Fotivda Nearly Doubles Duration of Response Compared With Nexavar in Metastatic Kidney Cancer

Patients with metastatic renal cell carcinoma treated with Fotivda (tivozanib) had a significantly greater duration of response compared with Nexavar (sorafenib), according to long-term data from a phase 3 trial.

“Collectively, these data confirm and extend previous findings for (Fotivda) as an evidence-based treatment option for patients with relapsed and refractory (renal cell carcinoma) including for patients whose disease has progressed after previous checkpoint inhibitor therapy,” the study authors concluded in the poster presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

At the data cutoff for these analyses (January 15, 2021), the agent demonstrated clinically meaningful and statistically significant improvements in overall response rates and duration of response, with similar overall survival, compared with Nexavar.

Per investigator assessment, 41 (23%) patients in the Fotivda group experienced a response to treatment compared with 20 (11%) patients in the Nexavar group. Similarly, the Fotivda group had a superior disease control rate compared with the Nexavar group (82% vs 69%, respectively), as well as a better partial response rate (23% vs 11%) and stable disease rate (59% vs 58%).

Median duration of response was 20.3 months with the potent and highly selective vascular endothelial cell growth factor tyrosine kinase inhibitor Fotivda, compared with 9 months with Nexavar. Moreover, 13 (7%) patients treated with Fotivda had continued ongoing responses at the time of data cutoff — 32% of the response group — compared with 3 (2%) patients treated with Nexavar.

With the prolonged follow-up, Fotivda demonstrated superior overall survival compared with Nexavar; however, this did not reach statistical significance.

“(A) statistically significant improvement in (progression-free survival) and (overall response rates) had previously been shown and continues to improve with longer follow-up,” the study authors wrote. “(Overall survival) relative to (Nexavar) continues to improve with longer follow-up.”

In the open-label, randomized-controlled phase 3 trial, investigators compared the efficacy and safety of Fotivda with Nexavar as a third- or fourth-line therapy in patients with metastatic renal cell carcinoma. In a poster presentation at the ASCO annual meeting, the study authors reported on the long-term durability of response based on an investigator assessment and updated overall survival in patients from the trial.

Between May 24, 2016, and August 14, 2017, investigators assigned patients to receive treatment with either Fotivda at 1.5 mg orally once daily for three weeks on and one week off in four-week cycles (175 patients) or Nexavar at 400 mg orally twice daily continuously in four-week cycles (175 patients) until progression or unacceptable toxicity.

To be eligible for the trial, patients had to have advanced clear cell metastatic renal cell carcinoma and progressed on two or three prior systemic therapies including one or more vascular endothelial cell growth factor tyrosine kinase inhibitors.

A major focus of this study was to assess progression-free survival, overall survival, overall response rates, duration of response and safety. Follow-up was conducted for a median of 19 months.

Patients treated with Fotivda were a median age of 62 years. Most patients in the Fotivda group were men (72%), had intermediate-risk disease (62%) and received two prior systemic therapies (62%) including two vascular endothelial cell growth factor tyrosine kinase inhibitors (45%).

The trial, which was originally published in Lancet Oncology in early 2020, showed that median progression-free survival was significantly longer in the Fotivda group compared with the Nexavar group (5.6 months versus 3.9 months). In addition, overall response rates were 18% versus 8%.

The most common severe or life-threatening treatment-related side effects in the Fotivda and Nexavar groups was high blood pressure (20% vs 14%, respectively). Serious treatment-related side effects occurred in 19 (11%) patients treated with Fotivda and in 17 (10%) patients treated with Nexavar. No treatment-related deaths were reported.

As a result of the initial study findings, in March 2021, the Food and Drug Administration approved Fotivda for adult patients with relapsed or refractory advanced renal cell carcinoma following two or more prior systemic therapies.

“(Fotivda) is a potent and highly selective (vascular endothelial cell growth factor) tyrosine kinase inhibitor with a long half-life that is an effective treatment option for patients with previously treated (metastatic renal cell carcinoma),” the study authors wrote, adding that the agent is approved in the EU for patients who are not previously treated with a vascular endothelial cell growth factor tyrosine kinase inhibitor or mTOR inhibitor.

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