ASCO GU 2022: Pembrolizumab As Post Nephrectomy Adjuvant Therapy for Patients With Renal Cell Carcinoma: Results From 30-Month Follow-Up of KEYNOTE-564

( In an oral abstract on the third day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 focused on renal cell cancer, Dr. Choueiri presented 30-month follow-up from the KEYNOTE-564 trial of post-nephrectomy adjuvant pembrolizumab in patients with renal cell carcinoma (RCC).

While nephrectomy is the standard of care for patients with locoregional RCC, the risk of recurrence for patients with high-risk disease is high. Thus, adjuvant therapy has been pursued for many years. In general, adjuvant tyrosine kinase inhibitors did not offer significant clinical benefits. However, the double-blind, multicenter, randomized KEYNOTE-564 study (NCT03142334) demonstrated that adjuvant pembrolizumab in patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence after nephrectomy or nephrectomy and resection of metastatic lesions resulted in a statistically significant improvement in disease-free survival (DFS) vs placebo with 24 months of follow-up (HR 0.68, 95% CI 0.53−0.87; p = 0.0010).

While previously presented and published, in brief, KEYNOTE-564 enrolled patients with histologically confirmed, clear cell RCC (pT2, grade 4 or sarcomatoid, N0 M0; pT3 or pT4, any grade, N0 M0; any pT, any grade, N+ M0; or M1 NED [no evidence of disease after primary tumor and soft tissue metastases completely resected ≤1 year from nephrectomy]) who had undergone surgery ≤12 weeks prior to randomization. Patients were then randomized to receive adjuvant pembrolizumab or placebo.

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The primary endpoint was DFS by investigator assessment in all randomized patients (ITT population) while overall survival in the ITT population, and safety/tolerability in all treated patients, were key secondary endpoints. While the previous publication presented results with 24 months of follow-up, this updated analysis provides an additional 60 months of follow-up to 30 months.

The KEYNOTE-564 trial randomized 994 patients in a 1:1 fashion to pembrolizumab (N = 496) or placebo (N = 498). As of data cut-off of June 14, 2021, the median (range) follow-up duration was 30.1 (20.8−47.5) months.

In this updated analysis, DFS benefit with pembrolizumab was maintained (HR 0.63, 95% CI 0.50−0.80; nominal P < 0.0001). The estimated DFS rate at 24 months was 78.3% with pembrolizumab vs 67.3% with placebo. Compared to the primary analysis at 24 months of follow-up, this updated analysis had very comparable findings, with a somewhat larger magnitude of effect (HR 0.63 vs 0.68).

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Further, this benefit of adjuvant pembrolizumab was consistent across subgroups, including those defined by age, sex, ECOG performance status, region of residence, tumor grade, and PD-L1 status.

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When stratified by recurrence risk subgroups, the benefit of adjuvant pembrolizumab was seen in patients with M0 disease with intermediate-high risk of recurrence (HR 0.68, 95% CI 0.52−0.89), M0 high risk of recurrence (HR 0.60, 95% CI 0.33−1.10), or M1 NED (HR 0.28, 95% CI 0.12−0.66).


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The benefit of adjuvant therapy was even larger among those with sarcomatoid features (HR 0.54, 95% CI 0.29-1.00) than those without (HR 0.63, 95% CI 0.48-0.83).

A total of 66 OS events were observed, 23 in the pembrolizumab arm and 43 in the placebo arm (HR 0.52, 95% CI 0.31−0.86; P = 0.0048), though the p-value did not cross

the statistical hypothesis testing boundary (of p=0.000095) and additional follow-up is planned for this key secondary endpoint. The estimated OS rate at 24 months was 96.2% with pembrolizumab vs 93.8% with placebo. Compared to the primary analysis, the magnitude of benefit increase somewhat with increasing follow-up.

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With additional follow-up, there was no increase in any-grade or grade 3-4 adverse events or steroid use for immune-mediated adverse events observed. No deaths related to pembrolizumab occurred.

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In conclusion, Dr. Choueiri highlighted that adjuvant pembrolizumab continued to demonstrate a DFS benefit following nephrectomy for intermediate-high or high risk of recurrence after surgery.

Presented by: Toni K. Choueiri, MD, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School