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.
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.
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.
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.
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.
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].
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