The treatment of metastatic renal cell carcinoma (RCC) has evolved over the last ten years and investigators now look towards combination therapies to improve response rates and durability for patients.
This is evidenced by the encouraging results of Phase 3 KEYNOTE-426 trial announced by Merck and published recently in the New England Journal of Medicine.
Dr. Roger M. Permutter, the president of Merck Research Laboratories, commented that this is the first time that combination treatment with anti-PD-1 therapy has met the primary endpoints of both progression-free survival and overall survival in advanced renal cell carcinoma. Anti-PD-1 antibodies, by way of T cells, activate the immune response against the tumor.
Dr. Permutter emphasized the urgency of improving this therapy as fewer than ten percent of patients diagnosed with the disease survive more than five years.
About the Phase III KEYNOTE-426 Trial
KEYNOTE-426 evaluated the safety and efficacy of Keytruda (pembrolizumab) in combination with Pfizer’s Inlyta® (axitinib), a tyrosine kinase (enzyme) inhibitor that targets these enzymes which are responsible for the activation of many proteins. The two drugs, in combination, were compared against sunitinib monotherapy.
The Phase III trial was an open-label, randomized study with 862 participants who had not had prior treatment. Details of the trial are available here.
About Renal Cell Carcinoma (RCC)
Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes (tubules) in the kidney.
Nine out of ten kidney cancers are renal cell carcinomas. Men between the ages of 50 to 70 are most often affected. Some possible RCC risk factors are obesity, high blood pressure, exposure to certain substances at the workplace, and smoking. However, the exact cause is unknown.
The symptoms may include back pain, blood in the urine, weight loss, fever, abdominal pain and swelling, and liver dysfunction. Additional information about RCC is available here.
About Keytruda ® (pembrolizumab)
Keytruda is an anti-PD-1 therapy that activates the immune system’s ability to detect and fight tumor cells. It is a monoclonal antibody that blocks the interaction between PD-1 and its ligands (molecules) thus activating T lymphocytes (a subtype of white blood cells).
There are approximately 850 trials studying Keytruda in relation to a wide variety of cancers.
About Inlyta® (axitinib)
Inlyta, a targeted therapy, is an oral tyrosine kinase inhibitor that exerts an anti-angiogenic effect by inhibiting the growth of new blood vessels. The new blood vessels are critical for the continued growth and survival of cancer tumors.
Sunitinib, marketed as Sutenet by Pfizer, is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) in 2006 for locally advanced or metastatic renal cell carcinoma (mRCC).
By targeting multiple receptor tyrosine kinases (RTKs), Sunitinib inhibits cellular signaling. The simultaneous inhibition of these targets triggers cancer cell apoptosis (cell death) and thus results in tumor shrinkage. The fact that sunitinib targets many different receptors leads to its side effects.
The study met the primary endpoints with significantly longer progression free survival and overall survival as well as the secondary endpoint of objective response rate (ORR).
According to findings from the phase III KEYNOTE-426 study, significant improvements were achieved for the Keytruda and Inlyta combination when compared with sunitinib monotherapy in treatment-naive patients with clear cell metastatic renal cell carcinoma.
The FDA granted a priority review designation to a supplemental biologics license application covering the combination of pembrolizumab and axitinib for patients with advanced RCC in February 2019. The priority review moves the FDA’s time frame to take action from ten months to six months.