Active Ingredient: Tislelizumab
Tislelizumab in combination with pemetrexed and platinum-containing chemotherapy is indicated for the first-line treatment of adult patients with non-squamous non-small cell lung cancer whose tumours have PD-L1 expression on ≥50% of tumour cells with no EGFR or ALK positive mutations and who have:
Tislelizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel is indicated for the first-line treatment of adult patients with squamous non-small cell lung cancer who have:
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 200 milligrams tislelizumab, once every 3 weeks.
The recommended dose of tislelizumab is 200 mg administered by intravenous infusion once every 3 weeks, in combination with chemotherapy.
When tislelizumab and chemotherapy are administered on the same day, tislelizumab should be administered before chemotherapy. The Summary of Product Characteristics (SmPC) for the chemotherapy product should be referred to for dosing as well as for recommendations on corticosteroid use as premedication for the prevention of chemotherapy-related adverse reactions.
Patients should be treated with tislelizumab until disease progression or unacceptable toxicity.
No dose reductions of tislelizumab in combination therapy are recommended. Tislelizumab should be withheld or discontinued as described in Table 1.
Table 1. Recommended treatment modifications for tislelizumab:
| Immune-related adverse reaction | Severity1 | Tislelizumab treatment modification |
|---|---|---|
| Pneumonitis | Grade 2 | Withhold2,3 |
| Recurrent grade 2; grade 3 or 4 | Permanently discontinue3 | |
| Hepatitis | ALT or AST >3 to 8 x ULN or total bilirubin >1.5 to 3 x ULN | Withhold2,3 |
| ALT or AST >8 x ULN or total bilirubin >3 x ULN | Permanently discontinue3 | |
| Rash | Grade 3 | Withhold2,3 |
| Grade 4 | Permanently discontinue3 | |
| Severe cutaneous adverse reactions (SCARs) | Suspected SCARs, including SJS or TEN | Withhold2,3 For suspected SJS or TEN, do not resume unless SJS/TEN has been ruled out in consultation with appropriate specialist(s). |
| Confirmed SCARs, including SJS or TEN | Permanently discontinue | |
| Colitis | Grade 2 or 3 | Withold2,3 |
| Recurrent grade 3; grade 4 | Permanently discontinue3 | |
| Myositis/rhabdomyolysis | Grade 2 or 3 | Withhold2,3 |
| Recurrent grade 3; grade 4 | Permanently discontinue3 | |
| Hypothyroidism | Grade 2, 3 or 4 | Hypothyroidism may be managed with replacement therapy without treatment interruption. |
| Hyperthyroidism | Grade 3 or 4 | Withhold2 For grade 3 or 4 that has improved to grade ≤2 and is controlled with anti-thyroid therapy, if indicated continuation of tislelizumab may be considered after corticosteroid taper. Otherwise, treatment should be discontinued. |
| Adrenal insufficiency | Grade 2 | Consider withholding treatment until controlled by HRT. |
| Grade 3 or 4 | Withhold3 For grade 3 or 4 that has improved to grade ≤2 and is controlled with HRT, if indicated continuation of tislelizumab may be considered after corticosteroid taper. Otherwise, treatment should be discontinued.3 | |
| Hypophysitis | Grade 2 | Consider withholding treatment until controlled by HRT. |
| Grade 3 or 4 | Withhold2,3 For grade 3 or 4 that has improved to grade ≤2 and is controlled with HRT, if indicated continuation of tislelizumab may be considered after corticosteroid taper. Otherwise, treatment should be discontinued.3 | |
| Type 1 diabetes mellitus | Type 1 diabetes mellitus associated with grade ≥3 hyperglycaemia (glucose >250 mg/dl or >13.9 mmol/l) or associated with ketoacidosis | Withhold For grade 3 or 4 that has improved to grade ≤2 with insulin therapy, if indicated continuation of tislelizumab may be considered once metabolic control is achieved. Otherwise, treatment should be discontinued. |
| Nephritis with renal dysfunction | Grade 2 (creatinine >1.5 to 3 x baseline or >1.5 to 3 x ULN) | Withhold2,3 |
| Grade 3 (creatinine >3 x baseline or >3 to 6 x ULN) or grade 4 (creatinine >6 x ULN) | Permanently discontinue3 | |
| Myocarditis | Grade 2, 3 or 4 | Permanently discontinue3 |
| Neurological toxicities | Grade 2 | Withhold2,3 |
| Grade 3 or 4 | Permanently discontinue3 | |
| Pancreatitis | Grade 3 pancreatitis or grade 3 or 4 serum amylase or lipase levels increased (>2 x ULN) | Withhold2,3 |
| Grade 4 | Permanently discontinue3 | |
| Other immune-related adverse reactions | Grade 3 | Withhold2,3 |
| Recurrent grade 3; grade 4 | Permanently discontinue3 | |
| Infusion-related reactions | Grade 1 | Consider pre-medication for prophylaxis of subsequent infusion reactions. Slow the rate of infusion by 50%. |
| Grade 2 | Interrupt infusion. Resume infusion if resolved or decreased to grade 1, and slow rate of infusion by 50%. | |
| Grade 3 or 4 | Permanently discontinue |
ALT = alanine aminotransferase, AST = aspartate aminotransferase, HRT = hormone replacement therapy, SJS = Stevens-Johnson syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal
1 Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0). Hypophysitis grade is in accordance with NCI-CTCAE v5.0.
2 Resume in patients with complete or partial resolution (grade 0 to 1) after corticosteroid taper over at least 1 month. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or inability to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids.
3 Initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper to ≤10 mg/day (or equivalent) over at least 1 month is recommended, except for pneumonitis, where initial dose of 2 to 4 mg/kg/day is recommended.
It is to be administered as an infusion and must not be administered as an intravenous push or single bolus injection.
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