Dr Zhang discusses recently approved adjuvant systemic therapy for patients with RCC who have a high risk of recurrence after nephrectomy.
Tian Zhang, MD: Thinking about the recently approved adjuvant systemic therapies in this space in the postoperative setting, where patients are otherwise radiographically without evidence of disease, we had adjuvant sunitinib, which wasn’t often given in practice because of the risk for toxicities. Those seem to outweigh the clinical benefit of increasing disease-free survival but not overall survival. That was only 1 of many TKI [tyrosine kinase inhibitor] studies in this space.
About a year ago, we saw high-level results of KEYNOTE-564, which was adjuvant pembrolizumab compared with placebo. These results were updated at this year’s GU ASCO [American Society of Clinical Oncology Genitourinary Cancers Symposium]. To give a quick summary in this population, the intent-to-treat population was anyone with a kidney cancer of T2 or higher or in node-positive disease. Of note, they included a population of patients with M1 disease—metastasectomy rendered with no evidence of disease after surgery.
For the intent-to-treat population, we saw an updated disease-free survival at 2 years of 78.3% compared with 67.3% for patients treated with pembrolizumab vs placebo. The hazard ratio I saw continued to be in the 0.6 range. It was 0.63 at this 30-month follow-up. There was an interesting benefit that we saw for the higher-risk populations: in pathologic, T4 disease, or any T stage with node-positive disease, we saw this high-risk population with benefit of the 2-year disease-free survival rates, 48.7% vs 35% for placebo. The highest disease-free survival benefit I saw was for that M1 treated population resected. In this population, there might be micrometastatic disease, or disease we don’t see. In that population, the 2-year disease-free survival rate was 38% for patients treated with placebo and 78% for patients treated with pembrolizumab for a year. That hazard ratio was quite different. It was 0.28 favoring pembrolizumab.
Finally, we saw a benefit also for sarcomatoid disease to go along with our prior conversation around histology. The benefit for patients treated with pembrolizumab was 71.8% at the 2-year mark vs 52% with a hazard ratio of 0.54. Of note, we didn’t see enough overall survival. There weren’t enough deaths on the study to warrant further overall survival differences between the 2 populations. More follow-up will be necessary to decide whether we’ll see an overall survival benefit and whether truly this early treatment with immunotherapy is more effective in the long term.
This transcript has been edited for clarity.