Nephrectomy is the standard of care for advanced renal cell carcinoma (RCC); however, the cancer can come back (recurrence) after nephrectomy. Adjuvant therapy is medication that is given after surgery to try to prevent the cancer from coming back.

In the past, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs) 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 to two separate groups with similar features and given either pembrolizumab or placebo for about one year. During and after treatment patients were monitored for return of their cancer.

Previously reported data showed that treatment with adjuvant pembrolizumab significantly reduced the relative risk of the cancer returning by about one third (32%) after 2 years. Treatment with adjuvant pembrolizumab resulted in over 78% of patients remaining disease free compared to 67% with placebo after 2 years. This means that one third of patients on placebo were at risk of their cancer returning after surgery. A further 6 months of follow-up data were presented at ASCO GU 2022.

This survival benefit was maintained during the extra 6 months of follow-up for patients at intermediate to high risk of recurrence, although it is still too early to see a benefit in overall survival time. Also, the number of patients experiencing side effects to pembrolizumab remained unchanged compared with patients on placebo (91.3%). Serious or life-threatening side effects were also very similar for patients taking pembrolizumab at 2 years and 2.5 years (8.6% versus 8.8%, respectively) compared with 0.6% for patients on placebo at both time points

A poster presentation looked at the quality of life of the patients on the KEYNOTE-564 trial. There was only a minor deterioration of quality of life for patients treated with pembrolizumab compared to placebo, which the researchers did not consider statistically significant. Importantly, quality of life remained stable over time. Patients reported that pembrolizumab was tolerable from a patient perspective.

This updated analysis of KEYNOTE-564 further supports the use of adjuvant pembrolizumab as a new standard of care for patients with RCC with high risk of recurrence.

When prescribing adjuvant pembrolizumab, clinicians should consider each individual patient’s treatment benefit and risk based on available clinical evidence. Not all patients are the same, and there is no biomarker to predict disease recurrence. Since overall survival data are not yet available, clinicians should take this into account when discussing adjuvant pembrolizumab with patients. Also, without biomarkers to predict which patients will respond to treatment or succumb to serious side effects, over treatment is likely to occur, particularly in those patients who are disease free after surgery.

Clinicians should take special care to inform patients about the potentially serious side effects of pembrolizumab, particularly since the quality-of-life questionnaires do not capture chronic side effects and these patients are free from cancer symptoms at the start of adjuvant treatment. Potential serious side effects of pembrolizumab must be considered carefully.

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