Fotivda Improves Survival in Relapsed, Refractory Metastatic Renal Cell Carcinoma

Fotivda (tivozanib) significantly improved survival, compared with Nexavar (sorafenib), in patients with highly relapsed or refractory metastatic renal cell carcinoma (RCC), according to results from the phase 3 TIVO-3 trial presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

“We believe the TIVO-3 data demonstrate a favorable risk/benefit profile for tivozanib in the growing population of patients who have relapsed or become refractory to multiple lines of therapy, including checkpoint inhibitors,” Dr. Sumanta Pal, associate clinical professor in the Department of Medical Oncology and Therapeutics Research and co-director of the Kidney Cancer Program at City of Hope Comprehensive Cancer Center, said in a press release.

An updated analysis of the data found that with a median follow-up of 38 months for Fotivda and 40 months for Nexavar, median overall survival was 16.4 months and 19.2 months, respectively. A subset analysis showed the greatest benefit was derived by the cohort of patients that had received treatment with a prior checkpoint inhibitor and VEGF inhibitor.

Previously released data also showed an increased median progression-free survival (the time from treatment to disease worsening) for Fotivda when compared with Nexavar.

“The lack of clinical data to guide treatment decisions in a robust, evidence-based manner in this setting is a serious and growing unmet medical need, particularly as this population continues to grow thanks to improved treatment in earlier lines,” Pal added. “TIVO-3 provides the first positive superiority study to help guide this important treatment decision and, furthermore, offers this highly refractory patient population a favorable tolerability profile as indicated by fewer dose reductions, interruptions and discontinuations over a less selective VEGFR TKI in sorafenib.”

The TIVO-3 study was a controlled, multicenter, open-label, phase III trial which randomized 350 patients with highly refractory metastatic RCC who had failed two or more prior regimens, including VEGF-TKI treatment, 1:1 to receive either oral Fotivda or Fotivda. Crossover between arms was not permitted.

Eighteen percent of patients in the Fotivda arm achieved partial response, compared with 8% of those in the Fotivda arm. The objective response rate was 34% and 24%, respectively.

Treatment with Fotivda was found to be generally well-tolerated, and the safety profile was favorable when compared with Nexavar. Treatment-related side effects were reported in 84% of patients receiving Fotivda and 94 of those receiving Nexavar. Serious treatment-related side effects occurred in 11% of patients treated with Fotivda versus 10% of patients who received Nexavar.

The most common grade 3 or 4 side effects reported in patients receiving Fotivda and Nexavar was hypertension (21% vs 14%, respectively). The most commonly reported any grade side effects associated with Fotivda were hypertension (38%), diarrhea (33%), fatigue (29%) and decreased appetite (27%).

The investigators reported significantly reduced dose reductions and interruptions due to side effects for Fotivda versus Nexavar (48% vs 63%), despite nearly double the average time of cycles initiated for the tivozanib arm (11.9 months vs 6.7 months, respectively). Treatment related side effects leading to permanent discontinuation were 8% for Fotivda compared with 15% for Nexavar.

“The biggest advantage to tivozanib is tolerability,” Dr. Brian Rini, from Vanderbilt-Ingram Cancer Center, said in a recent interview with CURE “One thing where my mindset has changed now that we have immune therapy combinations that can be curative, is that when we are using single agent TKIs, we’re really just trying to control disease. Because we’re not curing those patients, and they can be on (TKI therapy) for many months or years, tolerability is really the key thing.”

Rini added that these findings support the use of another VEGF TKI in this patient population. “Patients, appropriately, always want more options,” he said. “…Having tolerable options, especially in this late line setting, is a potential advantage to patients. I often describe to patients that we’re just trying to get as many shots on goal as possible…So, I think it adds to our weapons in this disease.”