Purpose: Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, and Taiwan) participants enrolled in KEYNOTE-564. Materials and Methods: Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 17 cycles. The primary endpoint was DFS by investigator assessment. OS was a key secondary endpoint. Safety was a secondary endpoint. Results: The East Asian subgroup included 126 participants (pembrolizumab, n=58; placebo, n=68). Median follow-up was 62.1 months (range, 49.6 to 73.0 months). Hazard ratio for DFS with pembrolizumab versus placebo was 0.70 (95% confidence interval 0.41 to 1.20). Median DFS was not reached with pembrolizumab versus 58.8 months with placebo; estimated 48-month rate was 61.3% versus 51.2%. Hazard ratio for OS was 0.47 (95% confidence interval, 0.15 to 1.49). Median OS was not reached with pembrolizumab and placebo; estimated 48-month rate was 94.8% versus 91.2%. Treatment-related adverse events occurred in 70.7% of participants (29.3% grade 3 or 4) receiving pembrolizumab and 36.8% of participants (0.0% grade 3 or 4) receiving placebo. No pembrolizumab-related deaths occurred. Conclusion In the KEYNOTE-564 East Asian subgroup, adjuvant pembrolizumab provided DFS and OS benefits versus placebo and had a safety profile consistent with the global results. These results further support pembrolizumab as adjuvant treatment for East Asian patients with RCC at increased risk of recurrence after nephrectomy.

Cardiac patient simulators are commonly used in Japanese educational institutions; however, most institutions have not established concrete learning objectives or strategies for mastering physical examination of the circulatory system, including cardiac auscultation. In this study, we propose clear learning objectives and strategies for simulator practice for fifth-year medical students who have passed the objective structured clinical examination, and explored their educational effectiveness.
1)The subjects were fifth-year medical students (n=94) at the University of Miyazaki. Learning objectives were the mastery of the sequential physical examination and the ability to distinguish 6 cardiac findings, including normal status. The subjects were evaluated with a checklist before and after lectures and simulator practice.
2)The mean score (maximum score=14) significantly increased from before simulator practice (2.2±0.9) to after simulator practice (11.4±1.5; p<0.001). There was no difference in scores after practice among the cardiac diseases.
3)Before practice more than 50% of subjects could use a stethoscope on only right positions and could indicate only the maximum point of a cardiac murmur; in contrast, after practice more than 90% of the subjects could sequentially describe physical findings and accurately predict cardiac diseases.
4)In a questionnaire administered after practice, 83% of the subjects answered that all physicians should acquire proficiency in cardiac auscultation regardless of their specialty.
Simulator practice with clear learning objectives may help improve clinical examination skills when both time and human resources are limited. The reevaluation of the program's continuing educational effectiveness and the establishment of an iterative learning program will be needed.