Table 3.
Dose modification schemes for adverse reactions
| Adverse reaction | Dose modification |
|---|---|
| Erdafitinib4 | |
| Hyperphosphatemia | |
| Limit daily phosphate intake to 600–800 mg for all patients | |
| Serum phosphate 5.6–6.9 mg/dL | Maintain current dose of erdafitinib. |
| Serum phosphate 7.0–9.0 mg/dL | Withhold erdafitinib and assess serum phosphate concentration weekly. When the concentration is <5.5 mg/dL (or ≤ the patient’s baseline concentration), restart the same dose of erdafitinib. If the hyperphosphatemia lasted >1 week, then erdafitinib dose may be reduced. |
| Serum phosphate >9.0 mg/dL | Withhold erdafitinib and assess serum phosphate concentration weekly. When the concentration is <5.5 mg/dL (or ≤ the patient’s baseline concentration), restart erdafitinib 1 dose level lower than the previous dosage. |
| More than 10.0 mg/dL or significant alteration in baseline renal function or grade 3 hypercalcemia | Withhold erdafitinib and assess serum phosphate concentration weekly. When the concentration is <5.5 mg/dL (or ≤ the patient’s baseline concentration), restart erdafitinib 2 dose levels below the previous dosage. |
| Central serous retinopathy (CSR)/retinal pigment epithelial detachment (RPED) | |
| Grade 1: asymptomatic; clinical, or diagnostic observations only | Withhold erdafitinib until resolution. Resume at 1 dose level lower if CSR/RPED resolves within 4 weeks. Consider re-escalating dose if no CSR/RPED recurrence for a month. If CSR/RPED remains stable for 2 consecutive eye exams but has not resolved, then resume erdafitinib at the next lower dose level. |
| Grade 2: visual acuity 20/40 or better or ≤3 lines of decreased vision from baseline | Withhold erdafitinib until resolution. May resume at 1 dose level lower if CSR/RPED resolves within 4 weeks |
| Grade 3: visual acuity worse than 20/40 or >3 lines of decreased vision from baseline | Withhold erdafitinib until resolution. May resume at 2 dose levels lower if CSR/RPED resolves within 4 weeks. Consider permanent discontinuation if CSR/RPED recurs. |
| Grade 4: visual acuity 20/200 or worse in the affected eye | Permanently discontinue erdafitinib. |
| Other adverse reactions | |
| Grade 3 | Withhold erdafitinib until resolution to grade 1 or baseline. Then, erdafitinib may be resumed at 1 dose level lower. |
| Grade 4 | Permanently discontinue erdafitinib. |
| Pemigatinib5 | |
| Hyperphosphatemia | |
| Serum phosphate >7 to ≤10 mg/dL | Start phosphate-lowering therapy; measure serum phosphate levels weekly. Withhold pemigatinib if levels do not return to <7 mg/dL within 2 weeks of initiating phosphate-lowering therapy. After the first occurrence, resume pemigatinib at the same dose when phosphate levels are <7 mg/dL; after subsequent recurrences, resume pemigatinib at a lower dose level. |
| Serum phosphate >10 mg/dL | Start phosphate-lowering therapy; measure serum phosphate levels weekly. Withhold pemigatinib if levels do not return to ≤10 mg/dL within 1 week of initiating phosphate-lowering therapy. When phosphate levels are <7 mg/dL, resume pemigatinib at 1 dose level lower. If serum phosphate >10 mg/dL recurs following 2 dose reductions, permanently discontinue pemigatinib. |
| Retinal pigment epithelial detachment (RPED) | |
| Continue pemigatinib if RPED is stable on serial examination and asymptomatic. Withhold pemigatinib if RPED is worsening on serial examination or symptomatic. Resume pemigatinib at a lower dose if RPED is improved on subsequent examination and asymptomatic. Consider permanently discontinuing pemigatinib, based on clinical status, if examination does not improve or symptoms persist. | |
| Other adverse reactions | |
| Grade 3 | Withhold pemigatinib until resolution to grade 1 or baseline. If resolution occurs within 2 weeks, resume pemigatinib at 1 dose lower. If resolution does not occur within 2 weeks, permanently discontinue pemigatinib. If grade 3 AEs recur after 2 dose reductions, permanently discontinue pemigatinib. |
| Grade 4 | Permanently discontinue pemigatinib. |
| Futibatinib6 | |
| Hyperphosphatemia | |
| Serum phosphate ≥5.5 to ≤7 mg/dL | Initiate phosphate-lowering therapy and continue futibatinib at the current dose. Monitor serum phosphate levels weekly. |
| Serum phosphate >7 to ≤10 mg/dL | Initiate or adjust phosphate-lowering therapy. Monitor serum phosphate levels weekly and reduce futibatinib to the next lower dose. If the serum phosphate concentration resolves to ≤7 mg/dL within 2 weeks after dose reduction, continue at this reduced dose. If serum phosphate concentration does not reach ≤7 mg/dL within 2 weeks, further reduce futibatinib to the next lower dose. If serum phosphate concentration does not reach ≤7 mg/dL within 2 weeks after the second dose reduction, withhold futibatinib until serum phosphate concentration is ≤ 7 mg/dL and resume at the dose prior to treatment interruption. |
| Serum phosphate >10 mg/dL | Withhold futibatinib until serum phosphate concentration is ≤7 mg/dL and resume futibatinib at the next lower dose; initiate or adjust phosphate-lowering therapy and monitor serum phosphate levels weekly. Permanently discontinue futibatinib if serum phosphate concentration does not reach ≤7 mg/dL within 2 weeks following 2 dose interruptions and reductions. |
| RPED | |
| Continue futibatinib at the current dose and continue periodic ophthalmic evaluation. If RPED resolves within 14 days, continue futibatinib at the current dose. If RPED does not resolve within 14 days, withhold futibatinib until RPED resolves, then resume futibatinib at previous or lower dose. | |
| Other adverse reactions | |
| Grade 3 | Withhold futibatinib until toxicity resolves to grade 1 or baseline. For hematologic toxicities resolving within 1 week, resume futibatinib at the dose prior to dose interruption. For other adverse reactions, resume futibatinib at the next lower dose. |
| Grade 4 | Permanently discontinue futibatinib. |
| Starting dose | Dose reductions |
|||||
|---|---|---|---|---|---|---|
| First | Second | Third | Fourth | Fifth | ||
| Erdafitiniba,4 | 9 mg QD (three 3-mg tablets) | 8 mg QD (two 4-mg tablets) | 6 mg QD (two 3-mg tablets) | 5 mg QD (one 5-mg tablet) | 4 mg QD (one 4-mg tablet) | discontinue erdafitinib |
| Pemigatinib5 | 13.5 mg (one 13.5-mg tablet) QD for first 14 days of each 21-day cycle | 9 mg (one 9-mg tablet) QD for first 14 days of each 21-day cycle | 4.5 mg (one 4.5-mg tablet) QD for first 14 days of each 21-day cycle | discontinue pemigatinib | ||
| Futibatinib6 | 20 mg QD (five 4-mg tablets) | 16 mg QD (four 4-mg tablets) | 12 mg QD (three 4-mg tablets) | discontinue futibatinib | ||
QD, once daily.
a
Patients may also start at 8 mg QD and, if needed, decrease dosage from there.