The phase 3 TIVO-3 trial – designed to evaluate the efficacy of Fotivda in patients with renal cell carcinoma – met its primary endpoint of improved progression-free survival.
Patients with renal cell carcinoma who were treated with Fotivda (tivozanib) experienced a 26 percent reduction in the risk of progression or death compared with Nexavar (sorafenib), according to positive results from the phase 3 TIVO-3 trial.
Further, AVEO Oncology — the agent’s manufacturer – noted these are the first and only positive phase 3 study results in the third- and fourth-line setting of renal cell carcinoma.
“In the advanced disease setting, these outcomes are particularly meaningful, providing the first large, pivotal dataset that shows sequencing of treatment following earlier TKI and immunotherapy treatment,” principal investigator Brian Rini, M.D., director of the Cleveland Clinic’s Genitourinary Cancer Program, said in a press release.
“This profile suggests an important place for tivozanib in the evolving treatment paradigm for RCC and, taken together with early combination data, the need to study tivozanib further in combination with immunotherapies,” he added.
The TIVO-3 trial compared the efficacy of Fotivda with Nexavar in 351 patients with renal cell carcinoma who failed at least two prior regimens, including VEGFR-TKI therapy. Progression-free survival, or the time to disease progression or worsening, served as the primary endpoint, while secondary endpoints included overall survival, overall response rate, and safety and tolerability.
The agent demonstrated a 44 percent improvement in median progression-free survival and a 26 percent reduction in the risk of progression or death, with a median advantage of 5.6 months in the Fotivda arm compared with 3.9 months in the Nexavar arm.
Among the 26 percent of patients who previously received checkpoint inhibitor therapy in earlier lines of treatment, progression-free survival was still longer with Fotivda than Nexavar.
Overall survival analysis was not mature at the time of the final progression-free survival analysis, as only 46 percent of overall survival events have been reported. AVEO Oncology noted final survival analysis per protocol is planned for August 2019 — two years following the last patient enrolled.
The safety profile of Fotivda appeared consistent with previous studies. The most common side effect with the agent was hypertension, which is known to reflect effective VEGF pathway inhibition, the manufacturer explained.
AVEO Oncology intends to submit a new drug application to the Food and Drug Administration (FDA), and in the meantime, expressed its gratitude toward what has been a long fight: “Our determination to fight for tivozanib in 2015, when AVEO faced an important strategic crossroads, came from our belief that it could have a meaningful impact not just on how a disease was treated, but also what the patient experiences through that treatment,” said Michael Bailey, president and chief executive officer of AVEO Oncology.
“(The trial’s) outcome is the culmination of that multi-year effort, and a first step in our goal to improve both outcomes and patient experience,” he added. “We owe our deepest gratitude to the health care professionals, many of whom long believed in the potential of tivozanib, and to the patients and their families for participating in our pivotal studies.”