Seventy-three percent of patients with kidney cancer that appeared in other parts of their body after their main tumor had been removed responded to a combination of Inlyta (axitinib) and Keytruda (pembrolizumab), a Phase 1b clinical trial shows.
The combo shrank most patients’ metastatic tumors. It also prevented it from progressing for a median of 20.9 months — much longer than the 10-15 months that Inlyta alone had achieved in a similar situation, researchers said.
“Our results are unprecedented,” Dr. Michael B. Atkins, deputy director of the Georgetown Lombardi Comprehensive Cancer Center, said in a university news release. “The combination doubled the efficacy of the drugs when used alone, and the treatment was found to be tolerable,” said Atkins, the trial’s principal investigator.
Researchers presented the results at the ASCO Genitourinary Cancers Symposium in San Francisco, Feb. 8-10. The findings also appeared in a The Lancet Oncology article titled “Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial.”
Many cancers require the formation of new blood vessels to survive. Doctors have used anti-angiogenic agents to prevent their formation.
Although the agents have shown promise in kidney cancer, most patients’ disease has eventually progressed.
Immunotherapies have helped some patients whose kidney cancer worsened after anti-angiogenic therapies, however. Some of them target the PD-1 protein receptor that is associated with many cancers.
These findings prompted many scientists to believe that advanced kidney cancer patients might benefit from a combination of anti-angiogenesis agents and immune checkpoint inhibitors. When some of them tested the combination, however, it led to toxicity that patients were unable to tolerate.
In the Phase 1b clinical trial, researchers tested a combination of Inlyta, which inhibits blood vessel formation, and Keytruda. The U.S. Food and Drug Administration has approved Inlyta for advanced kidney cancer patients who fail to respond to other therapies, but few studies had looked at whether Keytruda could help them.
The trial (NCT02133742), sponsored by Pfizer and Merck, covered 52 kidney cancer patients.
In the first part, 11 patients received different doses of the combo for six weeks so researchers could identify the optimal dose they could tolerate. The team then tested the optimal dose in 41 patients.
The most common serious adverse events that patients experienced included high blood pressure, diarrhea, fatigue, and increased levels of the liver enzyme ALT. In general, patients tolerated the combo better than similar combinations, experiencing fewer liver abnormalities and less fatigue, researchers said.
After a median follow-up of 20.4 months, four patients had no traces of cancer, equating to a complete response. Thirty-four saw a reduction in the size of tumors that appeared outside their kidneys — a partial response. The treatment stabilized the cancer of eight patients.
Eighteen months after the therapy started, 88 percent of the patients were still alive.
“This trial shows that the combination of [Inlyta] and [Keytruda] is safe and tolerable” in advanced kidney cancer patients “and exhibits unprecented anti-tumour activity,” the researchers wrote.
“A randomized phase 3 trial [NCT02853331] comparing our drug combination to the FDA-approved anti-angiogenesis agent sunitinib is under way,” Atkins said. “It should tell us if this drug combination is better than the previous standard-of-care regimen. We think this combination could present a major advance in the treatment of this disease as well as help define effective combinations of similar drugs for other cancers.”
