Abstract PS4-10-06: Analysis of Adverse Events and Outcomes of Adjuvant Therapies in TNBC as Monotherapy and Combination: Pembrolizumab, Capecitabine, and Olaparib

Abstract Introduction Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen (ER), progesterone (PR), and HER2 expression. It accounts for ∼15% of breast cancers and is more common in Black women, younger patients, and those with BRCA1 mutations. TNBC carries a poor prognosis with 5-year survival rates of 92% (localized), 66.8% (regional), and 14.3% (metastatic). Patients with high-risk of recurrence can be treated with different adjuvant therapies based on results of 3 trials (capecitabine, pembrolizumab, olaparib), but data on adverse events (AE) on their combination is limited.High-risk, stage II-III TNBC is treated with curative intent using neoadjuvant chemotherapy with pembrolizumab, followed by surgery and radiation. Pembrolizumab, an anti-PD-1 checkpoint inhibitor, was FDA-approved in 2021 based on KEYNOTE-522. This phase III trial showed that pembrolizumab plus chemotherapy significantly improved pathologic complete response (pCR) and event-free survival (EFS). 3-year EFS was 84.5% vs. 76.8% with placebo (HR 0.63); 5-year follow-up confirmed sustained benefit, with OS of 86.6%. Patients achieving pCR had better outcomes, while those with residual disease remained at high risk for recurrence, justifying further adjuvant therapy.In KEYNOTE-522, grade ≥3 treatment-related (AEs occurred in 77.1% receiving pembrolizumab-chemotherapy vs. 73.3% with placebo-chemotherapy. Pembrolizumab was linked to more serious AEs (34.1% vs. 20.1%) and higher discontinuation rates (23.3% vs. 12.3%). Before pembrolizumab, capecitabine was standard of care for TNBC with residual disease, based on the CREATE-X trial (HR 0.52 for OS benefit). Common AEs included hand-foot syndrome, fatigue, and liver enzyme elevation. Notably, KEYNOTE-522 excluded adjuvant capecitabine, and CREATE-X predated the use of pembrolizumab. Olaparib, a PARP inhibitor, was FDA-approved in 2022 for high-risk early TNBC with germline BRCA mutations, based on OlympiA. It improved invasive disease-free and OS. Grade ≥3 AEs included anemia, neutropenia, and fatigue. OlympiA did not include pembrolizumab or capecitabine, limiting insight into optimal sequencing or combination. Currently, no trials compare pembrolizumab, capecitabine, or olaparib directly, nor do they guide how to sequence or combine these therapies. Despite NCCN guidelines allowing combined/sequential use in high-risk patients, real-world safety and outcome data are lacking. This study aims to evaluate and compare the safety and effectiveness of capecitabine, olaparib, pembrolizumab, and their combinations. We will describe AE rates, onset, discontinuation, and dose modifications to inform clinical management and help reduce early termination of effective therapies. Methods We conducted a retrospective observational study across all Mayo Clinic sites. Eligible patients were ≥18 years with early-stage TNBC who initiated adjuvant therapy with capecitabine, pembrolizumab, olaparib, or combinations (capecitabine + pembrolizumab or olaparib + pembrolizumab) from October 2018 to September 2024. Patients with metastatic disease, other active malignancies, or receiving concurrent investigational therapy were excluded. The primary outcomes were incidence and timing of treatment-related AEs. Secondary outcomes included time to AE resolution, immune-related AEs, treatment interruptions/modifications, early discontinuation, and EFS. Time-to-event data will be analyzed using Kaplan-Meier and Cox proportional hazards models. Subgroup analyses by age, DPYD status, regimen, and dosing will be conducted. Data was abstracted from electronic health records and managed using REDCap. Results Data collection is completed. Final analyses are being conducted, and results will be presented at SABCS 2025. Citation Format: R. Garza-Morales, F. Raheem, D. Alton, S. Sharma, B. Murad, W. Harris, E. Terwilliger, F. Batalini. Analysis of Adverse Events and Outcomes of Adjuvant Therapies in TNBC as Monotherapy and Combination: Pembrolizumab, Capecitabine, and Olaparib 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 PS4-10-06.