Experimental Targeted Therapy Pill Extends Lives of Patients with Metastatic Renal Cell Carcinoma

When John Floyd received a stage 4 renal cell carcinoma (RCC) diagnosis, he had surgery to remove his right kidney and then tried different chemotherapy medications. When those therapies didn’t work, Floyd sought a second opinion at City of Hope in Duarte, California.

Experts there suggested he enroll in a phase 3 clinical trial that was investigating an experimental targeted therapy in patients with kidney cancer who have already tried two or three different treatments — patients just like Floyd.

In the trial, more than 300 patients with metastatic RCC were randomly chosen to receive Fotivda (tivozanib) or Nexavar (sorafenib) for a median of 19 months. While Nexavar is already approved by the Food and Drug Administration (FDA), Fotivda, an oral VEGFR inhibitor that stops the growth of new blood vessels that fuel tumors, is not.

The patients, who were a median age of 63, were recruited from more than 120 centers in 12 different countries. Treatment began in May 2016.

At one year, progression-free survival (PFS), or the time a patient’s disease does not worsen, was 28% with Fotivda compared with 11% treated with Nexavar. Fotivda also improved PFS at two years, with 18% of patients not worsening compared with 5% in the Nexavar group. “The therapeutic benefit of tivozanib appeared to extend to patients who had received checkpoint inhibitors and those who were treated with two previous blood vessel growth inhibitors,” according to a press release.

Floyd is one of those patients. The 76-year-old was chosen to be part of the Fotivda group and has been on the experimental medication for nearly four years. It has stopped the spread of his cancer.

“I was really happy to be asked to participate in the clinical trial because I had already undergone treatment with three different forms of chemotherapy and all of them were failures,” Floyd said in an interview with CURE®. “I looked at it as an opportunity to try something different. There was some reluctance initially, but then when I thought about it there really wasn’t any other choice to make.”

RCC is the most common form of kidney cancer. It affects more than 70,000 people in the United States each year, more often men than women.

At the study’s end, 70 patients (40%) in the Fotivda group and 82 patients (47%) in the Nexavar group saw their disease progress, according to findings published in The Lancet Oncology.

“This agent has shown in clinical trials to be effective in delaying cancer growth beyond established standards for patients who have returning kidney cancer,” said Dr. Sumanta Pal, a medical oncologist at City of Hope and co-lead author of the study. “Although there are many options for patients with kidney cancer today, most are intended for first- and second-line therapy. We need a treatment that works for kidney cancer patients who have failed several lines of therapy.”

The most common treatment-related side effects were hypertension (20% of patients treated with Fotivda and 14% of patients treated with Nexavar). Serious treatment-related side effects were seen in 11% of patients in the Fotivda group and 10% in the Nexavar group.

The medication has stopped Floyd’s chronic cough and the blood that would come up with it. However, during the middle of his treatment cycle — he is on the pill for 21 days, then off for a week — Floyd experiences nausea and loss of appetite, loss of energy and diarrhea.

“It’s a small price to pay when the cancer has remained static in the 44 months that I’ve been taking (the medication),” Floyd said.

Aveo Oncology, the maker of Fotivda, plans to submit a new drug application to the FDA in early 2020 to hopefully lead to an approval that will allow this pill to be used by patients who have stopped responding to treatment or whose disease has progressed.