Active Ingredient: Dostarlimab
Dostarlimab is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer (EC) that has progressed on or following prior treatment with a platinum-containing regimen.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 500 milligrams dostarlimab, once every 3 weeks, 4 doses in total, over the duration of 15 weeks. Afterwards, intravenous, 1,000 milligrams dostarlimab, once every 6 weeks.
The recommended dose as monotherapy is 500 mg dostarlimab every 3 weeks for 4 cycles followed by 1000 mg every 6 weeks for all cycles thereafter.
The dosage regimen is presented in table 1.
Table 1. Dosage regimen for patients treated with dostarlimab:
Administration of dostarlimab should continue according to the recommended schedule until disease progression or unacceptable toxicity.
Dose reduction is not recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability. Recommended modifications to manage adverse reactions are provided in table 2.
Detailed guidelines for the management of immune-related adverse reactions and infusion-related reactions are described in section 4.4.
Table 2. Recommended dose modifications for dostarlimab:
| Immune-related adverse reactions | Severity gradea | Dose modification |
| Colitis | 2 to 3 | Withhold dose. Restart dosing when toxicity resolves to grade 0-1. |
| 4 | Permanently discontinue. | |
| Hepatitis | Grade 2 with ASTb or ALTc >3 and up to 5 × ULNd or total bilirubin >1.5 and up to 3 × ULN | Withhold dose. Restart dosing when toxicity resolves to grade 0 to 1. |
| Grade ≥3 with AST or ALT >5 × ULN or total bilirubin >3 × ULN | Permanently discontinue (see exception below)e. | |
| Type 1 diabetes mellitus (T1DM) | 3 to 4 (hyperglycaemia) | Withhold dose. Restart dosing in appropriately managed, clinically and metabolically stable patients. |
| Hypophysitis or adrenal insufficiency | 2 to 4 | Withhold dose. Restart dosing when toxicity resolves to grade 0 to 1. Permanently discontinue for recurrence or worsening while on adequate hormonal therapy. |
| Hypothyroidism or hyperthyroidism | 3 to 4 | Withhold dose. Restart dosing when toxicity resolves to grade 0 to 1. |
| Pneumonitis | 2 | Withhold dose. Restart dosing when toxicity resolves to grade 0-1. If grade 2 recurs, permanently discontinue. |
| 3 to 4 | Permanently discontinue. | |
| Nephritis | 2 | Withhold dose. Restart dosing when toxicity resolves to grade 0-1. |
| 3 to 4 | Permanently discontinue. | |
| Immune-mediated rash | 3 | Withhold dose. Restart dosing when toxicity resolves to grade 0-1. |
| 4 | Permanently discontinue. | |
| Other immune-related adverse reactions (including but not limited to myositis, myocarditis, encephalitis, demyelinating neuropathy including Guillain Barré syndrome, sarcoidosis, autoimmune haemolytic anaemia, pancreatitis, iridocyclitis, uveitis, diabetic ketoacidosis, arthralgia, solid organ transplant rejection, graft-versus-host disease) | 3 | Withhold dose. Restart dosing when toxicity resolves to grade 0-1. |
| 4 | Permanently discontinue. | |
| Recurrence of immune-related adverse reactions after resolution to ≤ grade 1 (except for pneumonitis, see above) | 3 to 4 | Permanently discontinue. |
| Other adverse reactions | Severity gradea | Dose modification |
| Infusion-related reactions | 2 | Withhold dose. If resolved within 1 hour of stopping, may be restarted at 50% of the original infusion rate, or restart when symptoms resolve with pre-medication. If grade 2 recurs with adequate premedication, permanently discontinue. |
| 3 to 4 | Permanently discontinue. |
a Toxicity graded per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
b AST = aspartate aminotransferase
c ALT = alanine aminotransferase
d ULN = upper limit of normal
e For patients with liver metastases who begin treatment with grade 2 increase of AST or ALT, if AST or ALT increases by ≥50% relative to baseline and lasts for at least 1 week, then treatment should be discontinued.
Dostarlimab should be administered by intravenous infusion using an intravenous infusion pump over 30 minutes.
Dostarlimab must not be administered as an intravenous push or bolus injection.
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