Abstract PS4-07-27: Pembrolizumab + chemotherapy vs placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs placebo as adjuvant treatment for early-stage TNBC: a post hoc analysis of participants included and separately of those not included in the first interim analysis for pCR in the KEYNOTE-522 study

Abstract Background: In the phase 3 KEYNOTE-522 (NCT03036488) study in participants (pts) with early-stage TNBC, addition of pembrolizumab (pembro) to chemotherapy (chemo) led to statistically significant and clinically meaningful improvements in pCR, EFS, and OS at interim analysis 1 (IA1), IA4, and IA7, respectively. At the prespecified IA1 (per approved statistical analysis plan), pembro + chemo showed statistically significant pCR when compared to chemo alone in the first 602 pts who underwent randomization. However, the difference in pCR rates between treatment arms decreased at IA4, which was evaluated in the overall population. A post hoc subgroup analysis was conducted to separately evaluate outcomes (EFS, OS) in the group of pts who were included in the IA1 pCR analysis and pCR, EFS, and OS in the group of remaining pts who were not. Methods: Eligible pts had previously untreated, high-risk, early-stage TNBC. Pts were randomized 2:1 to receive neoadjuvant pembro + chemo followed by adjuvant pembro (pembro arm) or neoadjuvant placebo + chemo followed by adjuvant placebo (placebo arm). Dual primary endpoints were pCR (ypT0/Tis ypN0) per local pathologist and EFS per investigator; OS was a key secondary endpoint. Data cutoff dates were March 23, 2021 (IA4) for pCR and March 22, 2024 (IA7) for EFS and OS. Results: The first 602 pts who underwent randomization were included in the IA1 pCR analysis and the remaining 572 pts were not included as per statistical analysis plan. Baseline pt characteristics were generally balanced between the treatment arms in both groups (included in IA1: 99.8% female; median age, 49 years; 64% White; 23% Asian; 75% with stage II disease; 74% with tumor size T1/T2; 52% with positive nodal status; 50% with PD-L1 CPS ≥10; not included in IA1: 100% female; median age, 48 years; 63% White; 18% Asian; 75% with stage II disease; 75% with tumor size T1/T2; 51% with positive nodal status; 47% with PD-L1 CPS ≥10). Efficacy outcomes are shown in the Table. HRs for EFS and OS were similar and favored the pembro arm versus the placebo arm in both groups. Conclusions: In this post hoc analysis of the KEYNOTE-522 study, the pCR rate in the group of pts who were not included in IA1 for pCR was found to be similar between the treatment arms. EFS and OS outcomes favored the pembro arm versus the placebo arm with similar HRs in both groups and were consistent with those in the overall study population. These data support the use of pembro in combination with neoadjuvant chemo, then continued as adjuvant monotherapy after surgery for high-risk, early-stage TNBC. Citation Format: P. Schmid, J. Cortes, L. Pusztai, H. McArthur, S. Kümmel, C. Denkert, Y. H. Park, R. Hui, N. Harbeck, M. Takahashi, T. Foukakis, P. A. Fasching, F. Cardoso, M. Untch, Y. Ding, F. Beca, J. A. Mejia, R. Dent, J. O’Shaughnessy. Pembrolizumab + chemotherapy vs placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs placebo as adjuvant treatment for early-stage TNBC: a post hoc analysis of participants included and separately of those not included in the first interim analysis for pCR in the KEYNOTE-522 study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-27.