Keytruda Combo Improves Survival in Advanced Renal Cell Carcinoma

The combination use of Keytruda (pembrolizumab) plus Inlyta (axitinib) significantly improved survival outcomes among patients with previously untreated advanced renal cell carcinoma (RCC), according to results from the KEYNOTE-426 trial published in The New England Journal of Medicine.

Moreover, the combination reduced the risk for death by 47% and disease progression by 31% compared to treatment with Sutent (sunitinib) — the standard first-line therapy for advanced RCC – the most common type of kidney cancer.

The researchers noted that, while agents like Sutent can be effective, more therapies are needed for this patient population. “Renal cell carcinoma is characterized by susceptibility to both immunotherapeutic and antiangiogenic treatment approaches and resistance to cytotoxic chemotherapy,” they wrote. “Despite the approval of several targeted therapies by entities such as the Food and Drug Administration, the European Medicines Agency and the Pharmaceuticals and Medical Devices Agency, the survival rate among patients with metastatic renal cell carcinoma has plateaued.”

Therefore, the researchers conducted the open-label, phase 3 KEYNOTE-426 trial to determine whether Keytruda in combination with Inlyta would produce better outcomes compared with Sutent in 861 patients with previously untreated advanced RCC.

Patients were randomized to receive either 200 mg of Keytruda intravenously once every three weeks plus 5 mg of oral Inlyta twice daily (432 patients) or 50 mg of oral Sutent once daily for the first four weeks of each six-week cycle (429 patients).

Overall survival and progression-free survival (the time from treatment to disease progression or worsening) served as the primary endpoint of the study, while objective response rate (the percentage of patients with tumor size reduction) was the secondary endpoint.

After a median follow-up of 12.8 months, the estimated percentage of patients who were alive at one year was 89.9% in the combination arm compared with 78.3% in the Sutent group, for a 47% reduced risk of death among the intent-to-treat population.

The combination arm also demonstrated median progression-free survival of 15.1 months compared with 11.1 months in the Sutent group, for a 31% reduced risk for progression. In addition, objective response rates were 59.3% and 35.7%, respectively.

The estimated percentage of patients with an ongoing response at one year was 70.6% in the combination group compared with 61.6% in the Sutent group.

The researchers noted the benefit found with Keytruda in combination with Inlyta was also observed across risk groups (favorable, intermediate and poor risk) and regardless of PD-L1 expression — a type of protein found on cancer cells that helps to determine treatment options.

In both groups, the most common side effects were diarrhea and hypertension. Grade 3 or higher side effects occurred in 75.8% of patients who received the combination regimen compared with 70.6% of those given Sutent.

“These data build on the single-agent activity of (Keytruda) and (Inlyta),” the researchers wrote. “The significant overall survival advantage is particularly notable because it has not been achieved with first-line treatment of renal cell carcinoma with the use of anti—VEGF-based therapy administered alone or in combination.”