Table 3 Dose modification recommendations for key everolimus-related adverse events
Adverse event | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
|---|---|---|---|---|
Non-infectious pneumonitis [19] | Consider a 50% decrease in everolimus dose | Consider interruption of therapy until symptoms improve to grade ≤1; re-initiate at 50% of previous dose. Discontinue if no recovery within 4 weeks | Interrupt everolimus until symptoms resolve to grade ≤1; consider re-initiating at 50% of previous dose. If toxicity recurs at grade 3, consider discontinuation | Discontinue everolimus |
Infectionsa | No change in everolimus dose | Maintain dose if tolerated; interrupt if intolerable or grade 2 recurrence until recovery to grade ≤1 then restart at same dose. | Interrupt dose until recovery to grade ≤1, then restart at reduced dose. If dose interrupted >21 days, consider discontinuation | Discontinue everolimus |
Stomatitis [19] | - | Temporary dose interruption until recovery to grade ≤1; re-initiate at same dose. If AE recurs at grade 2, interrupt dose until recovery to grade ≤1; re-initiate at 50% of previous dose | Temporary dose interruption until recovery to grade ≤1; re-initiate at 50% of previous dose | Discontinue everolimus |
Rasha | - | If toxicity tolerable, no dose adjustment required. If intolerable, temporary dose interruption until recovery to grade ≤1; re-initiate at same dose. If AE recurs at grade 2, interrupt dose until recovery to grade ≤1; re-initiate at 50% of previous dose | Temporary dose interruption until recovery to grade ≤1. Consider re-initiating at 50% of previous dose. If toxicity recurs at grade 3, consider discontinuation |  |
Metabolic events [19]  Hypercholesterolaemia  Hyperglycaemia  Hypophosphataemia  Hypertriglyceridaemia  Hyperiuricaemia | - | No dose adjustment required | Temporary dose interruption; reinitiate at 50% of previous dose | Discontinue everolimus |
Myelosuppression [19]  Platelets  Neutrophils |  | Temporary dose interruption until recovery to grade ≤1; reinitiate at same dose No dose adjustment required | Temporary dose interruption until recovery to grade ≤1; reinitiate at 50% of previous dose Temporary dose interruption until recovery to grade ≤2; reinitiate at same dose | Temporary dose interruption until recovery to grade ≤1; reinitiate at 50% of previous dose Temporary dose interruption until recovery to grade ≤2; reinitiate at 50% of previous dose |
Febrile neutropenia [19] | - | - | Temporary dose interruption until recovery to grade ≤2 (≥1.25 × 109/L) and no fever; reinitiate at approximately 50% of previous dose | Discontinue everolimus |