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 renal cell carcinoma; however, the cancer can come back (recurrence) after nephrectomy. Adjuvant therapy would help to prevent recurrence of the disease in patients with locally advanced 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.
Quality of life using patient reported outcomes were assessed in all patients who had been treated with at least one dose of pembrolizumab or placebo. Quality of life was assessed at before infusion 1, 5, 9, 13 and 17, when treatment was stopped, 30 days after the last dose of treatment, and annually thereafter until recurrence of the cancer or the start of new treatment.
Of the 496 patients on pembrolizumab and 498 patients on placebo, more than 90% completed the baseline quality of life questionnaires and more the 60% completed them at 1 year.
This is the first positive phase 3 study of adjuvant immunotherapy used for the treatment of locally advanced 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. However, pembrolizumab is yet to be approved dur to the lack of mature overall survival data. These quality-of-life data show promise for pembrolizumab as the new standard of care for the adjuvant treatment of RCC.