Abstract PD6-02: Impact of early magnetic resonance imaging assesment on prediction of pathologic complete response and long-term outcomes in triple-negative breast cancer treated with neoadjuvant pembrolizumab

Abstract BACKGROUND Previous studies suggest that radiological complete response (rCR) to neoadjuvant chemotherapy (NAC), assessed by magnetic resonance imaging (MRI), may predict pathologic complete response (pCR) in patients with operable triple-negative breast cancer (TNBC) treated with anthracycline (AC) and taxane (TX)-based regimens. At our institution, serial MRI assessments are performed before NAC, mid-treatment, and prior to surgery. This study aimed to assess the predictive value of MRI response in patients receiving a novel NAC regimen with pembrolizumab (pembro) an its correlation with pCR. If a strong correlation is confirmed, this could support future de-escalation strategies to reduce toxicity without compromising efficacy. We also compared this group to a historical cohort treated with standard NAC, to evaluate whether adding pembro improves pCR rates and long-term outcomes such as overall survival (OS) and event-free survival (EFS). METHODS We retrospectively analyzed 162 TNBC patients treated with NAC. Patients were divided into 2 cohorts:-Cohort 1 (n=140): historical cohort with patients treated from February 2000-March 2024 with sequential regimens: 116 received 4 cycles of AC every 3 weeks (wk) followed by TX weekly for 12 cycles, and 24 received the same adding carboplatin (in 21 patients with non-rCR, 2 with rCR and 1 without MRI after AC). Patients underwent MRI to assess tumour response before NAC, after 4 cycles of AC and after TX.-Cohort 2 (n=22): patients treated with new NAC based on KEYNOTE-522, from March 2023-March 2025. MRIs were performed before NAC, after 4 cycles of carboplatin + paclitaxel days 1,8,15 plus pembro day 1 every 3 wk, and after 4 cycles of AC + pembro every 3 wk. Treatment response was determined by histopathological examination. pCR was defined as absence of invasive tumor and nodal involvement. rCR was defined as no/minimal enhancement at the lesion site, comparable to normal tissue. Continuous variables were expressed as mean and standard deviation; categorical variables as absolute values and percentages. Chi-square or Fisher’s exact test was used to assess significance. Survival analysis was conducted using Kaplan-Meier curves and log-rank tests. A p-value 0.05 was considered statistically significant. RESULTS Median age at diagnosis was 52 years (range 28–77). Most patients had stage III disease (97.5%, AJCC 8th edition). The overall pCR rate (breast and axilla) was 44.4%, significantly higher in cohort 2 vs. cohort 1 (68.2% vs. 40.7%, p=0.016). Early rCR on MRI was achieved in 28.6% of patients overall, significantly more frequently in cohort 2 (66.6% vs. 22.7%, p0.001). Final rCR on MRI was achieved in 43.8% of patients overall (61.9% in cohort 2 vs. 40.8% in cohort 1, p=0.121). Among patients with early rCR (n=44), 84.1% achieved pCR (83.3% in cohort 1 vs. 85.7% in cohort 2). For those with rCR prior to surgery (n=64), the pCR rate was 82.8% (78.4% in cohort 1 vs. 100% in cohort 2). At 5 years, OS was 79% and EFS 81% for the overall cohort. Patients with pCR had significantly improved outcomes:-OS: 96.7% vs. 66.5% in non-pCR (p0.001)-EFS: 98.5% vs. 64.4% in non-pCR (p0.001) Patients with early rCR also had superior 5-year outcomes:-OS: 100% vs. 71.6% in non-responders (p0.001)-EFS: 100% vs. 70.5% in non-responders (p0.001) CONCLUSION In TNBC, adding pembro to NAC significantly increases early radiological and pathological complete response rates. Serial MRI during NAC are good predictors of pCR, correlating with improved long-term outcomes. The significant association between early rCR and pCR may serve as a non-invasive biomarker to guide therapeutic decisions and could be studied as a tool to de-escalate NAC especially in patients with comorbidities, older age or at high toxicity risk. Citation Format: A. Carrasco Navas, O. Cano i Cano, M. Seguí Palmer, E. Dalmau Portulas, P. Andreu Cobo, M. Costillas Frías, M. Medarde Ferrer, A. López Mestres, N. F. Papaleo, M. Busquets Godall, M. Fragío Gil, M. Sierra Boada, A. Ribas Bravo, O. Civit Figueras, C. Victoria Marin, J. Sandoval Alves, M. Monroe Rivera, I. Gallego Bernardo, S. Soriano Sánchez, J. Giner Joaquin, P. Ribera Fernández, L. Vila Martínez, R. Querol Niñerola, T. Bonfill Abella, E. Gallardo Díaz, L. Medina Ortega, B. Calvo Martínez, M. Rosich Peris, L. Fernández Morales. Impact of early magnetic resonance imaging assesment on prediction of pathologic complete response and long-term outcomes in triple-negative breast cancer treated with neoadjuvant pembrolizumab 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 PD6-02.