Updates Results of Adjuvant Pembrolizumab in RCC Shows Sustained DFS Benefit


Updated findings from the phase 3 KEYNOTE-564 trial may further support adjuvant pembrolizumab as a new standard of care for patients with renal cell carcinoma with high risk of recurrence.

Toni Choueri, MD

Toni Choueri, MD

The use of adjuvant pembrolizumab as treatment of patients with renal cell carcinoma (RCC) who are at high risk of recurrence continued to demonstrate improved disease-free survival (DFS) compared with placebo, according to an updated analysis of the phase 3 KEYNOTE-564 trial (NCT03142334).1

The findings were reported by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School in Boston, Massachusetts during the 2022 Genitourinary Cancers Symposium in San Francisco, California.

Previously reported data from KEYNOTE-564 found that treatment with adjuvant pembrolizumab yielded a statistically significant and clinically meaningful DFS benefit versus placebo in the intent-to-treat population (HR, 0.68, 95% CI: 0.53-0.87, P = .001).2 The 2022 GU Symposium presentation consisted of an updated efficacy and safety analysis with 30.1months of follow-up.

KEYNOTE-564 evaluated patients with RCC defined as intermediate-high risk (pT2, grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0), high-risk (pT4, any grade, N0, M0; any pT, any grade, N+, M0) and M1 no evidence of disease (NED) following surgery. Patients randomized 1:1 to receive either pembrolizumab, 200 mg every 3 weeks (n = 496) or placebo every 3 weeks (n = 498).

Median patient age was 60 years in both the treatment and placebo groups. A total of 347 patients in the pembrolizumab group were male (70.0%) versus 359 patients (72.1%) in the placebo group. Regarding risk category, 427 patients were intermediate-high risk (86.1%), 40 patients (8.1%) were high risk, and 29 patients (5.8%) were M1 NED in the treatment group versus 433 (86.9%), 36 (7.2%), and 29 (5.8%) in the placebo group, respectively. In the treatment group, there 52 patients (10.5%) in whom sarcomatoid features were present versus 414 patients (83.5%) in whom sarcomatoid features were absent, compared with 59 (11.8%) and 415 (83.3%) in the placebo group.

For the primary end point of DFS, benefit was maintained in patients receiving pembrolizumab (HR, 0.63, 95% CI: 0.50-0.80, nominal P < .0001) and was as follows across the 3 subgroups

  • Intermediate-high risk: HR, 0.68 (95% CI: 0.52-0.89)
  • High risk: HR, 0.60 (95% CI: 0.33-1.10)
  • M1 NED: HR, 0.28 (95% CI: 0.12-0.66)

“The estimated DFS rate at 24 months was 78.3% with pembrolizumab versus 67.3% with placebo…The estimated [overall survival] rate at 24 months was 96.2% with pembrolizumab versus 93.8% with placebo,” wrote the authors.

In the primary analysis of KEYNOTE-564, presented at 24.1 months’ follow-up, 470 patients (96.3%) in the pembrolizumab group experienced an all-cause adverse event (AE) versus 452 (91.1%) in the placebo arm; in the updated findings presented at the 2022 ASCO GU Symposium, the number of patients in the pembrolizumab arm experiencing an all-cause AE was unchanged compared with 453 patients (91.3%) in the placebo arm. Grade 3-4 AEs were also very similar for the pembrolizumab arm at 24.1 months and 30.1 months with 42 patients (8.6%) and 43 patients (8.8%) respectively, compared with 3 patients (0.6%) in the placebo arm at 24.1 and 30.1 months.

“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,” Choueiri told Targeted Oncology, in an interviews.


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. J Clin Oncol. 2022;40(suppl 6):abstr 290. doi:10.1200/JCO.2022.40.6_suppl.290

2. Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385(8):683-694. doi:10.1056/NEJMoa2106391

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