DFS benefits with adjuvant pembrolizumab in RCC persist with longer follow-up

Updated data from the KEYNOTE-564 trial showed continuous disease-free survival (DFS) advantage with pembrolizumab versus placebo as adjuvant therapy for renal cell carcinoma (RCC). With 33% of events needed, overall survival (OS) data are not yet mature, but the hazard ratio is currently declining.

Nephrectomy is the standard of care treatment for locoregional RCC. However, nearly half of the patients eventually experience disease recurrence after surgery which is associated with a shortened life expectancy. Effective perioperative therapy to reduce this risk remains an unmet need.

The phase 3, randomised KEYNOTE-564 trial (NCT03142334) evaluates the effect of pembrolizumab versus placebo as adjuvant therapy for patients with RCC. A total of 994 patients with histologically confirmed clear-cell RCC were enrolled in the study and randomised 1:1 to pembrolizumab or placebo. The primary endpoint was DFS in all randomised patients. OS was a key secondary endpoint, as well as safety and tolerability. The study met its primary endpoint at the first interim analysis [1]. Adjuvant pembrolizumab resulted in a statistically significant improvement in DFS versus placebo with 24 months of follow-up (HR 0.68; P=0.0010). Dr Toni Choueiri (Dana-Farber Cancer Institute, MA, USA) presented updated efficacy and safety results from KEYNOTE-564 with 6 months of additional follow-up [2].

At 30-month follow-up, DFS benefit with pembrolizumab was maintained (HR 0.63; P<0.0001) and was consistent across subgroups (M0 intermediate-high risk [n=855]: HR 0.68; M0 high-risk [n=76]: HR 0.60; and M1 NED [n=58]: HR 0.28). At 24 months, the estimated DFS rate was 78.3% with pembrolizumab versus 67.3% with placebo. A total of 66 OS events were observed at 30 months; 23 in the pembrolizumab arm and 43 in the placebo arm (HR 0.52; P=0.0048; the P-value did not cross the statistical hypothesis testing boundary for this endpoint). However, compared with results from the first interim analysis, the hazard ratio for OS is declining and significance is increasing (HR 0.54; P=0.0164 at 24 months follow-up vs HR 0.52; P=0.0048 at 30 months follow-up).

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

“Adjuvant pembrolizumab continues to demonstrate a DFS benefit versus placebo in patients with RCC, with no new safety signals,” concluded Dr Choueiri. “Additional follow-up is planned for OS analysis. This updated analysis supports adjuvant pembrolizumab as a new standard of care for patients with RCC withs risk features for recurrence.”

1. Choueiri T, et al. N Eng J Med 2021;385:683–694.
2. Choueiri T, et al. Pembrolizumab as post nephrectomy adjuvant therapy for patients with renal cell carcinoma: Results from 30-month follow-up of KEYNOTE-564. Abstract 290, ASCO GU 2022, 17–19 February.

 

Want to read more? Medicom has a featured interview with Dr Toni Choueiri (Dana-Farber Cancer Institute, MA, USA) about the trials following KEYNOTE-564: Large phase 3 trial tests novel combinations for metastatic RCC.

 

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Posted on 8 April 202215 February 2024