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KEYNOTE-564 Update Adds Support For Adjuvant Pembrolizumab For High-Risk RCC

Longer follow-up of the phase III study shows a consistent disease-free survival benefit with the postsurgical use of pembrolizumab in patients with renal cell carcinoma and high-risk features
21 Feb 2022
Immunotherapy;  Renal Cell Cancer

Author: By Shreeya Nanda, Senior medwireNews Reporter 


medwireNews: Updated results from the phase III KEYNOTE-564 trial in patients with high-risk renal cell carcinoma (RCC) indicate that the disease-free survival (DFS) benefit offered by adjuvant pembrolizumab treatment is maintained with longer follow-up. 

The DFS gain “was observed across subgroups”, including by recurrence risk and the presence or absence of sarcomatoid features, said presenter Toni Choueiri, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, at the 2022 ASCO Genitourinary Cancers Symposium, held in San Francisco, California, USA. 

This updated analysis “further supports adjuvant pembrolizumab as a new standard of care for patients with RCC with risk features for recurrence”, he added. 

The investigators previously reported a prespecified interim analysis of the double-blind, randomised trial, which showed a significant 32% reduction in the risk of recurrence or death with the use of adjuvant pembrolizumab versus placebo at a median follow-up of 24.1 months. 

Now, Toni Choueiri has presented data with an additional 6.0 months of follow-up – that is, at a median of 30.1 months – noting that treatment with pembrolizumab 200 mg every 3 weeks for about a year was associated with a significant 37% lower risk of recurrence or death relative to placebo. The 24-month DFS rates were 78.3% and 67.3%, respectively. 

The study enrolled 994 patients with intermediate-high-risk disease (pT2, grade 4 or sarcomatoid, N0, M0 or pT3, any-grade, N0, M0), high-risk disease (pT4, any grade, N0, M0 or any pT, any grade, N+, M0) or M1 no evidence of disease (NED) after surgery. 

Most (86.5%) of the participants fell into the intermediate-high-risk category, and in this subgroup, adjuvant pembrolizumab treatment led to a significant 32% decrease in the risk of recurrence or death compared with placebo; the respective 24-month DFS rates were 81.1% and 72.0%. 

The risk reduction afforded by adjuvant pembrolizumab was even greater in the high-risk (7.6% of patients) and M1 NED (5.8% of patients) subgroups, at a significant 40% and 72%, respectively. At the 24-month mark, the DFS rates with pembrolizumab versus placebo were 48.7% versus 35.4% in the high-risk subgroup and 78.4% versus 37.9% in the M1 NED subgroup. 

Similarly, patients with RCC lacking sarcomatoid features had a risk reduction of 37% with pembrolizumab relative to placebo, while those with sarcomatoid features had a 46% risk reduction. The DFS rates at 24 months were 79.5% versus 69.4% and 71.8% versus 52.0%, respectively. 

The presenter told the audience that only 33% of the deaths required for the final overall survival analysis had occurred at data cutoff, and although the hazard ratio for death of 0.52 favours the PD-1 inhibitor, the analysis did not meet the prespecified criteria for statistical significance and longer follow-up is needed. 

He added that there was “no notable increase” in the incidence of any-grade or grade 3–5 adverse events (AEs) with additional follow-up, nor was there an increase in the use of high-dose corticosteroids for immune-mediated AEs. And “[l]ate onset of treatment-related AEs was rare”, said Toni Choueiri. 

For instance, the rate of all-cause grade 3–5 AEs in the pembrolizumab group was 32.2% in the updated analysis and a nearly identical 32.4% in the primary analysis. The corresponding rates of grade 3 or 4 treatment-related AEs were 18.6% and 18.9%, while 7.6% and 7.4% of pembrolizumab-treated patients needed high-dose corticosteroids in the two analyses. 

The discussant – Daniel Geynisman, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, USA – said that after seeing these results, he “will feel more comfortable recommending adjuvant pembrolizumab”, especially for “super high-risk patients”, such as those with sarcomatoid features or those in the M1 NED subgroup. 

But Daniel Geynisman stressed that “a personalised discussion is absolutely necessary.” 


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

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

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