1. The overall survival at 48 months was 91.2% in the pembrolizumab group vs 86.0% in the placebo group, with an HR 0.62 (significant).

2. Adverse events grade 3 or higher occurred in 18.6% of the pembrolizumab group vs 1.2% in the placebo group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Adjuvant therapy for localized renal-cell carcinoma has historically seen limited success. However recently, Pembrolizumab, an anti-PD-1 antibody, was shown to have some benefit in the adjuvant setting. This paper is a third prespecified interim analysis of the previous trial. The primary endpoint was disease-free survival (DFS), and secondary endpoints included overall survival (OS), safety, and quality of life (QoL). The median follow-up time was 57.2 months. DFS at 48 months was 64.9% in the pembrolizumab group vs 56.6% in the placebo group, with an HR 0.72 (significant). OS at 48 months was 91.2% in the pembrolizumab group vs 86.0% in the placebo group, with an HR 0.62 (significant). 79.5% in the pembrolizumab group and 81.4% in the placebo group received some form of subsequent therapy. With regards to safety, adverse events grade 3 or higher occurred in 18.6% of the pembrolizumab group vs. 1.2% in the placebo group. QoL in both groups remained generally stable. The strengths of the study included the follow-up period, whereas the limitations included the sample size. Overall, this study found that among patients with clear-cell renal-cell carcinoma, adjuvant therapy with pembrolizumab had improved outcomes.

Click to read the study in NEJM

Relevant Reading: Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma

In-Depth [randomized controlled trial]: This phase 3, double-blind, placebo-controlled trial enrolled patients who are status post-surgery for clear-cell renal-cell carcinoma of any stage (including M1 with no evidence of disease post-surgery) and randomized them (1:1) into adjuvant pembrolizumab (n=496) or matched placebo (n=498). Median follow-up time was 57.2 months (47.9-74.5). DFS at 48 months was 64.9% (95%CI, 60.3-69.1) in the pembrolizumab group vs 56.6% (95%CI, 52.0-60.9) in the placebo group, with an HR 0.72 (95%CI, 0.59-0.87). OS at 48 months was 91.2% (95%CI, 88.3-93.4) in the pembrolizumab group vs 86.0% (95%CI, 82.6-88.8) in the placebo group, with an HR 0.62 (95%CI, 0.44-0.87, p=0.005). 79.5% in the pembrolizumab group and 81.4% in the placebo group received some form of subsequent therapy. With regards to safety, adverse events grade 3 or higher occurred in 18.6% of the pembrolizumab group vs. 1.2% in the placebo group. QoL in both groups remained generally stable. Overall, this study found that among patients with clear-cell renal-cell carcinoma, adjuvant therapy with pembrolizumab had improved outcomes.

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