FGFR inhibitor
Infigratinib
Truseltiq · INFI
FGFR inhibitor · approved 2021 · 7 references
An FGFR inhibitor whose hyperphosphatemia is an on-target pharmacodynamic biomarker — manage it, do not ignore it.
- Signature injury
- Electrolyte Disturbance
- Severity
- Moderate
- Reversibility
- Reversible
- Onset
- Early (first cycle); reversible and dose-dependent, normalizing during the 7-day off-drug interval of the 21-on/7-off cycle.
Signature kidney injury & incidence
Electrolyte Disturbance — representative incidence ~77%.
Hyperphosphatemia is the most common adverse event and the defining FGFR class effect — it occurred in 83 of 108 patients (~77%, any grade) in the pivotal trial. Infigratinib-specific nephrocalcinosis/calciphylaxis rates are not quantified (case reports/series only).
Source: Javle et al., Lancet Gastroenterol Hepatol 2021
Reported injury signatures: Electrolyte Disturbance, Crystal / Obstructive Nephropathy.
Renal toxicity profile
- Electrolyte DisturbancePrimary~77%Hyperphosphatemia ~77% (83/108) - on-target FGFR class effect and most common AE
- Crystal / Obstructive NephropathyRare
Onset timing & rechallenge
Subacute (~1–6 weeks) — Early (first cycle); reversible and dose-dependent, normalizing during the 7-day off-drug interval.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- Higher dose/exposure
- Pre-existing CKD or reduced GFR and baseline hyperphosphatemia
- High dietary phosphate
- Concurrent vitamin D or phosphate supplementation
Prevention
- Low-phosphate diet (~600-800 mg/day) from the start
- Avoid vitamin D loading
- Start an oral phosphate binder when phosphate exceeds the label threshold (~7.0 mg/dL)
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- Serum phosphate at baseline and regularly (at least monthly) with a threshold-based binder/hold algorithm
- Serum calcium and renal function
- Ophthalmologic monitoring for serous retinopathy (FGFR class effect; outside renal scope)
Key trials & series
- Pivotal phase 2 (Javle, Lancet Gastroenterol Hepatol 2021) — hyperphosphatemia in ~77%
- PROOF 301 confirmatory phase 3 (Makawita, Future Oncol 2020) — design/rationale
Clinical pearls
- Hyperphosphatemia is an on-target pharmacodynamic biomarker of FGFR inhibition, not idiosyncratic — but it must be managed.
- It is the most common adverse event (~77% any grade) and the defining class effect of all FGFR1-3 inhibitors.
- Manage proactively with a low-phosphate diet plus threshold-triggered binders; the 7-day off-drug window aids reversal.
- The feared downstream harm is calcium-phosphate deposition (nephrocalcinosis, calcinosis cutis, calciphylaxis) — keep the calcium-phosphate product down and avoid vitamin D loading.
Anticancer mechanism
Note
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.Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study.Javle M et al. · Lancet Gastroenterol Hepatol · 2021 · PMID 34358484
- 2.Targeted Therapy for Advanced or Metastatic Cholangiocarcinoma: Focus on the Clinical Potential of Infigratinib.Yu J et al. · Onco Targets Ther · 2021 · PMID 34720591
- 3.The Klotho proteins in health and disease.Kuro-O M et al. · Nat Rev Nephrol · 2019 · PMID 30455427
- 4.Pleiotropic Actions of FGF23.Erben RG et al. · Toxicol Pathol · 2017 · PMID 29096595
- 5.Calcinosis Cutis With Selective Fibroblast Growth Factor Receptor Inhibitors: A Case Report and Review of Literature.Ghimire B et al. · Cureus · 2025 · PMID 40486452
- 6.Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial.Makawita S et al. · Future Oncol · 2020 · PMID 32580579
- 7.Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.Prud'homme GJ et al. · Front Aging · 2022 · PMID 35903083