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Results from the KEYNOTE-426 phase 3 study show that the combination of the PD-1 inhibitor pembrolizumab (Keytruder) and the VEGF inhibitor axitinib (Inlyta) significantly improves progression-free survival versus sunitinib (Sutent) as a first-line treatment for advanced or metastatic renal cell carcinoma (RCC).
A total of 861 untreated patients with advanced or metastatic RCC were randomly assigned to receive either sunitinib or the combination of pembrolizumab + axitinib for up to 24 months. Based on an interim analysis, there were statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared to sunitinib. There were also significant improvements in overall response rate for the combination compared with sunitinib. The results were independent of PD-L1 positivity and were seen across all risk groups.
The safety profile of pembrolizumab + axitinib was consistent with findings from previously reported studies.
“KEYTRUDA, in combination with the tyrosine kinase inhibitor Inlyta, resulted in significant and clinically meaningful improvements in overall survival, progression-free survival and objective response in this Phase 3 study. This marks the first time that combination treatment with an anti-PD-1 therapy has achieved the dual primary endpoints of overall survival and progression-free survival as first-line therapy in advanced renal cell carcinoma,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Fewer than 10 percent of those diagnosed with advanced renal cell carcinoma survive for five years, and hence there is significant need for improved therapies for this disease. We are very grateful to the investigators and patients for their involvement in this important study, the results of which will be filed with global regulatory authorities in the near future.”
In an earlier phase 1b dose-finding/dose-expansion study, 73% of patients (52 patients in total) had an objective response with the pembrolizumab + axitinib combination. Best overall response was a complete response in 4 patients (7.7%), partial response in 34 (65.4%), and stable disease in 8 (15.4%). The combination treatment significantly improved median progression-free survival (PFS) to 20.9 months, while overall survival was not reached.
In summary, these findings are very promising regarding the safety and efficacy of pembrolizumab + axitinib for patients with advanced RCC, and this study represents the first time that a combination treatment with a checkpoint inhibitor has improved both overall survival and progression-free survival as a first-line treatment for advanced RCC.