Advanced Refractory RCC: TIVO-3 Results Presented for Tivozanib vs Sorafenib

The vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor tivozanib led to better progression-free survival (PFS) compared with sorafenib across multiple subgroups of refractory advanced renal cell carcinoma (RCC). This result comes from the TIVO-3 trial, which was conducted in 350 patients who had previously received two or three systemic therapies. The study data was presented (abstract 4572) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.

Tivozanib is approved for first-line treatment of renal cell carcinoma in Europe, but has not been approved by the US Food and Drug Administration. In TIVO-1, the first-line therapy, phase III trial, the drug delivered better progression-free survival and overall response rate than sorafenib. The TIVO-3 study examined tivozanib’s potential as a third- and fourth-line therapy in metastatic RCC.

To be eligible for the trial, patients needed to have received previous treatment with a VEGF receptor tyrosine kinase inhibitor other than tivozanib or sorafenib. Overall median progression-free survival (PFS) was 5.6 months with tivozanib vs 3.9 months for sorafenib (hazard ratio [HR], 0.73; P = .017). The benefit of tivozanib was maintained in all subgroups, including men (HR, 0.64), women (HR, 0.72), age ≤ 65 years (HR, 0.74), and age > 65 years (HR, 0.59). There was no difference in benefit between patients who were recruited from the United States vs from the European Union.

The benefit was greater in patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 than those with an ECOG performance status of 1 (HR, 0.54 vs 0.87, respectively). The benefit decreased from International Metastatic RCC Database Consortium (IMDC) favorable, to IMDC intermediate, to IMDC poor (HR, 0.46 vs 0.69 vs 1.15).

Still, the treatment was effective in subgroups with a worse prognosis: PFS was better with tivozanib in subjects who received treatment with two previous VEGF tyrosine kinase inhibitor therapies (HR, 0.58), patients who had previously received a checkpoint inhibitor (HR, 0.55), and third-line (HR, 0.69) and fourth-line (HR, 0.65) patients.

“The study showed you got longer progression-free survival than sorafenib, and particularly for good-risk and intermediate-risk patients. The poor-risk patients looked like they did worse. This, in theory, would be an argument for patients who progressed on first-line tyrosine kinase inhibitors and then progressed on immunotherapy, or may on other combinations – this would then be a valid choice to go to,” Tim Gilligan, MD, associate professor and vice chair for education at the Cleveland Clinic Taussig Cancer Institute, told Cancer Network.