Abstract PS4-07-29: Evaluating the tolerability of the combination of adjuvant pembrolizumab and capecitabine in a diverse real-world cohort of patients with early-stage TNBC

Abstract Background: Although the KEYNOTE-522 trial demonstrated a significant pCR following neoadjuvant chemoimmunotherapy, 35.2% of patients had evidence of residual disease following surgery, a population who may be recommended to receive adjuvant capecitabine per the CREATE-X trial. However, there is a paucity of real-world data evaluating the tolerability of adjuvant pembrolizumab, per KEYNOTE-522, when combined with adjuvant capecitabine, per CREATE-X. Our study examines the tolerability of the adjuvant combination in a real-world, diverse, urban population at a large tertiary referral center. Methods: We performed a retrospective chart review of patients (pts) with stage II-III TNBC who received the KEYNOTE-522 regimen within our institution’s health system from August 2021 to February 2025. Pts who received /= 1 cycle of adjuvant pembrolizumab were included in our analysis. Pts were stratified based on receipt of adjuvant pembrolizumab alone versus combination of pembrolizumab and capecitabine. Demographics, adjuvant toxicity data including rates of treatment delays, dose holds, and treatment discontinuations were extracted from the medical record. Descriptive statistics were used to describe patient data, and non-parametric tests were utilized in the stratified analyses. Due to the exploratory nature of our analysis, p-values are reported unadjusted. Results: 83 pts received adjuvant pembrolizumab and were included in this analysis. Overall, 64% (N=53) were on adjuvant pembrolizumab alone and 36% (N=30) on the combination of adjuvant pembrolizumab and capecitabine. Overall, 83% had Stage II disease and 45% with lymph node involvement. 28% of pts (N=23) identified as White, 28% (N=23) Black, 16% (N=13) Asian, 19% (N=16) Hispanic, and 9% (N=8) as Other. The early discontinuation rates (prior to 9 cycles) of adjuvant pembrolizumab in the pembrolizumab cohort and combination cohort were 17% (N=9) and 13% (N=4), respectively (p=0.761). Pembrolizumab was discontinued most frequently due to irAEs including thyroiditis, colitis, pneumonitis and myocarditis. In the combination cohort of 30 pts, 47% (N=14) required a capecitabine dose reduction, 27% (N=8) required a dose hold, and 30% (N=9) discontinued capecitabine prior to 6 cycles (Table 1). Capecitabine was dose reduced or held most frequently for non-hematologic reasons including hand-foot syndrome, GI toxicity, and mucositis. Conclusion: The adjuvant combination of capecitabine and pembrolizumab appeared to be well tolerated. Treatment was held, dose reduced or discontinued more commonly from known side effects of capecitabine or pembrolizumab, but not as the result of worsening toxicity from combination therapy. Overall, the combination of capecitabine and pembrolizumab warrants further study for pts with residual disease after neoadjuvant KEYNOTE-522. Citation Format: J. Anderson, E. Baldwin, J. Dejesus, G. Van Hyfte, P. Pandu, N. Krishnamurthy, M. Rattu, R. Farley, R. Patel, A. Tiersten. Evaluating the tolerability of the combination of adjuvant pembrolizumab and capecitabine in a diverse real-world cohort of patients with early-stage TNBC 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 PS4-07-29.