Pembrolizumab Post-Nephrectomy Extends Distant Metastasis-Free Survival, PFS2 in RCC


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Toni K. Choueiri, MD, explains significant findings from the long-term efficacy analysis of the KEYNOTE-564 study and highlights the significance of these data for the field of RCC.

Toni K. Choueiri, MD

Toni K. Choueiri, MD

Adjuvant pembrolizumab (Keytruda) continues to show improved disease-free survival (DFS) in patients with renal cell carcinoma (RCC) following nephrectomy, also demonstrating prolonged distant metastasis-free survival (DMFS), time to first subsequent treatment, and time to second disease progression (PFS2), according to Toni K. Choueiri, MD.

The phase 3 KEYNOTE-564 trial (NCT03142334) investigated adjuvant pembrolizumab in patients with clear cell RCC who are at an increased risk of recurrence after nephrectomy. The study results demonstrated improved DFS with pembrolizumab compared with placebo. A post-hoc exploratory efficacy analysis of the trial, which was presented at the 2022 ASCO Annual Meeting, showed a 24-month DMFS rate of 80.1% with pembrolizumab vs 69.9% with placebo, as well as a 24-month time to first subsequent treatment rate of 86.5% and 79.3%, respectively. Additionally, pembrolizumab elicited a 30-month PFS2 rate of 92.5% vs 86.1% with placebo.1

“It’s important for the general oncology audience, nursing staff, and all health care providers who deal with oncology and kidney cancer to know that adjuvant pembrolizumab is now an option for patients to decrease the risk of disease recurrence,” Choueiri said in an interview with OncLive®.

In the interview, Choueiri explained significant findings from the long-term efficacy analysis of the KEYNOTE-564 study and highlighted the significance of these data for the field of RCC.

Choueiri is the medical director of International Strategic Initiatives, the director of the Lank Center for Genitourinary Oncology, the director of the Kidney Cancer Center, and a senior physician at Dana-Farber Cancer Institute. He is also the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School.

OncLive®: What served as the rationale for this post-hoc analysis of the KEYNOTE-564 trial and what key end points were explored?

Choueiri: The KEYNOTE-564 trial was featured for the first time in the plenary session of the 2021 ASCO Annual Meeting, which showed that adjuvant immunotherapy with the immune checkpoint inhibitor pembrolizumab improved DFS compared with placebo.

In this long-term analysis, presented 1 year later, we decided to explore some post-hoc analyses related to other important end points while waiting for the overall survival [OS] data on this study. We explored 3 important end points: DMFS, which is the time from metastatic disease to any cause of death; time to first subsequent drug treatment, which is the time to first subsequent therapy or any cause of death; and PFS2, which is the time from randomization to progression, next line of therapy, or any cause of death. We used the median time from randomization to data cutoff of 30.1 months for this analysis.

All 3 end points showed a statistically significant and clinically meaningful difference [favoring pembrolizumab], with hazard ratios ranging from 0.57 to 0.67. We concluded that these new end points are consistent with the primary analysis of DFS, and they affirm the clinical benefit of adjuvant pembrolizumab and further support the use of adjuvant pembrolizumab after nephrectomy as a standard of care in patients with localized RCC who are at an increased risk for recurrence.

What are the next steps for this research?

We continue to gather long-term efficacy data. The secondary end point of OS is extremely important. Soon, hopefully, we’ll embark on looking at specific biomarkers. We also continue to gather data about long-term safety in this study.

Have safety data remained consistent with previous findings from this study?

Yes. Between 24.1 and 30.1 months of follow up, [a difference of 6 months], we didn’t see any change in steroid use or adverse effects in patients receiving adjuvant pembrolizumab.

What does the future look like for pembrolizumab in RCC?

Pembrolizumab was approved [on November 17, 2021] by the FDA in the population of high-risk RCC. Now, we’re trying to [discern more details with this agent]. We launched the [phase 3] LITESPARK-022 trial [NCT05239728], where the control arm is not placebo anymore but adjuvant pembrolizumab. That trial is just opening to accrual. It’s an international study where the experimental arm is pembrolizumab plus the HIF-2α inhibitor belzutifan [Welireg], which has shown activity in metastatic disease.

What other exciting information was presented at ASCO?

There were many interesting topics in the plenary session and in my field of genitourinary cancer. Many studies in the adjuvant setting [were presented], as well as some analyses in the metastatic setting that were quite intriguing. It was a great meeting.


Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab for postnephrectomy renal cell carcinoma (RCC): expanded efficacy analyses from KEYNOTE-564. J Clin Oncol. 2022;40(suppl 16):4512. doi:10.1200/JCO.2022.40.16_suppl.4512

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