Clinicians Evaluate Second-Line Renal Cell Carcinoma Treatments

Cabozantinib and Nivolumab Regime Precedes Disease Progression

A patient with renal cell carcinoma experienced disease progression after approximately 14 months on cabozantinib plus nivolumab.

The patient had previously achieved tumor shrinkage and stable disease, alongside treatment-related hypothyroidism managed with medication. Following this progression, the patient faced an ECOG performance status of 1 and a lack of available clinical trials.

Key Clinical Takeaways:

• Tivozanib monotherapy was preferred by 58.3% of clinicians in a recent roundtable discussion for second-line renal cell carcinoma.
• Phase 3 trial data from TiNivo-2 and CONTACT-03 indicate that adding immune checkpoint inhibitors to subsequent therapies does not improve progression-free survival.
• Lenvatinib plus everolimus demonstrated a median progression-free survival of 15.7 months in the LenCabo trial, though toxicity remains a clinical consideration.

Subsequent Treatment Options Evaluated by Specialists

Following disease progression, potential subsequent-line regimens included belzutifan alone, lenvatinib combined with belzutifan, lenvatinib paired with everolimus, tivozanib monotherapy, an immune checkpoint inhibitor rechallenge, or another single-agent tyrosine kinase inhibitor. At an initial treatment poll, participants were evenly divided among lenvatinib plus belzutifan, lenvatinib plus everolimus, and tivozanib. Each of these three approaches was selected by 4 of 12 respondents, representing 33.3% of the total. No participants selected an immune checkpoint inhibitor rechallenge.

For Christopher Wee, MD, of Cleveland Clinic Taussig Cancer Center, the priority was maximizing treatment benefit. “Obviously [we want] overall survival [OS], but [also] durability of response in the second line [to] try to get as much mileage as we can,” he said, favoring lenvatinib plus everolimus while awaiting regulatory clarity on lenvatinib plus belzutifan.

Mark Knapp, MD, of Zangmeister Cancer Center, emphasized tolerability and selected tivozanib, noting that lenvatinib presented tolerability issues in his prior clinical experience.

Phase 3 Trials Inform Second-Line Selections

Clinical trial evidence guided the evaluation of these therapies. The phase 3 TIVO-3 trial compared tivozanib with sorafenib in advanced renal cell carcinoma patients who had received two or three prior systemic therapies, showing improved median progression-free survival of 5.6 versus 3.9 months.

The phase 3 TiNivo-2 trial evaluated tivozanib alone or with nivolumab after prior immune checkpoint inhibitor therapy, finding a median progression-free survival of 9.2 months with tivozanib alone compared with 5.9 months for the combination. Lingbin Meng, MD, of The Ohio State University Comprehensive Cancer Center, stated that the TiNivo-2 findings increased her confidence in using tivozanib monotherapy due to a more manageable adverse event profile.

Additional evidence from the phase 3 CONTACT-03 trial showed that adding atezolizumab to cabozantinib after prior immune checkpoint inhibitor progression did not improve survival outcomes. Joseph Attallah, MD, of MetroHealth, selected lenvatinib plus everolimus based on progression-free survival results for a patient with good performance status and limited comorbidities. Meanwhile, Ike Onwere, MD, of Blanchard Valley Hospital, favored lenvatinib plus belzutifan based on supportive clinical trial data.

Participants Prefer Tivozanib for Second-Line Treatment

After reviewing the clinical evidence, tivozanib was selected by 7 of 12 participants as their preferred second-line option. Lenvatinib plus everolimus was chosen by 3 participants, while belzutifan and lenvatinib plus belzutifan each received 1 vote. Ten participants stated they were likely to use tivozanib in the second-line setting.

Regarding treatment sequencing, 8 participants selected tivozanib for second-line use, and 8 placed belzutifan in the third-line setting. The discussions emphasized that treatment sequencing depends on prior therapies, expected disease control, toxicity profiles, and patient priorities.

Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.