The Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency (EMA), has recommended that a combination of Keytruda (pembrolizumab) and Inlyta (axitinib) be approved as a first-line treatment for advanced renal cell carcinoma, the most common type of kidney cancer.
The European Commission is now reviewing CHMP’s recommendation and will decide if the combination therapy will be approved for use in the European Union. A final decision is expected by September.
Keytruda is an immune checkpoint inhibitor developed by Merck (known as MSD outside the U.S. and Canada) designed to bind the PD-1 protein on immune T-cells and impede cancer cells’ ability to escape immune surveillance.
Inlyta, developed by Pfizer, is an inhibitor of tyrosine kinases, which are proteins involved in tumor growth and blood vessel formation. By inhibiting these proteins, Inlyta reduces the oxygen and nutrient supplies that reach tumors, halting their proliferation, and promoting their death.
The CHMP’s recommendation was based on findings from the pivotal KEYNOTE-426 Phase 3 trial (NCT02853331), in which the Keytruda-Inlyta combination extended patients’ overall survival, delayed disease progression or death, and increased rates of responses to treatment.
The study enrolled 861 people with metastatic renal cell carcinoma who had not received prior treatment for their advanced disease. They were assigned randomly a combination of Keytruda with Inlyta, or the standard treatment Sutent (sunitinib).
Treatment was continued until patients experienced disease progression, showed signs of unacceptable toxicity, or dropped out of the study.
While more than half of the patients in each group were alive at the time of the analysis, researchers estimated the one-year overall survival rates were 90% for the combination group, and 78% for the Sutent-treated group.
Patients who were treated with the combination lived a median of 15.1 months without signs of disease worsening, which was significantly longer than the 11.1 months reported for Sutent. This meant that the combination cut the risk of death by 47%, and the risk of disease worsening by 31% compared with Sutent.
The proportion of patients experiencing severe adverse side effects was similar in both groups — 62.9% for the combination vs. 58.1% for Sutent. However, more patients on Sutent discontinued treatment due to severe side effects — 6.3% vs. 10.1%.
“For patients with advanced renal cell carcinoma, the prognosis is poor, with a five-year survival rate of less than 10%,” Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, said in a press release.
“The positive opinion adopted by the EMA, which is based on data showing Keytruda in combination with axitinib significantly improved overall survival regardless of PD-L1 expression, is an important step toward a new first-line treatment option for these patients,” he said.
In April, the U.S. Food and Drug administration approved this combination for a similar indication.