Tivozanib outdoes sorafenib in RCC in TIVO-3
The biochemically potent, highly selective VEGFR TKI* tivozanib trumped sorafenib in improving progression-free survival (PFS) and objective response rate (ORR) in patients with refractory advanced renal cell carcinoma (RCC), according to results of the TIVO-3** study presented at ASCO GU 2019.
This multinational phase III trial comprised 350 participants (median age 63 years, 73 percent male) with advanced clear cell RCC who failed prior systemic regimens (about 50 percent received two prior TKIs while 25 percent received checkpoint inhibitors). Participants were randomized 1:1 to receive either tivozanib 1.5 mg once daily (3 weeks on/1 week off per cycle) or sorafenib 400 mg twice daily (continuously in 4-week cycles). Treatment ran until progression or unacceptable toxicity. [ASCO GU 2019, abstract 541]
Tivozanib recipients showed better objective response rates (ORR) than sorafenib-treated patients (18 percent vs 8 percent; p=0.02).
PFS rates were higher with tivozanib than sorafenib at 1 year (28 percent vs 11 percent) and 2 years (18 percent vs 5 percent), translating to a significantly better PFS (median, 5.6 vs 3.9 months, hazard ratio [HR], 0.73, 95 percent confidence interval [CI], 0.56–0.94; p=0.02).
“[T]he durability of responses with tivozanib were … quite impressive,” said Prof Brian Rini from the Cleveland Clinic Taussig Cancer Institute in Cleveland, Ohio, US, in a separate interview, given the number of patients who were still progression-free at 2 years.
These results validate the findings in TIVO-1*** which also showed superior PFS (11.9 vs 9.1 months; HR, 0.80; p=0.04) and ORR (33 percent vs 23 percent) with tivozanib vs sorafenib.
All-grade treatment-related AE rates were lower among tivozanib vs sorafenib recipients (84 percent vs 94 percent), the most common being hypertension, diarrhoea, and fatigue. Tivozanib recipients were also less likely to require dose reduction (24 percent vs 38 percent), interruption (48 percent vs 63 percent), or discontinuation (21 percent vs 29 percent) due to an AE.
“[T]ivozanib is a well-tolerated drug … probably the best tolerated TKI owing in part to its selectivity for the VEGF receptor,” said Rini. Sorafenib was associated with more bothersome, “off-target” toxicities (ie, hand-foot syndrome, rash) as opposed to the “on-target” toxicities (ie, hypertension, fatigue) associated with tivozanib.
While the interim overall survival (OS) rate favoured sorafenib over tivozanib (19.7 vs 16.4 months, HR, 1.12, 95 percent CI, 0.84–1.51; p=0.44), the findings highlighted the PFS advantage of tivozanib over sorafenib in a very refractory, heavily VEGF-pretreated population, noted Rini.