Dr. Choueiri explains significance of updated adjuvant pembrolizumab data in RCC

After FDA approval of pembrolizumab (Keytruda) last year, many researchers and clinicians are interested to find out the long-term efficacy of this treatment.

Investigators of a recent study presented at the 2022 ASCO Genitourinary Cancers Symposium reported favorable outcomes of pembrolizumab in patients with renal cell carcinoma (RCC) at 30-month follow up.1 In this interview, lead author Toni K. Choueiri, MD, discusses the benefit of these findings for high-risk patients and the need for continued follow-up of pembrolizumab. Choueiri is a professor of medicine at Harvard Medical School, and an attending physician, director of the Genitourinary Oncology Disease Center, and director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts.

Please discuss the background for this study.

Keynote-564 [NCT03142334] is an international randomized phase 3 trial of patient with confirmed clear cell renal cell carcinoma. These patients were randomized to receive pembrolizumab vs placebo in a one-to-one fashion for a year. Patients needed to have intermediate high-risk [renal cell cancer]. We defined it as T2 high grade or T3. High risk [was defined as] intermediate, high [or] high [risk], which is T4 or node positive, or patients with metastatic disease that is completely resected. As long as it's not in the brain or in the bone within a year, they could also be in this study. As I said, [we investigated] 1 year of pembrolizumab vs 1 year of placebo. The primary end point was investigator-assessed disease free survival, with safety and overall survival being secondary end points.

What were some of the notable findings of this study? Were any of them surprising to you or your co-authors?

We presented the first results during the plenary session at the 2021 ASCO [meeting], showing a disease-free survival advantage [in favor of] pembrolizumab over placebo. This was the first immunotherapy to show activity in renal cell cancer of high risk. This led to the approval of single-agent pembrolizumab in [this] population. Now, what we did in the GU 2022 tool and the ASCO GU is provide 6 more months [of updates], where we found that the hazard ratio for disease free survival was actually maintained from 0.68 to 0.63. The difference in disease-free survival went from 9% to 11%, favoring pembrolizumab.

How will these findings affect the way that you manage renal cell carcinoma in the future?

These findings, overall, continue. It's important with more follow-up [and] different data cut offs to have consistent results. These are consistent results that continue to demonstrate a disease-free survival benefit of pembrolizumab adjuvant vs placebo in the participant with RC at intermediate, high, or high-risk or M1 NED after surgery. We also found that there [are] no new safety signals.

What is the take-home message for the practicing urologist?

I think that this updated analysis of Keynote-564 further supports adjuvant pembrolizumab as a new standard of care for patients with RCC, with high risk of recurrence.

Is there anything else you feel our audience should know about this topic?

I think the study continues to evolve, to collect more data about other end points, such as overall survival. We had a preliminary look, in addition, for overall survival that showed [that] the hazard ratio and the confidence interval continued to get tighter, although it was not statistically significant. So, we're going to continue looking at overall survival. [It is] important also [that] there will be biomarkers studied [from] Keynote 564 [in the future].

Reference

1. Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab as post nephrectomy adjuvant therapy for patients with renal cell carcinoma: Results from 30-month follow-up of KEYNOTE-564. Paper presented at: 2022 ASCO Genitourinary Cancers Symposium; February 17-19, 2022; San Francisco, California. Abstract #290