Real-World Data Demonstrate Efficacy, Safety With Tivozanib in mRCC

Tivozanib (Fotivda) as first-line treatment showed noninferiority compared with other tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma (mRCC) in a real-world setting. This is an attractive option for patients due to tivozanib’s tolerable safety profile, according to a presentation at the 2022 ASCO Genitourinary Cancers Symposium.

“We set out to evaluate the real-world use of tivozanib because we had some signals that this might be the preferred drug because of the toxicity profile. So, we gathered data across our 3 separate regional cancer centers from March 2017 to 2019 and looked at these outcomes,” study author Jonathan Heseltine, MBChB, of the Clatterbridge Cancer Centre in the UK, said while presenting the findings.

The retrospective trial involved 113 patients with mRCC – 82% (n = 93) with a confirmed clear cell histology, and 18% (n = 20) undefined. About half of the patients (52%; n = 59) were determined to be an intermediate prognosis per International Metastatic RCC Database Consortium (IMDC) standards. Twenty-two percent (n = 25) had favorable prognosis, and 26% (n = 29) had poor prognosis. Sixty-six percent (n = 75) had undergone a previous nephrectomy.

At a median follow-up of 25.9 months (range, 18.3-44.7 months), the overall response rate (ORR) was 29%. There were no complete responses, and 29% of patients experienced partial response, 39% stable disease, 26% progressive disease, and 6% of patients were not evaluable.

Of note, 88.5% of patients started tivozanib at the full dose, with 67% maintaining dose intensity; 11.5% started treatment with a dose reduction because of prior TKI-related toxicities or comorbidities. Median number of cycles was 7 (range, 1-33).

Median progression-free survival (PFS) was 9.0 months (95% CI, 6.0-12.1 months; P < .0001), but varied among IMDC risk groups:

• The IMDC favorable group had a median PFS of 23.0 months (95% CI, 7.6-38.4)
• The IMDC intermediate group had a median PFS of 10 months (95% CI, 6.3-13.7)
• The IMDC poor group had a median PFS of 3.0 months (95% CI, 1.5-4.5)

All-grade adverse events (AEs) were experienced in 77% of patients, with 14% being grade 3. Common AEs were: fatigue (42%; no grade 3), diarrhea (19%; <1% grade 3), mucositis (24%; 2% grade 3), anorexia (12%; <1% grade 3), and hypertension (7%; 2% grade 3) – an interesting finding, considering that the TIVO-1 clinical trial of tivozanib had a significant proportion of patients with serious grade 3 or low-level hypertension or dysphonia, which was not seen in the non-trial setting, Heseltine said.

The researchers mentioned that notable grade 3 events included abnormal liver function (3%), vascular events (2%), and seizure (<1%).

“The safety data was interesting in that we found that there were fewer patients reporting a grade 3 toxicity. There were no grade 4 or 5 toxicities,” Heseltine said.

There were no treatment-related deaths, but 18% of patients discontinued treatment due to toxicity.

“So, in summary, the key outcomes from our work is that the real-world data demonstrates a similar progression-free survival and overall survivor to the pivotal clinical trial, and that’s even with our population having a high proportion of poor-risk patients,” Heseltine said.

_Reference:

_{1. Heseltine J, Allison J, Wong S, et al. Tivozanib (T) as first-line (1L) treatment of metastatic renal cell carcinoma (mRCC): A real-world outcome review in North-West of England (NWE), UK. J Clin Oncol. 2022;40(suppl 6):335. doi:10.1200/JCO.2022.40.6_suppl.335}