Abstract PS2-02-09: Fr-pop: Real-world data from 7,687 high-risk TNBC patients treated with perioperative pembrolizumab in France

Abstract Background: Since the KEYNOTE-522 trial demonstrated improved pathological response and survival outcomes, pembrolizumab in combination with neoadjuvant chemotherapy, followed by adjuvant administration, is the current standard of care for stage II-III triple-negative breast cancer (eTNBC). Objective: This prospective national observational cohort analysis aims to describe real-world data from high-risk eTNBC patients treated with this schema through the French KN522 Early Access Program (EAP) from April 13, 2022, to November 20, 2024. Methods: Eligible patients were adults with confirmed stage II-III TNBC, including ER 1-9% according to French guidelines. Data were collected via physician-completed EAP forms and patient-reported EORTC QLQ-C30 questionnaires. Clinical and safety data were recorded until the EAP concluded or the end of the treatment. Results: A total of 7,687 patients were enrolled during the 31-month EAP across 427 healthcare centers and by 1,259 physicians. Participating centers included comprehensive cancer centers (34%), private clinics (34.1%), and public hospitals (31.8%). Median age of patients was 52 years (range 19-92 years) including 21.8% >65 years old and mean BMI was 26.3 kg/m2 (IQR 22.2 - 29.4). 3002 (39,1%) patients had stage III disease, and 87.5% had an ECOG-PS of 0. Pembrolizumab was administered at the planned dose of 200 mg every three weeks for nearly all patients and 96.1% planned the chemotherapy regimen used in KN522 (carboplatin/paclitaxel -anthracycline/cyclophosphamide). A total of 1105 patients (14.4%) have temporary interrupted pembrolizumab treatment, predominantly during the neoadjuvant phase (74.3%), with 38.1% related to immune-mediated adverse events. The median duration of this interruption was 13 days. 1240 patients (16%) have permanently discontinued pembrolizumab with the main cause being suspected immune-related toxicity (49.1%). The second reported reason for permanent discontinuation was physician decision related to the pathological response (19.3%), whether it was complete (6.3%) or not (13%). The breast-conserving surgery rate was 63,8%, with a median interval of 28 days between the completion of neoadjuvant therapy and surgery. The overall pathological complete response (pCR) rate was 71.6%. For patients who experienced treatment interruption due to immune toxicity (n=737), the pCR rate was 71.2% and was 73.3% for patients younger than 30 years old (n=45). Additional systemic treatments were received by 8.8% of patients in the adjuvant phase (with a higher incidence for patients with residual disease). In most cases, it was chemotherapy, but PARPi and endocrine therapies were also reported. Quality of life data, assessed via the QLQ-C30, showed stable global health scores (mean score of 85.3 at neoadjuvant Cycle one (n=423) vs. 81.3 at adjuvant Cycle nine (n=40)). Pharmacovigilance reported a total of 417 serious treatment-related cases, including eight deaths. Conclusions: Thanks to the substantial participation of physicians and centers across France, FR-POP represents one of the largest real-world cohorts collecting relevant efficacy and safety data on KN522 regimen in clinical practice. With an observed pCR rate exceeding 70% despite the high proportion of stage III tumors, and in a non-selected and older population, these findings clearly point out the efficacy of this treatment strategy and the external validity of KN522 results. However, underreporting of adverse events and the absence of follow up after the end of treatment remain potential limitations of EAP-derived safety data and tolerance of this regimen should continue to be closely monitored. Citation Format: A. de Nonneville, D. Loirat, J. Ribeiro, S. Becourt, M. Benderra, N. Benard, M. Campone, F. Dalenc, O. Derbel, I. Desmoulins, A. Deleuze, G. Emile, A. Goncalves, J. Grenier, W. Jacot, C. Liautard, L. Mansi, M. A. Mouret Reynier, C. Perkins, B. Pistilli, J. P. Spano, A. Vasseur, F. Penault Llorca, O. Tredan. Fr-pop: Real-world data from 7,687 high-risk TNBC patients treated with perioperative pembrolizumab in France [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 PS2-02-09.