Alexander Chehrazi-Raffle, MD, is an assistant professor in the Department of Medical Oncology & Therapeutics Research at City of Hope.

Dr Chehrazi-Raffle on Tivozanib With/Without Nivolumab in Metastatic RCC 

“In patients who had received prior nivolumab and ipilimumab it wasn’t too surprising that we categorically saw more robust responses [among] those who then went on to receive tivozanib monotherapy.”

Alexander Chehrazi-Raffle, MD, an assistant professor in the Department of Medical Oncology & Therapeutics Research at the City of Hope, discussed findings from an exploratory analysis of the phase 3 TiNivo-2 study (NCT04987203) presented during the 

In the analysis, patients with metastatic renal cell carcinoma (RCC) received either single-agent tivozanib (Fotivda) or tivozanib in combination with nivolumab (Opdivo) following treatment with nivolumab and ipilimumab (Yervoy) or a VEGF TKI. Patients who received frontline ipilimumab plus nivolumab who then received tivozanib monotherapy (n = 37) achieved a median progression-free survival (PFS) of 9.2 months (95% CI, 4.5-not reached). Those who received first-line nivolumab and ipilimumab who went on to receive tivozanib plus nivolumab (n = 33) experienced a median PFS of 9.3 months (95% CI, 7.5-15.3).

The respective overall response rates (ORRs) were 35.1% (95% CI, 18.0%-49.8%) and 24.2% (95% CI, 11.1%-42.3%) among patients who went on to receive the second-line monotherapy or combination. There were no complete responses (CRs) in either subgroup.

Chehrazi-Raffle noted that it was not surprising that patients who had received prior nivolumab and ipilimumab achieved more robust responses with tivozanib monotherapy. These patients had never received a VEGF TKI–containing combination previously, he noted. Tivozanib monotherapy was given at a dose of 1.34 mg daily, which was higher than the 0.89-mg dose of tivozanib used in addition to nivolumab in the second-line combination, he added. These patients also performed better than those who received a VEGF TKI plus an immune checkpoint inhibitor (ICI) in the first-line setting, he concluded.

Patients who received a frontline TKI in combination with an ICI who then received tivozanib monotherapy (n = 41) achieved a median PFS of 7.4 months (95% CI, 3.7-9.3) and an ORR of 22.0% (95% CI, 10.6%-37.6%). Patients in this subgroup who went on to receive second-line tivozanib plus nivolumab (n = 42) achieved a median PFS of 3.9 months (95% CI, 2.1-5.7) and an ORR of 9.5% (95% CI, 2.7%-22.6%).

Videos

Alexander Chehrazi-Raffle, MD, discusses findings from an exploratory analysis of the TiNivo-2 trial of tivozanib with/without nivolumab in metastatic RCC.

Alexander Chehrazi-Raffle, MD, details safety data and the clinical implications of an analysis of second-line tivozanib for patients with metastatic RCC. 

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 

 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).

Alexander Chehrazi-Raffle, MD

Articles

Dr Chehrazi-Raffle on Tivozanib With/Without Nivolumab in Metastatic RCC

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