Skip to content
Back to full profile

FGFR inhibitor

Erdafitinib

Balversa · Erda

FGFR inhibitor · approved 2019 · 7 references

The first FGFR inhibitor in urothelial cancer — on-target FGFR1 blockade drives hyperphosphatemia.

Signature injury
Electrolyte Disturbance
Severity
Moderate
Reversibility
Reversible
Onset
Early — typically within the first 1-2 cycles, used to guide pharmacodynamic up-titration.

Signature kidney injury & incidence

Electrolyte Disturbance — representative incidence ~73% (73–78% range across studies).

Hyperphosphatemia is the most common, on-target class adverse event — reported in ~73-78% of treated patients across studies and used as a pharmacodynamic marker for protocol-driven dose up-titration. Grade >=3 hyperphosphatemia is much less frequent (~2%).

Source: Nishina et al., Invest New Drugs 2017

Reported injury signatures: Electrolyte Disturbance.

Onset timing & rechallenge

Subacute (~1–6 weeks) — Early — typically within the first 1–2 cycles (on-target hyperphosphatemia used to guide up-titration).

Mechanism of kidney injury

FGFR1 inhibition disrupts the FGF23-Klotho-FGFR1 axis that normally suppresses proximal-tubular phosphate reabsorption (by down-regulating the NaPi-2a/2c cotransporters) and inhibits 1-alpha-hydroxylase. Blocking this signaling increases tubular phosphate reabsorption and raises serum phosphate; sustained hyperphosphatemia with a high calcium-phosphate product risks soft-tissue and vascular calcification (including calcinosis cutis) and nephrocalcinosis.

Clinical presentation

Asymptomatic hyperphosphatemia detected on routine labs, often within the first 2-3 weeks; may be accompanied by an elevated calcium-phosphate product. Severe/persistent cases risk metastatic mineral deposition; non-renal effects (stomatitis, nail and skin changes, central serous retinopathy) are common.

Management

Per label: if phosphate exceeds ~5.5 mg/dL, restrict dietary phosphate and start an oral phosphate binder (e.g. sevelamer); for higher thresholds (~7-10 mg/dL or symptoms) interrupt and dose-reduce, and discontinue for persistent levels >10 mg/dL despite intervention. Up-titrate the dose at day 14-21 only if phosphate is <5.5 mg/dL and no significant toxicity.

Risk factors

  • Higher dose / up-titration to 9 mg
  • Pre-existing CKD
  • High dietary phosphate or phosphate supplements

Prevention

  • Serum phosphate monitoring with protocol-based dose titration
  • Low-phosphate diet (~600-800 mg/day) when phosphate rises
  • Avoid phosphate-containing supplements/laxatives

Renal dose adjustment

No starting-dose change for mild-moderate renal impairment; severe impairment and dialysis are not well studied (use with caution). The principal 'dose adjustment' is phosphate-guided titration/interruption rather than a CrCl-based rule.

Dialyzability & ESKD dosing

Highly protein-bound oral small molecule; not expected to be appreciably dialyzed. No validated ESKD dosing — phosphate handling is also altered in ESKD, complicating the pharmacodynamic phosphate biomarker.

Differential diagnosis

FGFR-inhibitor hyperphosphatemia (on-target, early, isolated, dose-related) vs hyperphosphatemia of CKD/ESKD, tumor lysis (accompanied by hyperuricemia/hyperkalemia and AKI), or exogenous phosphate load. The temporal link to dosing and use as a PD marker are characteristic.

Monitoring

  • Serum phosphate at baseline and every 2-3 weeks early (then monthly) to drive dose titration
  • Serum calcium and calcium-phosphate product
  • Ophthalmologic exams for central serous retinopathy; routine creatinine

Key trials & series

  • BLC2001 (registrational FGFR-altered urothelial carcinoma)
  • THOR (erdafitinib vs chemotherapy/pembrolizumab in urothelial carcinoma)
  • RAGNAR (tumor-agnostic FGFR-altered solid tumors)
  • Siefker-Radtke 2023 BLC2001 TEAE-management analysis

Clinical pearls

  • Hyperphosphatemia here is an expected on-target FGFR1 effect and a dosing biomarker — not idiosyncratic toxicity — and is actually used to confirm adequate target engagement before up-titration.
  • Manage with diet and binders first; reserve dose interruption/reduction for higher thresholds.
  • Sustained high calcium-phosphate product can cause calcinosis cutis and nephrocalcinosis — keep the product down, not just the phosphate.

Anticancer mechanism

Oral pan-FGFR (FGFR1-4) tyrosine kinase inhibitor; blocks oncogenic FGFR signaling in FGFR-altered tumors. Approved for FGFR2/3-altered locally advanced or metastatic urothelial carcinoma.

Guidelines & consensus

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

  • ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
  • SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
  • ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
  • ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
  • ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
  • KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
  • KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
  • KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525

References

7 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions.Katoh M et al. · Nat Rev Clin Oncol · 2024 · PMID 38424198
  2. 2.Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors.Nishina T et al. · Invest New Drugs · 2017 · PMID 28965185
  3. 3.Management of Fibroblast Growth Factor Inhibitor Treatment-emergent Adverse Events of Interest in Patients with Locally Advanced or Metastatic Urothelial Carcinoma.Siefker-Radtke AO et al. · Eur Urol Open Sci · 2023 · PMID 37101768
  4. 4.Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study.Pant S et al. · Lancet Oncol · 2023 · PMID 37541273
  5. 5.Safety and efficacy of the pan-FGFR inhibitor erdafitinib in advanced urothelial carcinoma and other solid tumors: A systematic review and meta-analysis.Zheng X et al. · Front Oncol · 2023 · PMID 36776367
  6. 6.Calcinosis cutis dermatologic toxicity associated with fibroblast growth factor receptor inhibitor for the treatment of Wilms tumor.Arudra K et al. · J Cutan Pathol · 2018 · PMID 30021048
  7. 7.Current Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features.Tonooka A et al. · J Nippon Med Sch · 2021 · PMID 34840210
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.