KEY TAKEAWAYS
- The KEYNOTE-564 phase III trial aimed to investigate and explore the impact of adjuvant pembrolizumab on DFS in subgroups defined by UISS risk groups and disease stages.
- Across UISS risk and stage subgroups, pembrolizumab consistently extended DFS compared to placebo, solidifying its role as standard care for high-risk RCC after nephrectomy.
The KEYNOTE-564 study investigated the use of pembrolizumab(pembro), an immunotherapy drug, as an adjuvant therapy after surgery for clear cell renal cell carcinoma (ccRCC) at high risk of recurrence. Pembro significantly prolonged disease-free survival (DFS) compared to placebo, with continued improvement observed after 30 months.
Tian Zhang and her research group spearheaded the study that aimed to report the results of a post hoc exploratory analysis, focusing on DFS within patient subgroups categorized by the UCLA Integrated Staging System (UISS) risk groups and disease stage.
Patients with histologically confirmed ccRCC (pT2, grade 4 or sarcomatoid, N0, M0; pT3 or pT4, any grade, N0, M0; any pT, any grade, N+, M0; or M1 with no evidence of disease [NED]) were randomly assigned in a 1:1 ratio to receive either intravenous pembro (200 mg) or a placebo every 3 weeks for up to 17 cycles (~1 year).
The study assessed DFS. The UISS risk groups were determined retrospectively from the TNM stage, Fuhrman nuclear grade, and Eastern Cooperative Oncology Group performance status (ECOG PS). These UISS groups included intermediate risk (pT2, grade 4, N0, M0; pT3, grade 1, N0, M0; or pT3, grades 2-4, N0, M0, ECOG PS of 0), high risk (pT3, grades 2-4, N0, M0, ECOG PS 1; pT4, any grade, N0, M0; or N1, M0), or M1 NED. Various other subgroups based on disease stage were also assessed.
Baseline characteristics were generally balanced across subgroups, and the median follow-up was 30.1 months (range, 20.8-47.5). Most of the 994 enrolled patients were in the UISS intermediate-risk category (n = 732 [73.6%]; pembrolizumab, n = 359; placebo, n = 373). Additionally, 195 patients (19.6%; pembrolizumab, n = 100; placebo, n = 95) were classified as UISS high risk, and 58 patients (5.8%; pembro, n = 29; placebo, n = 29) had M1 NED.
The results showed that DFS favored pembro over placebo in the UISS intermediate-risk group (HR, 0.65 [95% CI, 0.48-0.88]; 24-month rate: 81.5% vs. 72.4%), UISS high-risk group (HR, 0.77 [95% CI, 0.49-1.20]; 24-month rate: 65.0% vs. 55.9%), and M1 NED group (HR, 0.28 [95% CI, 0.12-0.66]; 24-month rate: 78.4% vs. 37.9%). Notably, DFS favored pembrolizumab across all patient subgroups based on disease stage.
The study found that adding adjuvant pembrolizumab effectively prolongs DFS across all RCC subgroups, solidifying its role as standard care for high-risk patients after nephrectomy. The research was sponsored by Merck Sharp & Dohme LLC.
Source: https://suo-abstracts.secure-platform.com/a/gallery/rounds/18/details/3288
Clinical Trial: https://clinicaltrials.gov/study/NCT03142334
Zhang T, Choueiri TK, Tomczak P, et al.’’ ADJUVANT PEMBROLIZUMAB FOR RENAL CELL CARCINOMA (KEYNOTE-564): EXPLORATORY ANALYSIS ACROSS UCLA INTEGRATED STAGING SYSTEM RISK GROUPS AND DISEASE STAGE.’’ Presented at SUO 2023, 24th Annual Meeting (Poster 15).
