Treatment Selection After Progression
Following disease progression on cabozantinib plus nivolumab, participants at a clinical roundtable reviewed subsequent-line therapy choices for advanced renal cell carcinoma, Targeted Onc reported.
The patient had developed treatment-related hypothyroidism and experienced progression after approximately 14 months with an ECOG performance status of 1.
Available subsequent-line options included belzutifan, lenvatinib plus belzutifan, lenvatinib plus everolimus, tivozanib, immune checkpoint inhibitor rechallenge, or another single-agent tyrosine kinase inhibitor. At the initial treatment poll, participants were evenly divided among lenvatinib plus belzutifan, lenvatinib plus everolimus, and tivozanib, each selected by 4 of 12 respondents.
Doctors Prioritize Survival and Tolerability in Treatment Selection
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.
Mark Knapp, MD, of Zangmeister Cancer Center considered efficacy alongside tolerability. He selected tivozanib, noting previous issues with lenvatinib tolerability and describing tivozanib as effective and well tolerated in the second-line setting.
Trial Evidence Informing Choices
The phase 3 TIVO-3 trial compared tivozanib with sorafenib in advanced renal cell carcinoma patients who received 2 or 3 prior systemic therapies, improving median progression-free survival to 5.6 months versus 3.9 months, though final overall survival showed no significant difference, according to data cited by Targeted Onc.
The phase 3 TiNivo-2 trial evaluated tivozanib alone or with nivolumab after prior immune checkpoint inhibitor therapy. Adding nivolumab did not improve outcomes, as median progression-free survival reached 9.2 months with tivozanib alone compared with 5.9 months for the combination.
The phase 3 CONTACT-03 trial provided evidence against immune checkpoint inhibitor rechallenge, showing that adding atezolizumab to cabozantinib after prior progression did not improve progression-free survival or overall survival compared with cabozantinib alone. The phase 3 LITESPARK-005 trial compared belzutifan with everolimus, showing identical median progression-free survival of 5.6 months at the first interim analysis.
Post-Discussion Tivozanib Preference
After reviewing clinical trial evidence, tivozanib was selected by 7 of 12 participants as their preferred second-line option. Lenvatinib plus everolimus was selected by 3 participants, while belzutifan and lenvatinib plus belzutifan each received 1 vote.
Regarding treatment sequencing, 8 participants selected tivozanib for second-line use, while 8 placed belzutifan in the third-line setting. The discussion emphasized that treatment sequencing depends heavily on prior therapies, expected disease control, and patient priorities.
Frequently Asked Questions
What common adverse events are associated with belzutifan therapy?
Anemia and hypoxia are identified as important belzutifan-associated adverse events that can affect clinical treatment decisions.
How did lenvatinib plus everolimus perform in trial comparisons?
In the randomized phase 2 LenCabo trial, lenvatinib plus everolimus achieved a median progression-free survival of 15.7 months compared with 10.2 months for cabozantinib after prior immune checkpoint inhibitor therapy.
Why was immune checkpoint inhibitor rechallenge discouraged by trial results?
Data from the CONTACT-03 trial demonstrated that adding atezolizumab to cabozantinib after prior immune checkpoint inhibitor progression failed to improve progression-free survival or overall survival compared with cabozantinib alone.
Keep reading