Abstract PS2-06-20: Fr-popea: French real-world-data of peri-operative pembrolizumab KN522 regimen in extreme ages subgroups (<30 y.o and >70 y.o) with high-risk TNBC

Abstract Background: The current standard of care for early triple-negative breast cancer (eTNBC) patients is peri-operative pembrolizumab, as demonstrated by the improved pathological response and survival outcomes in the KEYNOTE-522 trial. However, the youngest and oldest patients are underrepresented in randomized clinical trials. Methods: The FR-POPEA study is a prospective, observational, subgroup cohort analysis of high-risk TNBC patients who were treated with perioperative pembrolizumab in the French KN522 Early Access Program (EAP) from April 2022 to November 2024. Eligible patients were adults with confirmed stage II-III TNBC (including ER 1-9% according to the French guidelines). Real-world data were collected through EAP forms completed by physicians. Clinical and safety data were collected until the end of the EAP or the end of the treatment. The oldest group was ≥70 years old (the control group was <70 years old), and the youngest group was <30 years old (the control group was ≥30 years old). Results: Over the 31-month duration of the EAP, a total of 7,687 patients were included from 427 different French healthcare centers. The oldest population represented 12.5% (n=962 patients) of the whole population (with a cutoff of ≥65y it represents 21,8% (n=1,678)). Notably there were 106 octogenarians and three nonagenarians. Compared to the control group, the oldest patients (≥65y) had higher rates of comorbidities such as cardiovascular disease (21.6% vs. 6.5%) and diabetes (12.6% vs. 4.7%), a greater proportion of stage III disease (43.6% vs. 38.4%), and a higher proportion of ECOG ≥1 (37.1% vs. 11.1%). Pembrolizumab was combined with a different chemotherapy regimen than KN522 trial in 5% of cases, compared to 1.2% in the control group. A total of 187 interruptions for pembrolizumab treatment were reported and 28.3% of them were due to an adverse reaction suspected to be immune-related (irAE) compared to 36.3% for the control group. Permanent discontinuations of pembrolizumab were documented in 178 patients (18.5%), with 41.6% due to an irAE (vs. 50.1% in the control group). A lower rate of breast-conserving surgery (60.6% vs. 64.2%) was observed. The pathological complete response (pCR) rate was lower among the oldest group (64.9% vs 72.4%). The youngest population represented 2% (n=153 patients) of the total cohort, increasing to 17.8% (n=1,370) when using an age cutoff under 40 years. The under 30y group exhibited a higher rate of family history of breast cancer (40.5% vs. 33.6%), a similar proportion of stage III disease (40.5% vs 39%) and a lower rate of ECOG≥1 (7.2% vs. 13.4%). Twenty-three interruptions for pembrolizumab were reported and 52.2% of them were due to an irAE (35.2% for the control group). Furthermore, pembrolizumab was permanently discontinued in 21 patients (13.7%) with 61.9% of them were due to an irAE (64.8% in the control group). Clinical outcomes indicated a higher rate of breast-conserving surgery (71.1% vs. 63.7%) and a slightly higher pCR rate (73.3% vs. 71.4%) compared to the control group. Conclusions: The FR-POPEA study is the largest real-world assessment of the KN522 regimen in both the oldest and youngest subgroups. These results offer valuable real-world confirmation of the feasibility, efficacy, and safety of peri-operative pembrolizumab combined with chemotherapy in early-stage TNBC. Although there is a lack of extensive data on BRCA mutation status and formal geriatric assessments, these outcomes are reassuring and complement evidence from randomized trials. Citation Format: M. Robert, A. de Nonneville, E. Volant, C. Liautard, C. Perkins, F. Penault Llorca, O. Tredan, J. S. Frenel. Fr-popea: French real-world-data of peri-operative pembrolizumab KN522 regimen in extreme ages subgroups (<30 y.o and >70 y.o) with high-risk TNBC [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 PS2-06-20.