Recommended treatment modifications for Keytruda (pembrolizumab)1
|Immune-related adverse reactions||Severity||Treatment modification|
|Pneumonitis||Grade 2||Withhold until adverse event recovers to Grade 0-1*|
|Grade 3 or 4, or recurrent Grade 2||Permanently discontinue|
|Colitis||Grade 2 or 3||Withhold until adverse event recovers to Grade 0-1*|
|Grade 4 or recurrent grade 3||Permanently discontinue|
|Nephritis||Grade 2 with creatinine >1.5 to ≤3 times upper limit of normal (ULN)||Withhold until adverse event recovers to Grade 0-1*|
|Grade ≥ 3 with creatinine > 3 times ULN||Permanently discontinue|
Grade 2 adrenal insufficiency and hypophysitis
|Withhold treatment until controlled by hormone replacement|
|Grades 3 or 4 adrenal insufficiency or symptomatic hypophysitis||Withhold until adverse reactions recover to Grades 0 1*|
|Type 1 diabetes associated with Grade ≥ 3 hyperglycaemia (glucose > 250 mg/dL or > 13.9 mmol/L) or associated with ketoacidosis|
Hyperthyroidism Grade ≥ 3
|For patients with Grade 3 or Grade 4 endocrinopathies that improved to Grade 2 or lower and are controlled with hormone replacement, if indicated, continuation of pembrolizumab may be considered after corticosteroid taper, if needed. Otherwise treatment should be discontinued.|
|Hypothyroidism||Hypothyroidism may be managed with replacement therapy without treatment interruption.|
NOTE: for RCC patients treated with pembrolizumab in combination with axitinib with liver enzyme elevations, see dosing guidelines following this table.
|Grade 2 with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 to 5 times ULN or total bilirubin >1.5 to 3 times ULN||Withhold until adverse reactions recovers to Grade 0-1*|
|Grade ≥3 with AST or ALT >5 times ULN or total bilirubin >3 times ULN||Permanently discontinue|
|In case of liver metastasis with baseline Grade 2 elevation of AST or ALT, hepatitis with AST or ALT increases ≥50% and lasts ≥1 week||Permanently discontinue|
|Skin reactions||Grade 3 or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)||Withhold until adverse reactions recovers to Grade 0-1*|
|Grade 4 or confirmed SJS or TEN||Permanently discontinue|
|Other immune-related adverse reactions||Based on severity and type of reaction (Grade 2 or Grade 3)|
Grade 3 or 4 myocarditis
Grade 3 or 4 encephalitis
Grade 3 or 4 Guillain-Barré
Grade 4 or recurrent Grade 3
|Withhold until adverse reactions recover to Grade 0-1*|
|Infusion-related reactions||Grade 3 or 4||Permanently discontinue|
Note: toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4). * If treatment-related toxicity does not resolve to Grade 0-1 within 12 weeks after last dose of KEYTRUDA, or if corticosteroid dosing cannot be reduced to ≤10mg prednisone or equivalent per day within 12 weeks, KEYTRUDA should be permanently discontinued.
The safety of re-initiating pembrolizumab therapy in patients previously experiencing immune-related myocarditis is not known.1
KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued for Grade 4 or recurrent Grade 3 immune-related adverse reactions, unless otherwise specified in table above. 1
For Grade 4 haematological toxicity, only in patients with cHL, KEYTRUDA should be withheld until adverse reactions recover to Grades 0- 1. 1
KEYTRUDA in combination with axitinib in RCC1
For RCC patients treated with KEYTRUDA in combination with axitinib, see the Summary of Product Characteristics (SmPC) regarding dosing of axitinib. When used in combination with pembrolizumab, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer.
For liver enzyme elevations, in patients with RCC being treated with KEYTRUDA in combination with axitinib:
•If ALT or AST ≥ 3 times ULN but < 10 times ULN without concurrent total bilirubin ≥ 2 times ULN, both KEYTRUDA and axitinib should be withheld until these adverse reactions recover to Grades 0-1. Corticosteroid therapy may be considered. Rechallenge with a single medicine or sequential rechallenge with both medicines after recovery may be considered. If rechallenging with axitinib, dose reduction as per the axitinib SmPC may be considered.
•If ALT or AST ≥ 10 times ULN or > 3 times ULN with concurrent total bilirubin ≥ 2 times ULN, both KEYTRUDA and axitinib should be permanently discontinued and corticosteroid therapy may be considered.
KEYTRUDA in combination with lenvatinib1
When used in combination with lenvatinib, one or both medicines should be interrupted as appropriate. Lenvatinib should be withheld, dose reduced, or discontinued in accordance with the instructions in the lenvatinib SmPC for combination with pembrolizumab. No dose reductions are recommended for KEYTRUDA.
Patients treated with KEYTRUDA must be given the patient alert card and be informed about the risks of KEYTRUDA.1
Please refer to the SmPC for further information on both adverse events and immune related adverse events.