Dr Chehrazi-Raffle on the Safety of Second-Line Tivozanib With/Without Nivolumab in RCC

“Tivozanib is regarded as one of the better tolerated VEGF TKIs, and we saw a similar toxicity profile in either of the arms that we looked at. The most common [adverse] effect observed was hypertension; however, it was [mostly] low grade and manageable.”

Alexander Chehrazi-Raffle, MD, an assistant professor in the Department of Medical Oncology & Therapeutics Research at the City of Hope, detailed the safety profile of second-line tivozanib (Fotivda) monotherapy with or without nivolumab (Opdivo) in patients with metastatic renal cell carcinoma (RCC), as well as clinical implications of data from a subgroup analysis of the phase 3 TiNivo-2 study (NCT04987203).

In this study, patients with metastatic RCC were previously treated with an immune checkpoint inhibitor (ICI) combination comprising nivolumab and ipilimumab (Yervoy) or a VEGF TKI and received either tivozanib monotherapy or tivozanib plus nivolumab as second-line treatment. Findings presented at the 2025 ASCO Annual Meeting showed that tivozanib was well tolerated, Chehrazi-Raffle began, adding that the agent is known as one of the better tolerated VEGF TKIs.He noted that the most common adverse effect seen with tivozanib monotherapy was low-grade hypertension, which was manageable.

Of note, patients who were treated with a TKI plus ICI in the first-line setting demonstrated a median progression-free survival (PFS) of 7.4 months (95% CI, 3.65-9.33) with second-line tivozanib monotherapy (n = 41) and 3.91 months (95% CI, 2.14-6.74) with nivolumab plus tivozanib (n = 42), respectively. Additionally, the objective response rate (ORR) was 22% (95% CI, 10.6%-37.6%) vs 9.5% (95% CI, 2.7%-22.6%) in these respective arms.

Based on these data, second-line tivozanib monotherapy should be considered following disease progression on an immune-oncology combination in the first-line setting for metastatic RCC, Chehrazi-Raffle emphasized. He noted that the outcomes from TiNivo-2 were similar to those from the CONTACT-03 trial (NCT04338269), which failed to show a survival benefit with the addition of atezolizumab (Tecentriq) to cabozantinib vs cabozantinib alone in patients with RCC.

In the subgroup analysis, patients who specifically received nivolumab plus ipilimumab in the first line had a median PFS of 9.20 months (95% CI, 4.5-not reached) in the tivozanib monotherapy (n = 37) and 9.33 months (95% CI, 7.26-15.34) in the tivozanib plus nivolumab (n = 33) arms, respectively (HR, 1.05; 95% CI, 0.51-1.95).