Real-world outcomes of first-line pembrolizumab plus chemotherapy in metastatic triple-negative breast cancer with central nervous system metastases: A multicenter cohort from Poland, the Czech Republic, and Slovakia.

e13120 Background: Patients with metastatic triple-negative breast cancer (mTNBC) and central nervous system (CNS) metastases have an exceptionally poor prognosis and very short survival. In the KEYNOTE-355 trial, pembrolizumab in combination with chemotherapy demonstrated a survival benefit in patients with programmed death-ligand 1 (PD-L1) positive (combined positive score [CPS]≥10) mTNBC. Although patients with previously treated and stable CNS metastases were eligible (3% of the intention-to-treat population), efficacy outcomes for this subgroup have not been reported to date. Real-world evidence regarding the effectiveness of pembrolizumab-based chemotherapy in patients with mTNBC and CNS metastases remains limited. Methods: The CEBCC-101 real-world retrospective study evaluated the effectiveness of first-line pembrolizumab plus chemotherapy in patients with PD-L1–positive mTNBC across 20 oncology centers in Poland, the Czech Republic and Slovakia. Among 178 treated women, 14 (7.7%) had brain metastases at treatment initiation, all of which were stable following prior local therapy. Median overall survival (mOS) and progression-free survival (mPFS) were estimated using the Kaplan–Meier method with follow-up summarized descriptively. Results: The median age at initiation of systemic treatment was 52.5 years (IQR 44–67). Up to four metastatic lesions were identified in nine patients (64.3%), while the remaining patients (n = 5, 35.7%) presented with a higher intracranial tumor burden. The median diameter of the largest intracranial metastatic lesion was 20 mm (n = 11; IQR 13-28; range 5-36). All patients received radiotherapy as part of local treatment for brain metastases. Radiotherapy alone was administered in 10 patients (71.4%), while surgery followed by radiotherapy was performed in the remaining four cases (28.6%). Median follow-up was 10.2 months (Q1-Q3, 8.34-14.81; range 0.66–20.8). A total of 10 OS events and 13 PFS events were observed. The median OS was 10.4 months; OS rates at 3, 6, 9, 12, 15 and 18 months were 85.7%, 78.6%, 64.3%, 49%, 39.2% and 13.1%, respectively. The median PFS was 6.7 months; PFS rates at 3, 6, 9, and 12 months were 78.6%, 57.1%, 35.7%, and 7.1%, respectively. Conclusions: Patients with CNS metastases are more frequently encountered in real-world clinical practice than in clinical trial populations. In this multicenter real-world cohort of mTNBC with CNS metastases treated with first-line pembrolizumab plus chemotherapy, mOS and mPFS were markedly shorter than those reported for the overall population in the KEYNOTE-355 trial. These findings underscore the persistent unmet clinical need in mTNBC with CNS involvement and support further prospective evaluation and optimization of multimodal treatment strategies in this population.