Introduction
Inlyta (axitinib) is an oral, small-molecule tyrosine kinase inhibitor developed by Pfizer Inc. for the treatment of advanced renal cell carcinoma (RCC). Approved by the FDA in 2012, it represents a second-line treatment option for patients who have failed prior systemic therapy. As a targeted therapy, Inlyta specifically inhibits vascular endothelial growth factor receptors (VEGFRs), playing a crucial role in the management of advanced kidney cancer.
Mechanism of Action
Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3. These receptors are implicated in pathologic angiogenesis, tumor growth, and metastatic progression of cancer. By binding to the intracellular ATP-binding domain of these receptors, axitinib inhibits VEGF-mediated endothelial cell proliferation and survival, thereby reducing tumor vascularization and limiting blood supply to malignant cells.
Indications
- Treatment of advanced renal cell carcinoma after failure of one prior systemic therapy
- First-line treatment of advanced renal cell carcinoma in combination with pembrolizumab (FDA-approved 2019)
- First-line treatment of advanced renal cell carcinoma in combination with avelumab (FDA-approved 2019)
Dosage and Administration
Standard dosing: 5 mg orally twice daily without regard to meals Dose titration: Based on safety and tolerability, may increase to 7 mg twice daily and subsequently to 10 mg twice daily Dose modification: Recommended for management of adverse reactions Special populations:- Hepatic impairment: Reduce starting dose in moderate hepatic impairment (Child-Pugh Class B)
- Renal impairment: No dosage adjustment necessary
- Elderly patients: No dosage adjustment required based on age alone
Pharmacokinetics
Absorption: Oral bioavailability approximately 58%; Tmax 2.5-4.1 hours Distribution: Volume of distribution 160 L; >99% protein bound Metabolism: Primarily hepatic via CYP3A4/5 and to a lesser extent CYP1A2, CYP2C19, and UGT1A1 Elimination: Primarily fecal (41%) and renal (23%); terminal half-life 2.5-6.1 hoursContraindications
- Hypersensitivity to axitinib or any component of the formulation
Warnings and Precautions
Boxed Warning: None Important warnings:- Hypertension: Monitor blood pressure regularly and treat as needed
- Arterial thromboembolic events: Discontinue if severe events occur
- Venous thromboembolic events: Monitor for signs and symptoms
- Hemorrhagic events: Serious and sometimes fatal hemorrhages have occurred
- Cardiac failure: Monitor for signs or symptoms of cardiac failure
- Gastrointestinal perforation and fistula: Discontinue if perforation or fistula occurs
- Thyroid dysfunction: Monitor thyroid function before and during treatment
- Wound healing complications: Withhold at least 24 hours prior to elective surgery
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue if diagnosed
- Proteinuria: Monitor urine protein regularly
- Hepatic impairment: Reduce starting dose in moderate hepatic impairment
Drug Interactions
Strong CYP3A4 inhibitors: Avoid concomitant use (e.g., ketoconazole, itraconazole, clarithromycin) Strong CYP3A4 inducers: Avoid concomitant use (e.g., rifampin, dexamethasone, phenytoin) Moderate CYP3A4 inhibitors/inducers: May require dose adjustment Acid-reducing agents: Proton pump inhibitors may decrease axitinib exposureAdverse Effects
Very common (≥20%):- Diarrhea (55%)
- Hypertension (40%)
- Fatigue (39%)
- Decreased appetite (34%)
- Nausea (32%)
- Dysphonia (31%)
- Palmar-plantar erythrodysesthesia syndrome (27%)
- Weight decreased (25%)
- Vomiting (24%)
- Constipation (20%)
- Hemorrhagic events (3%)
- Arterial thromboembolic events (1%)
- Venous thromboembolic events (3%)
- Gastrointestinal perforation (0.3%)
- Cardiac failure (1%)
Monitoring Parameters
- Blood pressure: Weekly for first 6 weeks, then regularly
- Thyroid function: Baseline and periodically during treatment
- Urine protein: Baseline and periodically during treatment
- Liver function tests: Regularly during treatment
- Complete blood count: Regularly during treatment
- Signs/symptoms of heart failure, bleeding, thromboembolism, GI perforation
- Wound healing complications
Patient Education
- Take exactly as prescribed, approximately 12 hours apart with or without food
- Do not crush or break tablets
- Report any signs of bleeding, severe diarrhea, or persistent hypertension
- Monitor blood pressure regularly as directed by healthcare provider
- Immediately report symptoms of heart problems (shortness of breath, chest pain)
- Inform all healthcare providers about Inlyta treatment before any surgical procedures
- Use effective contraception during treatment and for at least 1 week after final dose
- Report any voice changes or difficulty speaking
- Notify provider of all other medications, including over-the-counter drugs and supplements
- Be aware of potential side effects and report any new or worsening symptoms
References
1. FDA Prescribing Information: Inlyta (axitinib). Revised 2022. 2. Rini BI, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013;14(6):552-562. 3. Motzer RJ, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013;14(13):1287-1294. 4. Rini BI, et al. AXIS: A randomized trial of axitinib (AG-013736) or sorafenib (SOR) as second-line therapy in metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2010;28:15s. 5. NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer. Version 2.2023. 6. Rini BI, et al. Diastolic blood pressure as a biomarker of axitinib efficacy in solid tumors. Clin Cancer Res. 2011;17(11):3841-3849.