Pembrolizumab Becomes First Adjuvant Treatment to Improve Renal Cell Carcinoma Survival

The researchers were conducting the third prespecified interim analysis of KEYNOTE-564, a phase III, double-blind, placebo-controlled trial in which they randomly assigned 1:1 participants with clear-cell renal cell carcinoma who had an increased risk of recurrence after surgery to receive 200 mg pembrolizumab (n = 496) or placebo (n = 498) every three weeks for up to 17 cycles (approximately 12 months) or until participants experienced disease recurrence or unacceptable toxicities or withdrew consent. The analyzed data as of September 15, 2023, represented (https://doi.org/10.1056/nejmoa2312695) a median follow-up of 57.2 months. 

At 48 months, researchers observed (https://doi.org/10.1056/nejmoa2312695) a statistically significant (p = 0.005) improvement in overall survival of 91.2% in the pembrolizumab group compared to 86.0% in the placebo group. Overall, patients with clear-cell renal cell carcinoma who received pembrolizumab had a nearly 40% reduced risk of death during the first four years after surgery.

However, the researchers noted that pembrolizumab was associated with a higher incidence of serious adverse events of any cause (20.7% versus 11.5% with placebo) and grade 3 or 4 adverse events related to pembrolizumab (18.6% versus 1.2%)

Although surgery is often curative in early-stage renal cell carcinoma, about 50% of patients will experience disease recurrence, particularly those with higher disease stage or grade (https://doi.org/10.1016/S2589-7500(23)00095-X). In 2017, sunitinib was approved for adjuvant treatment of renal cell carcinoma with a high risk of recurrence, but it has a high rate of toxicity (https://doi.org/10.1056/nejme2402364) and limited evidence about extended survival. Accordingly, experts say (https://www.cancer.gov/news-events/cancer-currents-blog/2024/kidney-cancer-pembrolizumab-increases-survival) that it is “rarely prescribed” as adjuvant therapy. 

After the current findings, experts are recommending that pembrolizumab becomes standard of care following surgical resection of renal cell carcinoma, but evidence is sorely lacking. More studies about the biomarkers associated with the best outcomes (https://biomarkers.ons.org/biomarkers/) from pembrolizumab in renal cell carcinoma are needed.

Oncology nurses can learn more about pembrolizumab’s administration considerations (https://www.ons.org/podcasts/episode-174-administer-pembrolizumab-immunotherapy-confidence) on the Oncology Nursing Podcast.