The Food and Drug administration (FDA) in the USA has approved pembrolizumab for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate or high risk of recurrence following nephrectomy, or for RCC patients after having a nephrectomy and removal of metastases.
Adjuvant therapy is medication that is given in addition to surgery to try to prevent the cancer from coming back. Adjuvant therapy can be used to kill any remaining microscopic cancer cells, or it can control the growth of any remaining cancer.
Nephrectomy is the standard of care for RCC; however, the cancer can come back (recurrence) after nephrectomy. Adjuvant therapy would help to prevent recurrence of the disease in patients with intermediate or high risk RCC. Vascular endothelial growth factor (VEGF) inhibitors and cytokines have been tested as adjuvant therapies for RCC, but the benefit for patients has been inconsistent.
The phase 3 KEYNOTE-564 trial looked at the use of pembrolizumab as an adjuvant therapy for patients with clear cell RCC after nephrectomy. Patients were randomly allocated two separate groups with similar features and given either pembrolizumab or placebo for about one year.
Pembrolizumab significantly reduced the relative risk of the cancer returning by about one third (32%). After 2 years of treatment 77.3% of pembrolizumab patients remained disease-free compared to 68.1% on placebo. More follow up is required to make any definitive conclusions about overall survival, but it appears to favour pembrolizumab.
This is the first positive phase 3 study of adjuvant immunotherapy used for the treatment of intermediate to high risk RCC. There were no clinically meaningful changes from baseline in health-related quality of life or symptom scores for either pembrolizumab or placebo. This remained stable over time. Patient reported outcomes suggest that pembrolizumab was tolerable from a patient perspective.
Pembrolizumab is currently approved by several health authorities around the world for use in combination with axitinib as a first medication for patients with advanced RCC. Also, pembrolizumab is currently being assessed by the National Institute for Health and Care Excellence (NICE) for use within the NHS in England and Wales.