Active Ingredient: Pralsetinib
Pralsetinib is indicated as monotherapy for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 400 milligrams pralsetinib, once daily.
The recommended dose is 400 mg pralsetinib once daily on an empty stomach. Treatment should be continued until disease progression or unacceptable toxicity.
If vomiting occurs after taking a dose of pralsetinib, the patient should not take an additional dose but continue with the next scheduled dose.
If a dose of pralsetinib is missed, the patient should make up for the missed dose as soon as possible on the same day. The regular daily dose schedule for pralsetinib should be resumed the next day.
Interruption of treatment with or without dose reduction may be considered to manage adverse reactions based on severity and clinical presentation.
Patients may have their dose reduced by 100 mg decrements to a minimum dose of 100 mg once daily. Pralsetinib should be permanently discontinued in patients who are unable to tolerate 100 mg orally once daily.
Recommended dose modifications for adverse reactions are indicated in Table 1.
Table 1. Recommended dose modifications for pralsetinib for adverse reactions:
| Adverse reaction | Severitya | Dose modification |
|---|---|---|
| Pneumonitis/Interstitial lung disease (ILD) | Grade 1 or 2 | Interrupt treatment with pralsetinib until resolution. Resume at a reduced dose. Permanently discontinue pralsetinib for recurrent pneumonitis/ILD. |
| Grade 3 or 4 | Permanently discontinue for pneumonitis/ILD. | |
| Hypertension | Grade 3 | Interrupt treatment with pralsetinib for Grade 3 hypertension that persists despite optimal antihypertensive therapy. Resume at a reduced dose when hypertension is controlled. |
| Grade 4 | Permanently discontinue pralsetinib. | |
| Transaminase elevations | Grade 3 or 4 | Interrupt treatment with pralsetinib and monitor aspartate aminotransferase (AST) and alanine aminotransferase (ALT) once weekly until resolution to Grade 1 or baseline. Resume at a reduced dose. If the transaminase elevation recurs at Grade 3 or higher, permanently discontinue treatment with pralsetinib. |
| Haemorrhagic events | Grade 3 or 4 | Interrupt treatment with pralsetinib until resolution to Grade 1. Resume at a reduced dose. Permanently discontinue pralsetinib for life-threatening or recurrent severe haemorrhagic events. |
| QT prolongation | Grade 3 | Interrupt treatment with pralsetinib for QTc intervals >500 ms until QTc interval returns to <470 ms. Resume at the same dose if risk factors that cause QT prolongation are identified and corrected. Resume treatment at a reduced dose if other risk factors that cause QT prolongation are not identified. |
| Grade 4 | Permanently discontinue pralsetinib if the patient has life-threatening arrhythmia. | |
| Other clinically significant adverse reactions | Grade 3 or 4 | Interrupt treatment with pralsetinib until improvement to ≤Grade 2. Resume at a reduced dose. Permanently discontinue for recurrent Grade 4 adverse reactions. |
a Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03
Concomitant use of pralsetinib with known strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors should be avoided. If co-administration with a strong CYP3A4 inhibitor or combined P-gp and strong CYP3A4 inhibitor cannot be avoided, the current dose of pralsetinib should be reduced as recommended in Table 2. After the strong CYP3A4 inhibitor or combined P-gp and strong CYP3A4 inhibitor have been discontinued for 3 to 5 elimination half-lives, the pralsetinib dose that was taken prior to the use of the inhibitor should be resumed.
Table 2. Recommended dose modifications for pralsetinib for co-administration with strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors:
| Current pralsetinib dose | Recommended pralsetinib dose |
|---|---|
| 400 mg orally once daily | 200 mg orally once daily |
| 300 mg orally once daily | 200 mg orally once daily |
| 200 mg orally once daily | 100 mg orally once daily |
Concomitant use of pralsetinib with strong CYP3A4 inducers should be avoided. If concomitant use with a strong CYP3A4 inducer cannot be avoided, the dose of pralsetinib should be increased to double the current pralsetinib dose starting on Day 7 of co-administration of pralsetinib with the strong CYP3A4 inducer. After the strong CYP3A4 inducer has been discontinued for at least 14 days, the pralsetinib dose that was taken prior to the use of the inducer should be resumed.
Pralsetinib is for oral use. Patients should swallow the hard capsules whole with a glass of water, on an empty stomach. They should not eat for at least two hours before and at least one hour after taking pralsetinib.
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