Rana R. McKay, MD

Invited discussant of the KEYNOTE-564 trial, Rana R. McKay, MD, Associate Professor of Medicine and Urology at the University of California San Diego, offered these comments about the trial results.

“This is a positive study, showing a 32% reduction in the risk of recurrence or death with adjuvant pembrolizumab vs placebo,” Dr. McKay told listeners. “The survival curves separate early at 12 weeks and continue to separate over time. Pembrolizumab favored all subgroups, independent of PD-L1 expression, and the benefit was maintained in M1 and M0 disease. A subanalysis of the study is needed to assess benefits in subgroups.”

“There was an early signal of an overall survival benefit, even though just 26% of the events needed for a final survival analysis had occurred. The safety of pembrolizumab is comparable to what is observed in metastatic disease. The quality-of-life data will be important to assess the risk vs benefit of this approach. We need to take into account disease-free survival, overall survival balanced with the risk of overtreatment, toxicity, quality of life, and cost,” Dr. McKay continued.

“I would argue that these data are practice-changing and represent a paradigm shift. This is the first positive phase III study of adjuvant immunotherapy in renal cell carcinoma. The prolongation of disease-free survival represents a clinical benefit. Given the magnitude of benefit and limited toxicity, adjuvant pembrolizumab represents a quantum leap forward for our patients and provides a new option for patients with clear cell renal cell carcinoma,” stated Dr. McKay.

Progress of Adjuvant Therapy

There are several ongoing studies looking at immunotherapy and combinations in the adjuvant setting. Dr. McKay pointed out that in the past, adjuvant cytokine therapy failed to improve survival after nephrectomy. Adjuvant studies of tyrosine kinase inhibitors were mainly negative. Given the success of immunotherapy in the metastatic setting, it was logical to explore it in the adjuvant setting.

Dr. McKay commented to The ASCO Post that the field is moving quickly. At the time her ASCO presentation was recorded, the sole indication for adjuvant checkpoint inhibitor therapy was in the treatment of melanoma. Since then, the U.S. Food and Drug Administration approved nivolumab for resected esophageal and gastroesophageal junction cancers, and promising data have also emerged from CheckMate 274 in patients with urothelial carcinoma post-resection and from KEYNOTE-522 in patients with breast cancer. 

DISCLOSURE: Dr. McKay has served as a consultant or advisor to Astellas, Medivation, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera Biosciences, Caris, Dendreon, Exelixis, Janssen, Merck, Novartis, Pfizer, Sanofi, Tempus, and Vividion Therapeutics; and has received institutional research funding from Bayer, Pfizer, and Tempus.