The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), based in Amsterdam, The Netherlands, has adopted a positive opinion recommending approval of pembrolizumab als known as MK-3475 (Keytruda®; Merck/MSD), a anti-PD-1 therapy, in combination with axitinib (Inlyta®; Pfizer Oncology), a tyrosine kinase inhibitor, for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
Renal cell carcinoma (RCC) is by far the most common type of kidney cancer. About 9 out of 10 kidney cancers are diagnosed as renal cell carcinomas. This disease 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 were approximately 403,000 cases of kidney cancer diagnosed worldwide in 2018 and about 175,000 deaths from the disease. In Europe, it is estimated that 136,500 new cases of kidney cancer were diagnosed in 2018 and approximately 54,700 people died from the disease.
Novel treatment combination
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.
This recommendation, which applies to all International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups, is based on findings from the pivotal Phase III KEYNOTE-426 trial (NCT02853331), which demonstrated significant improvements in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) for pembrolizumab in combination with axitinib compared to sunitinib.
The trial results confirmed, that after a median follow-up of 12.8 months, the estimated percentage of patients who were alive at 12 months was 89.9% in the pembrolizumab-axitinib group and 78.3% in the sunitinib group (hazard ratio for death, 0.53; 95% confidence interval [CI], 0.38 to 0.74; P<0.0001).
The study resuts also demonstrated a median progression-free survival of 15.1 months in the pembrolizumab-axitinib group and 11.1 months in the sunitinib group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.57 to 0.84; P<0.001). And, finally, the objective response rate (ORR) was 59.3% (95% CI, 54.5 to 63.9) in the pembrolizumab-axitinib group and 35.7% (95% CI, 31.1 to 40.4) in the sunitinib group (P<0.001).
Clinical trial program
Merck has one of the largest immuno-oncology clinical research program with more than 1,000 trials studying pembrolizumab across a wide variety of cancers and treatment settings. This clinical program seeks to understand the role of pembrolizumab across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with pembrolizumab, including exploring several different biomarkers.
“For patients with advanced renal cell carcinoma, the prognosis is poor, with a five-year survival rate of less than 10%,” said Dr. Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories.
“The positive opinion adopted by the EMA, which is based on data showing pembrolizumab 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,” Ebbinghaus added.
The data from the KEYNOTE-426 trial were presented for the first time at the 2019 Genitourinary Cancers Symposium, ASCO GU, organized by the American Society of Clinical Oncology and published in The New England Journal of Medicine.
The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the third quarter of 2019.
Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma (MK-3475-426/KEYNOTE-426) | NCT02853331
 Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1116-1127. doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16. [Pubmed][Article]