Active Ingredient: Osimertinib
Osimertinib is indicated in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of adult patients with advanced NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 80 milligrams osimertinib, once daily.
The recommended dose of osimertinib is 80 mg osimertinib once a day when taken with pemetrexed and platinum-based chemotherapy.
Refer to the Summary of Product Characteristics for pemetrexed and cisplatin or carboplatin for the respective dosing information.
If a dose of osimertinib is missed, the dose should be made up unless the next dose is due within 12 hours.
Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. If dose reduction is necessary, then the dose should be reduced to 40 mg taken once daily.
Dose reduction guidelines for adverse reactions toxicities are provided in th following table.
Recommended dose modifications for osimertinib:
| Target organ | Adverse reactiona | Dose modification |
|---|---|---|
| Pulmonary | ILD/Pneumonitis | Discontinue osimertinib |
| Cardiac | QTc interval greater than 500 msec on at least 2 separate ECGs | Withhold osimertinib until QTc interval is less than 481 msec or recovery to baseline if baseline QTc is greater than or equal to 481 msec, then restart at a reduced dose (40 mg) |
| QTc interval prolongation with signs/symptoms of serious arrhythmia | Permanently discontinue osimertinib | |
| Cutaneous | Stevens-Johnson Syndrome and Toxic epidermal necrolysis | Permanently discontinue osimertinib |
| Blood and lymphatic system | Aplastic anaemia | Permanently discontinue osimertinib |
| Other | Grade 3 or higher adverse reaction | Withhold osimertinib for up to 3 weeks |
| If Grade 3 or higher adverse reaction improves to Grade 0-2 after withholding of osimertinib for up to 3 weeks | Osimertinib may be restarted at the same dose (80 mg) or a lower dose (40 mg) | |
| Grade 3 or higher adverse reaction that does not improve to Grade 0-2 after withholding for up to 3 weeks | Permanently discontinue osimertinib |
a Note: The intensity of clinical adverse events graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
ECGs: Electrocardiograms; QTc: QT interval corrected for heart rate
When osimertinib is used in combination, any of the treatment components should be dose modified, as appropriate. For osimertinib dose modification instructions, see table above. The pemetrexed, cisplatin or carboplatin dose should be modified in accordance with the instructions in their respective Summary of Product Characteristics. Cisplatin and/or carboplatin should be used for up to 4 cycles.
Osimertinib can be taken with or without food at the same time each day.
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