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Opinion|Videos|March 11, 2025

Individualized Approaches in 3L Treatment Selection for mRCC

Author(s)Pedro Barata, MD, MSc, FACP

An expert discusses how third line (3L) systemic therapy for metastatic renal cell carcinoma (mRCC) is guided by prior treatments, patient comorbidities, and drug-specific profiles. Options include tyrosine kinase inhibitors (TKIs; eg, tivozanib, cabozantinib), mTOR inhibitors (eg, everolimus), and immune-oncology– based approaches. Efficacy, tolerability (grade 3/4 adverse events [AEs]), and pharmacokinetic (PK) differences drive selection. Dose modifications, such as for tivozanib and lenvatinib/everolimus, balance efficacy and safety. Selection prioritizes sequencing strategy, with evidence (eg, Pal 2022) supporting reduced-dose efficacy.

Episodes in this series

1 expert in this video

EP. 1 Case 2: Patient With Relapsed/Recurrent Metastatic RCC

1 expert in this video

EP. 2 Treatment Goals for Transitioning From 2L to 3L mRCC

1 expert in this video

EP. 3 Third-Line Treatments and Current Practice Guidelines in Advanced RCC

1 expert in this video

EP. 4 A Review of Current and Emerging Clinical Data for 3L mRCC

1 expert in this video

EP. 5 Individualized Approaches in 3L Treatment Selection for mRCC

1 expert in this video

EP. 6 Sequencing Multiple Lines of Therapy in Metastatic RCC

1 expert in this video

EP. 7 Navigating TKI Toxicities: Expert Perspectives and Clinical Distinctions

Video content above is prompted by the following:

Please discuss how you approach individualized 3L systemic therapy selection for patients with mRCC.
Please offer perspectives on the pros/cons of current options for 3L therapy.
What factors do you consider during treatment decision-making (eg, use of chemotherapy-sparing regimens, androgen receptor pathway inhibitor selection, triplet vs doublet combination systemic therapy)? For example:
- Efficacy
- Tolerability of each (eg, rate of grade 3/4 AEs)
- Patient clinical factors/comorbidities that would influence your use of each agent
- Are your 2L and 3L choices based on drug classification or on specific drugs?
- What are the similarities and differences between approved TKIs (eg, mechanism of action (MOA)/target selectivity, PK)?
How do you handle dose modifications for tivozanib?
What about for other options for mRCC (eg, lenvatinib/everolimus)?
What are the data on the efficacy of these therapies with reduced dosages (eg, Pal 2022)?

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