The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Treatment of heavily pretreated renal cell carcinoma (RCC) with tivozanib prolonged progression-free survival (PFS), but not overall survival (OS), compared with sorafenib, according to the final OS analysis of the phase 3 TIVO-3 trial. These findings were presented at the ASCO20 Virtual Scientific Program.

“There’s very little evidence that exists to guide treatment decisions in later lines of therapy, especially for patients with relapsed or refractory metastatic RCC who have received prior checkpoint inhibitors,” said Sumanta K. Pal, MD, of City of Hope in Duarte, California, and lead author and presenter.

The primary results of the TIVO-3 trial were published previously, in which tivozanib met its primary endpoint of PFS. This presentation is of the final OS analysis.

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The phase 3 TIVO-3 trial randomly assigned 350 patients with RCC that progressed after 2 or more therapies, including a VEGF inhibitor, to receive tivozanib or sorafenib. Patients were stratified by risk category and prior regimen. The primary endpoint was PFS and secondary endpoints included OS, objective response rate (ORR), duration of response (DOR), and safety.

Baseline demographics of patients were well-balanced, with a median age of 63 and 73% were male. Most patients were categorized as intermediate risk (61%), with the remaining categorized as favorable (20%) or poor (19%). There were 61% of patients who had received 2 prior lines of therapy and 40% who had received 3 prior lines.

Tivozanib significantly prolonged PFS, with a median of 5.6 months (95% CI, 5.3-7.3 months) compared with 3.9 months (95% CI, 3.7-5.6 months) with sorafenib (hazard ratio [HR], 0.73; 95% CI, 0.56-0.94; P =.016). The 2-year PFS was 18% with tivozanib compared with 5% with sorafenib.

“The greatest benefit, as demonstrated by a prespecified analysis of subgroups, appeared to be in the cohort of patients that had received prior checkpoint inhibitor and VEGF inhibitor with a hazard ratio of 0.55, or 2 VEGF TKIs with a hazard ratio 0.57,” Dr Pal said.

OS was similar between arms, with a median of 16.4 months and 19.2 months in the tivozanib and sorafenib arms, respectively (HR, 0.97; 95% CI, 0.75-1.24; P =.78). Final OS is pending confirmation.

ORR was also higher with tivozanib, at 18% compared with 8% in the sorafenib arm (P =.02). In the subgroup analysis, the ORR was higher with tivozanib (24%) compared with sorafenib (6.8%) among patients who had received a prior ICI and VEGF TKI. The disease control rate was 73% and 65% in the tivozanib and sorafenib arms, respectively.

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Grade 3/4 treatment-related adverse events occurred more frequently in the sorafenib arm (55%) compared with the tivozanib arm (46%). However, grade 3/4 hypertension occurred more frequently in the tivozanib arm.

“In summary, tivozanib significantly improved PFS and response rates with similar OS and improved tolerability to sorafenib in patients with highly treatment-refractory advanced RCC across several patient subgroups,” Dr Pal said.

Research funding for this study was provided by AVEO Oncology.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). Presented at: ASCO 20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 5062.