Therapeutic Sequencing for Relapsed/Refractory Metastatic Renal Cell Carcinoma: The Case of a 65-year-old Patient

An expert discusses the patient case of a 65-year-old woman who has presented to the emergency department with abdominal pain. The patient’s previous medical issues include a duodenal ulcer that she experienced 10 years ago. The patient is a smoker, and her current medication is lansoprazole (30 mg). After the patient begins to present worsening lower back pain, a CT scan shows lytic lesions in her thoracic spine and rounded lesion in both lungs. A biopsy of the lung lesion confirms clear cell renal cell carcinoma (RCC) with sarcomatoid differentiation.

An expert discusses how, in third line (3L) therapy, goals shift from optimal disease control to managing treatment-resistant disease while preserving quality of life. Unlike 2L therapy where significant disease control is still expected, 3L aims for modest clinical benefit, symptomatic relief, and stabilizing disease progression. Treatment choices now heavily prioritize tolerability, patient preferences, and palliative considerations.

A panelist discusses how, based on the NCCN guidelines for kidney cancer, third-line treatment options for this patient include cabozantinib, lenvatinib plus everolimus, tivozanib, and everolimus monotherapy. Clinical trials and best supportive care remain important considerations at this stage.

An expert discusses how efficacy and safety data from trials such as METEOR, TIVO-3, TiNivo-2, and LITESPARK-005 guide third line (3L) renal cell carcinoma (RCC) treatment. Differences in trial populations, evolving long-term trends, and prior immune checkpoint inhibitor (ICI) use impact applicability. CONTACT-03 and TiNivo-2 provide key insights, and real-world data and patient-reported outcomes refine clinical decision-making. Community oncologists should critically assess study limitations and evolving evidence when selecting therapy.

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.

An expert discusses using sequence therapies based on disease progression, patient factors, and resistance mechanisms. After a first-line tyrosine kinase inhibitor plus immune checkpoint inhibitor (TKI +  ICI) regimen, preferred subsequent-line options include alternative TKIs, chemotherapy, or combination strategies, tailored to patient response and tolerability.

An expert discusses how medical professionals counsel patients on adverse event (AE) risks with tyrosine kinase inhibitors (TKIs) such as lenvatinib/everolimus by highlighting key safety distinctions, including hypertension (HTN), fatigue, and diarrhea. For third-line tivozanib, tolerability and common toxicities (eg, Palmar-Plantar Erythrodysesthesia (PPE), HTN) are considered. AE incidence, discontinuation rates, and drug interactions guide treatment choices. Managing toxicities involves prevention, monitoring, and mitigation strategies, with dose modifications tailored based on severity and combination regimens. Community oncologists are advised on proactive AE management to optimize outcomes.