Pembrolizumab for Early‐Stage Triple‐Negative Breast Cancer: KEYNOTE ‐522 Japan Subgroup Analysis

The phase 3 KEYNOTE-522 study in high-risk early-stage triple-negative breast cancer (TNBC) showed significantly improved efficacy outcomes with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab versus neoadjuvant chemotherapy alone. We present findings from the KEYNOTE-522 Japan subgroup. Eligible participants (aged ≥ 18 years) with untreated locally advanced TNBC (stage T1c N1-2 or T2-4 N0-2) were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo plus chemotherapy every 3 weeks for 8 cycles followed by surgery and adjuvant pembrolizumab or placebo for ≤ 9 cycles. Primary endpoints were pathologic complete response (pCR; ypT0/Tis ypN0) at the time of surgery and event-free survival (EFS). Of 76 participants enrolled in Japan, 45 were randomized to the pembrolizumab arm and 31 to the placebo arm. Median time from randomization to data cutoff (March 22, 2024) was 76.3 months. Twenty-four participants (53%) in the pembrolizumab arm and 15 (48%) in the placebo arm achieved pCR (between-treatment arm difference, 4.9%; 95% CI, -17.6% to 27.1%); findings were similar regardless of PD-L1 expression. Rates of EFS at 60 months were 84% and 73%, respectively (HR, 0.54; 95% CI, 0.20-1.50). Grade 3 or 4 treatment-related AEs occurred in 37 of 45 participants (82%) treated with pembrolizumab and 23 of 30 participants (77%) treated with placebo; there were no grade 5 AEs. In conclusion, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab showed improved efficacy outcomes and manageable safety versus neoadjuvant chemotherapy alone in Japanese participants, supporting the use of this regimen in Japanese patients with high-risk early-stage TNBC. Trial Registration: The study (ClinicalTrials.gov, NCT03036488) was conducted in compliance with local and/or national regulations and International Council for Harmonization Good Clinical Practice guidelines and in accordance with the ethical principles originating from the Declaration of Helsinki.