Retrospective trial outcomes inform utility of tivozanib within the real-world remedy of renal cell carcinoma.
Information offered on the 2022 Genitourinary Cancers Symposium present noninferiority of frontline tivozanib (Fotivda) vs different tyrosine kinase inhibitors as a real-world remedy possibility for sufferers with metastatic renal cell carcinoma (mRCC).
In line with research creator Jonathan Heseltine, MBChB, of the Clatterbridge Most cancers Centre within the UK, the agent’s tolerable security profile makes it a pretty possibility for this affected person inhabitants.
“We got down to consider the real-world use of tivozanib as a result of we had some indicators that this is perhaps the popular drug due to the toxicity profile. So, we gathered information throughout our 3 separate regional most cancers facilities from March 2017 to 2019 and checked out these outcomes,” stated Heseltine in a presentation of the findings.
The retrospective trial concerned 113 sufferers with mRCC–82% (n = 93) with a confirmed clear cell histology, and 18% (n = 20) undefined. About half of the sufferers (52%; n = 59) had been decided to be an intermediate prognosis per Worldwide Metastatic RCC Database Consortium (IMDC) requirements. Twenty-two p.c (n = 25) had favorable prognosis, and 26% (n = 29) had poor prognosis. Sixty-six p.c (n = 75) had undergone a earlier nephrectomy.
At a median follow-up of 25.9 months (vary, 18.3-44.7 months), the general response charge (ORR) was 29%. There have been no full responses, and 29% of sufferers skilled partial response, 39% secure illness, 26% progressive illness, and 6% of sufferers weren’t evaluable.
Of notice, 88.5% of sufferers began tivozanib on the full dose, with 67% sustaining dose depth; 11.5% began remedy with a dose discount due to prior TKI-related toxicities or comorbidities. Median variety of cycles was 7 (vary, 1-33).
Median progression-free survival (PFS) was 9.0 months (95% CI, 6.0-12.1 months; P <.0001), however different amongst IMDC danger teams:
- 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 three.0 months (95% CI, 1.5-4.5)
All-grade antagonistic occasions (AEs) had been skilled in 77% of sufferers, with 14% being grade 3. Widespread AEs had been: 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 fascinating discovering, contemplating that the TIVO-1 medical trial of tivozanib had a big proportion of sufferers with critical grade 3 or low-level hypertension or dysphonia, which was not seen within the non-trial setting, Heseltine stated.
The researchers talked about that notable grade 3 occasions included irregular liver perform (3%), vascular occasions (2%), and seizure (<1%).
“The protection information was fascinating in that we discovered that there have been fewer sufferers reporting a grade 3 toxicity. There have been no grade 4 or 5 toxicities,” Heseltine stated.
There have been no treatment-related deaths, however 18% of sufferers discontinued remedy attributable to toxicity.
“In abstract, the important thing outcomes from our work is that the real-world information demonstrates the same progression-free survival and total survivor to the pivotal medical trial, and that’s even with our inhabitants having a excessive proportion of poor-risk sufferers,” Heseltine stated.
Heseltine J, Allison J, Wong S, et al. Tivozanib (T) as first-line (1L) remedy of metastatic renal cell carcinoma (mRCC): An actual-world consequence evaluation in North-West of England (NWE), UK. J Clin Oncol. 2022;40(suppl 6):335. doi: 10.1200/JCO.2022.40.6_suppl.335