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
Year: 2026
Type: conference-abstract
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.
Source: Clinical Cancer Research
Authors: 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
Institutions: Institut Gustave Roussy, Institut Curie, Institut universitaire du cancer de Toulouse Oncopole, Université Libre de Bruxelles, Institut Jules Bordet, Centre Georges François Leclerc, Centre Hospitalier Universitaire de Liège, Centre Oscar Lambret, Hôpital de Jolimont, Centre Eugène Marquis, Institut Paoli-Calmettes, Ziekenhuis aan de Stroom, Centre Jean Perrin, Vrije Universiteit Brussel, Centre Antoine Lacassagne, Ghent University Hospital, Centre Hospitalier Universitaire de Saint-Étienne, Universitair Ziekenhuis Leuven, Centre Henri Becquerel, Centre National de la Recherche Scientifique, Franche-Comté Électronique Mécanique Thermique et Optique - Sciences et Technologies, Université de Franche-Comté, Institut de Cancérologie de l'Ouest, Peter MacCallum Cancer Centre, GZA Ziekenhuizen Campus Sint-Augustinus, GZA Ziekenhuizen, Peter MacCallum Cancer Foundation, Cliniques Universitaires Saint-Luc, University of Genoa, Inserm, Université Paris-Saclay, Dana-Farber Cancer Institute, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, UniCancer Group, Centre Léon Bérard
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7129722856
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