Abstract PS5-07-12: Opt-pembro: a phase III randomized trial of adjuvant pembrolizumab omission in patients with early-stage triple-negative breast cancer achieving pathologic complete response after neoadjuvant chemo-immunotherapy

Abstract Background: In early-stage triple-negative breast cancer (eTNBC), the addition of pembrolizumab to neoadjuvant chemotherapy followed by continued adjuvant immunotherapy significantly improved pathological complete response (pCR), event-free and overall survival (OS) in the KEYNOTE-522 trial. However, the continuation of pembrolizumab post-surgery in all patients, irrespective of response, raises concerns of overtreatment, toxicity, and cost. This is particularly evident in patients achieving pCR, who exhibit excellent long-term outcomes. The OPT-PEMBRO trial addresses whether adjuvant pembrolizumab can be safely omitted in this favourable-risk subgroup. Trial Design: OPT-PEMBRO is an international, multicenter, randomized, open-label, phase III non-inferiority trial sponsored by UNICANCER. It will enroll 2454 patients with stage T1cN1-2 or T2-4N0-2 TNBC who achieve pCR (ypT0 ypN0) following standard neoadjuvant chemotherapy plus pembrolizumab. Patients are randomized 1:1 within 12 weeks post-surgery to either continue standard adjuvant pembrolizumab (6 months) or observation alone. The primary endpoint is recurrence-free survival (RFS). Secondary endpoints include invasive breast cancer-free survival (iBCFS), distant relapse-free survival (DRFS), OS, safety, quality of life (EORTC QLQ-C30, BR42, EQ-5D-5L), immune-related adverse events (irAEs), patient-reported outcomes (PRO-CTCAE), and fertility impact. Translational objectives include assessment of baseline stromal TILs and their interaction with outcomes. Patient Population: Eligible patients are adults (≥18 years) with histologically confirmed stage T1cN1-2 or T2-4N0-2 TNBC (ER/PR ≤10%, HER2-negative), treated with ≥6 cycles of neoadjuvant chemotherapy plus pembrolizumab and achieving pCR. Additional criteria include ECOG 0-2, adequate organ function, no prior invasive breast cancer, and no evidence of residual disease or distant metastasis. Statistical Considerations: OPT-PEMBRO is powered to demonstrate non-inferiority of observation versus standard adjuvant pembrolizumab in terms of RFS, using a non-inferiority margin of 2.5% (HR 1.44). Interim analyses for futility are planned. A prospective meta-analysis with the U.S.-based OptimICE-pCR trial is also anticipated. Current Status: Trial enrolment is ongoing across centres in France and Belgium. A total of 2454 patients will be enrolled over 4 years, with an additional 4 years of follow-up. The final analysis is event-driven and expected after 285 RFS events. Long-term follow-up will extend to 14.5 years to assess OS, late toxicity, and survivorship. Conclusion: OPT-PEMBRO is an international randomized trial to test the non-inferiority of omitting adjuvant immunotherapy in patients with eTNBC presenting pCR following standard neoadjuvant chemotherapy plus pembrolizumab. By targeting a good-prognosis population, it aims to personalize immunotherapy duration, reduce toxicity, preserve quality of life, and lower healthcare costs without compromising outcomes. Citation Format: J. M. Ribeiro, F. Duhoux, E. Romano, B. Verret, F. Dalenc, E. Azambuja, S. Ladoire, A. Rorive, A. Mailliez, P. Bénédicte, C. Lefeuvre, D. Taylor, A. Gonçalves, K. Punie, M. Mouret-Reynier, C. Fontaine, C. Bailleux, E. Naert, P. Corbaux, F. Derouane, M. Leheurteur, E. Jacquet, M. Robert, A. Lemoine, T. Robinson, R. Salgado, M. Van Bockstaele, M. Lambertini, S. Tillaux, T. Sara, A. Partridge, L. Carrey, K. Pilger, J. Lemonier, S. Mardinian, S. Mijonnet, F. Clement-Bidard, T. Bachelot, V. Ines, S. Michiels, T. Olivier. Opt-pembro: a phase III randomized trial of adjuvant pembrolizumab omission in patients with early-stage triple-negative breast cancer achieving pathologic complete response after neoadjuvant chemo-immunotherapy [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 PS5-07-12.