}

Erdafitinib

Chemotherapies

Drug Overview

Erdafitinib (brand name Balversa) is a targeted small-molecule tyrosine kinase inhibitor designed to block fibroblast growth factor receptors (FGFRs). It is the first FGFR inhibitor approved by the FDA for specific bladder cancers.

This agent is indicated for adults with locally advanced or metastatic urothelial carcinoma harboring susceptible FGFR2 or FGFR3 genetic alterations who have progressed on platinum-containing chemotherapy. By selectively binding to FGFR1–4, erdafitinib inhibits receptor phosphorylation and downstream signaling pathways.

Through FGFR blockade, erdafitinib disrupts tumor cell proliferation and survival signals, helping to control cancer progression in patients with the appropriate genetic profile.

Relevant Genes and Their Roles

The primary gene relevant to erdafitinib pharmacogenomics is CYP2C9. CYP2C9 encodes an enzyme in the cytochrome P450 family, which is responsible for oxidizing and metabolizing a variety of drugs in the liver.

Genetic variations in CYP2C9 can alter enzyme activity—some variants reduce metabolism (slower clearance), while others maintain normal function. These changes affect how quickly erdafitinib is cleared from the body, impacting drug levels, efficacy, and risk of side effects.

Impact of Genetics on Drug Response

CYP2C9 phenotype groups—from ultra-rapid to poor metabolizers—determine the rate at which erdafitinib is processed. Poor metabolizers may have slower clearance and higher systemic exposure, increasing the risk of adverse reactions. Intermediate metabolizers have moderately reduced clearance. Normal metabolizers experience expected drug levels, while ultra-rapid metabolizers may clear the drug quickly, potentially reducing effectiveness. Indeterminate results necessitate standard dosing with clinical monitoring.

Expected Clinical Effects of Genetic Variation

Ultra-rapid/Rapid Metabolizer

  • Effect on drug levels: Lower than expected plasma concentrations
  • Clinical consequence: Potential reduced efficacy of erdafitinib
  • Side effects: Generally fewer or milder adverse effects; frequency is low

Normal Metabolizer

  • Effect on drug levels: Expected therapeutic concentrations
  • Clinical consequence: Standard efficacy as observed in clinical trials
  • Side effects: Typical safety profile; mild to moderate adverse events common

Intermediate Metabolizer

  • Effect on drug levels: Moderately elevated plasma concentrations
  • Clinical consequence: Slightly increased risk of side effects without clear efficacy gain
  • Side effects: Mild to moderate; increase in frequency possible

Poor Metabolizer

  • Effect on drug levels: Significantly elevated plasma concentrations
  • Clinical consequence: Higher risk of toxicity and adverse reactions
  • Side effects: Increased severity; monitor closely for signs of toxicity

Indeterminate/Not Available

  • Effect: Unknown impact on drug metabolism
  • Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring
  • Side effects: Cannot predict; use clinical observation to manage safety

Dosing Guidelines

CYP2C9 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Normal Metabolizer No FDA guidance for this phenotype Use standard starting dose as per FDA label
Intermediate Metabolizer No FDA guidance for this phenotype Use standard starting dose as per FDA label
Poor Metabolizer May result in higher systemic concentrations and higher adverse reaction risk Monitor for adverse reactions; consider dose reduction if needed
Indeterminate / Not available No FDA guidance for this phenotype Initiate therapy with recommended starting dose

Alternative Treatment Options

No alternative drugs or dosing strategies are specified in the FDA pharmacogenomic guidance for erdafitinib. Clinicians may consider other FGFR inhibitors or standard chemotherapy regimens based on individual patient needs and current clinical guidelines.

Sources and References

Disclaimer: This document is for informational purposes only and is not a substitute for medical advice. Clinical decisions should be made by a qualified healthcare professional.

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