TRK/ROS1 TKI
Entrectinib
Rozlytrek · ENTR
TRK/ROS1 TKI · approved 2019 · 4 references
A TRK/ROS1 TKI that nudges creatinine up by curbing tubular secretion — a benign pseudo-AKI pattern.
- Signature injury
- Pseudo-AKI
- Severity
- Mild
- Reversibility
- Reversible
- Onset
- Within the first weeks of therapy; reversible on discontinuation.
Signature kidney injury & incidence
Pseudo-AKI.
A mild blood-creatinine increase is recognized and is attributed to reduced tubular creatinine secretion rather than true GFR decline (a pseudo-AKI pattern). It is typically modest, early and reversible; a meaningful structural-AKI rate is not established.
Source: Topletz-Erickson et al., J Clin Pharmacol 2020 (transporter analog); Nakada et al., Drug Metab Dispos 2023
Reported injury signatures: Pseudo-AKI.
Onset timing & rechallenge
Subacute (~1–6 weeks) — Creatinine change appears within the first weeks of therapy and is reversible on discontinuation.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- Baseline CKD (makes the creatinine shift more conspicuous)
- Concurrent drugs affecting creatinine secretion
Prevention
- Anticipate the benign creatinine rise; avoid unnecessary interruption
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
Monitoring
- Serum creatinine with cystatin C as a confirmatory test if a rise prompts concern
- Urinalysis (expected bland)
- QTc and LVEF per label (the clinically important toxicities)
Key trials & series
- Integrated ALKA/STARTRK-1/STARTRK-2 analyses — registrational efficacy/safety (clinical context)
- Mercier, Cancer Chemother Pharmacol 2022 — exposure-response analysis supporting the 600 mg/day dose (clinical/safety context)
Clinical pearls
- Like tucatinib, entrectinib raises creatinine via blocked proximal-tubular secretion — confirm with cystatin C and keep treating.
- The dominant real toxicities are QTc prolongation, weight gain and CNS effects, not the kidney.
- Don't dose-reduce or stop for an isolated stable creatinine bump with a bland urinalysis.
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 Summaries may be superseded; consult the current full text and individualize to the patient.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
4 peer-reviewed references. Citation metadata via PubMed / NLM.
- 1.Efficacy and safety exposure-response analyses of entrectinib in patients with advanced or metastatic solid tumors.Mercier F et al. · Cancer Chemother Pharmacol · 2022 · PMID 35118559
- 2.Tucatinib Inhibits Renal Transporters OCT2 and MATE Without Impacting Renal Function in Healthy Subjects.Topletz-Erickson AR et al. · J Clin Pharmacol · 2020 · PMID 32989831
- 3.Quantitative Consideration of Clinical Increases in Serum Creatinine Caused by Renal Transporter Inhibition.Nakada T et al. · Drug Metab Dispos · 2023 · PMID 36859345
- 4.Onconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens · 2024 · PMID 38095483
Case reports & series (3)
The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.
- C1.[C · Limited]Case Report: A case of complete response to entrectinib in NTRK fusion gene-positive parotid gland cancer.Moriyama E et al. · Front Oncol · 2023 · PMID 37601665
- C2.[C · Limited]TRK Inhibition with Entrectinib in Metastatic Salivary Secretory Carcinoma (SC): A Case Report.Ernst MS et al. · Curr Oncol · 2022 · PMID 35735423
- C3.[C · Limited]Entrectinib-Induced Heart Failure in a Patient With Metastatic Lung Adenocarcinoma: A Case Report.Otsu Y et al. · Cureus · 2022 · PMID 36605067