Abstract PS5-03-18: Clinicopathological features and outcomes of triple-negative breast cancer relapsing after pembrolizumab-based neoadjuvant therapy

Abstract Background: Neoadjuvant pembrolizumab combined with paclitaxel and carboplatin followed by anthracycline and cyclophosphamide has become the standard of care for stage II-III early triple-negative breast cancer (TNBC). However, clinicopathological features and outcomes of metastatic relapse after neoadjuvant chemo-immunotherapy remain poorly documented. Methods: We conducted a retrospective analysis at Institut Curie Hospitals (France) including patients diagnosed with a metastatic relapse between Nomvember 2022 and May 2025, after having received pembrolizumab-based neoadjuvant regimen for early TNBC. Patients’ characteristics at early and metastatic settings were collected, as well as Distant Metastasis-Free Interval (DMFI, from primary diagnosis to metastatic relapse), Progression-Free Survival on 1st line therapy (PFS1, from the date of metastatic relapse) and Overall Survival (OS, from the date of metastatic relapse). Results: We identified N=32 patients out of 386 patients treated with neoadjuvant pembrolizumab who experienced metastatic relapse following a pembrolizumab-based neoadjuvant regimen. At primary diagnosis, all 32 tumors were TNBC, including N=3 tumors (9%) with low (1-9%) expression of hormone receptors and N=13 tumors (41%) with HER2low status. Strikingly, androgen receptor (AR) expression was apparently enriched, with N=8/22 (36%) primary tumors showing high (≥10%) AR expression. Most primary tumors were of grade 3 (N=25/32, 78%) and stage II (N=20, 63%). Only N=2/29 (7%) patients displayed a germline BRCA1/2 mutation. Following neoadjuvant chemo-immunotherapy, N=30 patients underwent surgery, of whom only N=5 patients (17%) had a pCR (RCB=0). Post-operative treatments were heterogeneous: N=11 patients (37%) received adjuvant pembrolizumab monotherapy, N=9 (30%) received capecitabine monotherapy, N=5 (17%) received a combination of both, N=3 (10%) were included in a clinical trial while N=2 (7%) relapsed before any adjuvant therapy. The median DMFI from initial diagnosis was 16 months, IQR[9-19], and most relapses (N=23, 72%) occurred during or within 6 months after the completion of adjuvant therapy. At relapse, median age was 43 years (IQR[37-50]). Visceral metastases were present in N=22 patients (69%), while brain and bone-only metastases were identified in N=6 (19%) and N=3 (9.4%) patients, respectively. A prior or concurrent local recurrence was observed in N=12 of patients (38%). Although N=13/24 tumors (54%) displayed a high PD-L1 CPS score, only 3 patients (9%) were rechallenged with pembrolizumab and chemotherapy as first line therapy. N=11 patients (34%) received standard chemotherapy, N=16 patients (50%) received sacitumab govitecan (SG) when olaparib and experimental therapy were each administered to N=1 patient (3%). After a median follow-up of 11.2 months, median PFS1 was 3.9 months [95%CI:2.4-5.5]. We found no prognostic impact of disease sites and no survival difference between standard chemotherapy (median PFS1: 3.7mo) and SG (4.1mo). N=15 deaths have been observed, with a median OS of 8.5 months [95%CI: 7.7-NA]. Updated results with longer follow-up will be presented. Conclusions: This real-world cohort of patients with TNBC relapsing after pembrolizumab-based neoadjuvant therapy shows an extremely poor prognosis upon metastatic recurrence, regardless of metastatic site and first line therapy. There remains a critical need to improve treatment strategies in this population. Citation Format: R. Kabirian, M. Gendreau, F. C. Bidard, F. Lerebours, A. Vincent Salomon, L. Djerroudi, P. H. Cottu, F. Coussy, J. Y. Pierga, L. Cabel, D. Loirat. Clinicopathological features and outcomes of triple-negative breast cancer relapsing after pembrolizumab-based neoadjuvant therapy [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 PS5-03-18.