What are the common side effects of futibatinib?

Common Side Effects of Futibatinib

The most common side effect of futibatinib is hyperphosphatemia (increased phosphate levels in the blood), which occurs in approximately 82-97% of patients, with grade 3 or higher hyperphosphatemia occurring in 19-39% of cases. 1, 2, 3

Major Side Effect Categories

Very Common Side Effects (>50%)

• Hyperphosphatemia (82-97%):
  • Typically occurs early (median time to onset of grade ≥3: 9 days)
  • Usually resolves to grade ≤2 within 7 days with appropriate management
  • May require phosphate-lowering medications and dose adjustments 3

Common Side Effects (10-50%)

• Nail disorders (27%): Changes in nail appearance or structure 2, 3
• Hepatic adverse events (27%):
  • Increased alanine aminotransferase (50% overall, 7% grade ≥3)
  • Increased aspartate aminotransferase (46% overall, 13% grade ≥3)
  • Increased alkaline phosphatase (47% overall, 4.9% grade ≥3)
  • Increased bilirubin (28% overall) 1, 3
• Stomatitis/mouth sores (19%): Inflammation of the mouth and lips 2, 3
• Diarrhea (33.5%) 4
• Nausea (30.4%) 4
• Hand-foot syndrome/palmar-plantar erythrodysesthesia (13%): Redness, swelling, and pain on the palms and soles 2, 3

Less Common Side Effects (<10%)

• Rash (9%) 2, 3
• Retinal disorders (8%): Changes in the back of the eye 2, 3
• Cataracts (4%): Clouding of the lens of the eye 2, 3
• Hematologic abnormalities:
  • Decreased hemoglobin (52% overall, 6% grade ≥3)
  • Decreased lymphocytes (46% overall, 10% grade ≥3)
  • Decreased platelets (42% overall, 1% grade ≥3)
  • Decreased leukocytes (33% overall, 1.1% grade ≥3)
  • Decreased neutrophils (31% overall, 1.6% grade ≥3) 1

Timing and Management

The onset of side effects varies considerably:

• Early-onset side effects: Hyperphosphatemia (median 9 days)
• Later-onset side effects: Cataracts (median 125 days) 3

Most side effects are manageable with:

1. Dose interruptions
2. Dose reductions
3. Supportive care measures
4. For hyperphosphatemia: phosphate-lowering medications 3

Clinical Implications

• Most side effects are mild to moderate in severity and reversible
• Only 2% of patients discontinue treatment due to treatment-related adverse events
• No treatment-related deaths have been reported in clinical trials 2, 3
• Monitoring of phosphate levels is essential, especially during the first few weeks of treatment
• Regular liver function tests are important due to the potential for hepatic adverse events
• Eye examinations may be warranted to monitor for retinal disorders and cataracts

Special Considerations

• Patients with cirrhosis and elevated total bilirubin (>1.5 × ULN to 3 × ULN) may experience increased adverse reactions due to higher unbound futibatinib exposure 1
• Drug interactions: Avoid concomitant use with dual P-gp and strong CYP3A inhibitors or inducers, as they may alter futibatinib exposure 1
• Futibatinib may increase exposure of drugs that are substrates of P-gp or BCRP, requiring more frequent monitoring for adverse reactions with these medications 1

The side effect profile of futibatinib appears manageable with appropriate monitoring and interventions, allowing most patients to continue treatment with this medication.