Real-world effectiveness and safety of first-line pembrolizumab plus chemotherapy in patients aged ≥65 years with metastatic triple-negative breast cancer.

1124 Background: Patients aged ≥65 years constitute a substantial proportion of individuals with metastatic triple-negative breast cancer (mTNBC), but remain underrepresented in clinical trials due to comorbidities and concerns regarding treatment tolerability. While pembrolizumab combined with chemotherapy (P+C) has been established as a standard first-line treatment for mTNBC with a combined positive score ≥10, real-world evidence on its safety and effectiveness in older patients remains limited. Methods: This multicenter observational real-world study (RWS), CEBCC-101, retrospectively analyzed clinical data from 178 female patients with mTNBC treated with P+C in routine clinical practice. Patients were stratified according to age at treatment initiation (<65 vs. ≥65 years). Baseline characteristics, treatment modifications (including dose reductions and treatment delays), adverse events (AEs; graded according to CTCAE v5.0) and clinical outcomes were assessed. Clinical endpoints included progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) evaluated according to RECIST 1.1. Survival outcomes were estimated using the Kaplan–Meier method and compared between age groups using the log-rank test. Results: Among 178 patients, 57 (32.0%) were aged ≥65 years. Median age in the older cohort was 72.4 years (mean 72.3 ± 4.7). Patients ≥65 years had a significantly higher prevalence of relevant comorbidities compared with younger patients (71.9% vs. 39.7%; p<0.001) and more frequently presented with visceral metastases (78.9% vs. 61.2%; p=0.029), driven primarily by a higher incidence of lung metastases (59.7% vs. 42.2%; p=0.043). Rates of chemotherapy dose reductions at treatment initiation or during therapy, treatment delays due to AEs and treatment discontinuation due to toxicity were comparable between age groups. ORR did not differ significantly between patients ≥65 and <65 years (52.6% vs. 55.4%; p=0.767). Median PFS was 9.1 months (mo) in patients ≥65 years versus 8.3 mo in younger patients (p=0.594). Median OS was 22.1 mo and 19.5 mo, respectively (p=0.985). The incidence of grade ≥2 AEs, including pulmonary, neurological, dermatological events and fatigue was similar across age groups. Conclusions: In this RWS, patients aged ≥65 years with mTNBC treated with first-line P+C achieved clinical outcomes and safety profiles comparable to those of younger patients, despite a higher burden of comorbidities and more frequent visceral disease. These findings suggest that chronological age alone should not be a limiting factor for immunochemotherapy and underscore the importance of treatment decisions based on clinical fitness. Broader incorporation of geriatric assessment into routine oncology practice may further optimize patient selection and outcomes.