The pivotal phase 3 KEYNOTE-426 trial investigating Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, in combination with Axitinib ( Inlyta ), tyrosine kinase inhibitor, met both primary endpoints of overall survival ( OS ) and progression-free survival ( PFS ) in the first-line treatment of advanced or metastatic renal cell carcinoma ( RCC ), the most common type of kidney cancer.
Based on the first interim analysis by the independent Data Monitoring Committee ( DMC ), the Pembrolizumab plus Axitinib combination resulted in statistically significant and clinically meaningful improvements in overall survival and progression-free survival, compared to Sunitinib ( Sutent ) monotherapy.
The study also met the key secondary endpoint of objective response rate ( ORR ), with significant improvements for the Pembrolizumab and Axitinib combination compared with Sunitinib monotherapy.
Results for OS, PFS and ORR were consistent regardless of PD-L1 expression and across all risk groups.
The safety profile of Pembrolizumab and Axitinib in this trial was generally consistent with that observed in previously reported studies for each therapy.
Pembrolizumab, in combination with the tyrosine kinase inhibitor Axitinib, 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.
Fewer than 10% of those diagnosed with advanced renal cell carcinoma survive for five years, and hence there is significant need for improved therapies for this disease.
KEYNOTE-426 is a randomized, double-arm, phase 3 trial evaluating the safety and efficacy of Pembrolizumab in combination with Axitinib as first-line treatment for advanced or metastatic RCC compared to Sunitinib.
The dual primary endpoints of the study were OS and PFS, and the key secondary endpoint was ORR. Additional secondary endpoints were disease control rate ( DCR ), number of participants who experienced or discontinued the study due to an adverse event, duration of response ( DOR ), PFS at 12, 18 and 24 months and OS at 12, 18 and 24 months.
In the trial, 861 patients were randomly assigned to receive Pembrolizumab 200 mg intravenously every three weeks plus Axitinib 5 mg orally twice daily for up to 24 months, or Sunitinib 50 mg orally once daily for four weeks followed by no treatment for two weeks, continuously.
Pembrolizumab is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Renal cell carcinoma is by far the most common type of kidney cancer; about 9 out of 10 kidney cancers are renal cell carcinomas. RCC is about twice as common in men as in women.
Modifiable risk factors include smoking, obesity, workplace exposure to certain substances and high blood pressure.
There are expected to be approximately 403,262 cases of kidney cancer diagnosed worldwide in 2018 and about 175,098 people will die from the disease.
In the U.S. alone, there will be an estimated 63,340 new cases of kidney cancer diagnosed in 2018 and about 14,970 people will die from the disease ( Xagena )
Source: Merck, 2018