |
| Grade 2 or Grade 3 | Interrupt therapy until improved to baseline, Grade 1, or resolution. Resume at the same dose or at a reduced dose. | |
| Grade 4 | Permanently discontinue avapritinib. | |
| Other adverse reactions | Grade 3 or Grade 4 | Interrupt therapy until less than or equal to Grade 2. Resume at the same dose or at a reduced dose, if warranted. |
* The severity of adverse reactions graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and 5.0
** Adverse reactions with impact on Activities of Daily Living (ADLs) for Grade 2 or higher adverse reactions
The avapritinib tablets must be taken on an empty stomach at least 1 hour before or at least 2 hours after a meal.
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