Abstract PS4-07-25: Real World Analysis of Efficacy, Toxicity, and Treatment Patterns of Pembrolizumab-Containing Regimens for Older Adults with Early-Stage Triple Negative Breast Cancer

Abstract Background: Older adults are underrepresented in clinical trials of neoadjuvant chemotherapy and pembrolizumab for early-stage triple negative breast cancer (TNBC), limiting evidence to guide treatment in this population. Given the potential toxicity of multi-agent regimens, we examined treatment patterns, efficacy, and safety outcomes for patients ≥ 65 years who received neoadjuvant pembrolizumab containing treatments for early-stage TNBC. Methods: Through medical review at a National Cancer Institute-designated comprehensive cancer center, we abstracted records for those aged ≥ 65 years at the time of a stage I-III TNBC diagnosis during 08/2021-05/2024. Patients were included if they received a pembrolizumab-containing regimen as neoadjuvant therapy. The primary endpoint was relative dose intensity (RDI), defined as the average percent of planned neoadjuvant treatment received across agents. We also ascertained records for hospitalizations, early treatment discontinuation, immune related adverse events (IRAE), and pathological complete response (pCR) status at surgery. We examined associations between age (65-70) vs (70) and occurrence of these events. In addition, we examined if treatment-related factors including RDI, duration of neoadjuvant therapy, anthracycline receipt, and age were associated with pCR. We used Kruskal-Wallis rank sum test for continuous variables and chi-square test for categorical variables. Results: Overall, 85 women were included in analyses; median age was 70. At the time of diagnosis, n=13 (15%) had heart disease, n=4 (5%) lung disease, n=6 (7%) chronic kidney disease, and n=1 (1%) cognitive impairment. For treatment regimens, 42% (n=36) received KEYNOTE 522 (carboplatin + paclitaxel + doxorubicin + cyclophosphamide + pembrolizumab), 41% (n=35) received carboplatin + paclitaxel + pembrolizumab, 4 (5%) doxorubicin + cyclophosphamide, + taxane + pembrolizuamb, and 4 (5%) docetaxel + carboplatin + pembrolizumab. Across regimens, median RDI was 90% (range 20-100%), and 55% (n=47) receieved ≥85% RDI. During neoadjuvant therapy, 41% (n=35) of patients were hospitalized at least once, 6% of all patients (n=5) required ICU admission, and 41% (n=35) discontinued treatment early due to adverse events. Overall, 39% (n=33) experienced an IRAE, of which 49% (n=16) required steroids. There were 3 deaths attributed to neoadjuvant treatment, specifically pneumonitis, pneumonia/septic shock, and multi-organ failure. Patients age 70, when compared to ages 65-70, were more likely to experience IRAE (OR 2.8, p=0.024) and receive lower RDI (OR 0.3, p=0.013). Rates of hospitalization, early treatment discontinuation, and path CR did not differ by age. The overall pCR rate was 43%. Factors including RDI, treatment duration, anthracycline, hospitalizations, immune related adverse events, and age were not associated with pCR. Conclusions: In this real-world cohort, half of older adults with early-stage TNBC received a non-anthracycline containing chemotherapy regimen with pembrolizumab, most commonly carboplatin and paclitaxel. Early discontinuation of neoadjuvant therapy was frequent with nearly 45% not receiving ≥85% RDI. Rates of hospitalization, immune related adverse events, and death were high, while pCR rates were lower than reported in clincal trials. Safer, more effective treatments are needed for older adults with early-stage TNBC. Citation Format: C. Smith, A. Rami, T. Li, P. Patel, M. Ling, R. Freedman. Real World Analysis of Efficacy, Toxicity, and Treatment Patterns of Pembrolizumab-Containing Regimens for Older Adults with Early-Stage Triple Negative Breast Cancer 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 PS4-07-25.