Abstract PS4-07-03: Adverse Events in Neoadjuvant Therapy for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis of Phase III Trials

Abstract Background: Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers and lacks expression of estrogen receptor, progesterone receptor, and HER2, limiting targeted options. Recent neoadjuvant therapy (NAT) advances include immune checkpoint inhibitors (ICIs) and PARP inhibitors, improving pathologic complete response (pCR) and survival but raising concerns about severe toxicity. Despite broader adoption of these regimens, a systematic analysis of Grade ≥3 adverse events (AEs) from contemporary phase III trials is lacking. Methods: We conducted a PRISMA-guided systematic review and meta-analysis (PROSPERO: CRD42024562785). MEDLINE, Embase, and Cochrane were searched for phase III randomized trials (Jan 2010-Jun 2025) evaluating NAT in non-metastatic TNBC and reporting Grade ≥3 AEs (CTCAE). One phase II trial (WSG-ADAPT-TN; n=336) with robust comparative design and AE reporting was also included. Pooled prevalence and risk ratios (RR) with 95% CI were calculated using DerSimonian-Laird random-effects models. Subgroup analyses included: Group A (PARP inhibitors), B (immunotherapy), and C (platinum-based regimens). Heterogeneity was assessed via I2. Results: Six trials with 3,316 TNBC patients were included (BrighTNess, IMpassion031, KEYNOTE-522, NeoTRIP, PARTNER, WSG-ADAPT-TN). Neutropenia was the most common Grade ≥3 AE, highest with immunotherapy (33.5%), followed by PARP inhibitors (23.7%) and platinum regimens (16.0%) (Q=71.8, p<0.0001). PARP inhibitors significantly increased neutropenia risk (RR=1.84), while immunotherapy showed no increase (RR=1.00, p=0.94). Grade ≥3 anemia was higher with PARP inhibitors (20.6%) vs. immunotherapy (9.9%), with doubled risk vs. placebo (RR=2.08, p=0.02). Thrombocytopenia was most prevalent with immunotherapy (7.9%), but PARP inhibitors showed the highest risk (RR=3.56, p=0.0001). Febrile neutropenia was more common with ICIs (14.9%) than PARP inhibitors (3.0%). ALT elevation was more frequent in platinum regimens (6.4%), without significant differences across groups. Fatal AEs were <1% in all trials. Conclusions: Modern NAT regimens improve outcomes in TNBC but confer significant Grade ≥3 toxicity. PARP inhibitors pose the highest hematologic risk, while ICIs increase febrile neutropenia. Platinum regimens showed the most favorable toxicity profile. Findings highlight the need for biomarker-driven, individualized treatment and vigilant AE monitoring in early TNBC. Citation Format: M. Antonini, A. Mattar, F. P. Cavalcante, F. P. Zerwes, E. C. Millen, F. P. Brenelli, A. L. Frasson, M. D. Teixeira, M. Madeira, G. Facina, H. L. Couto, G. T. Tosello, R. Arakelian, A. D. Lima, G. N. Garcia, F. Bagnoli, A. G. Amorim, M. F. de Figueiredo, L. R. Soares, R. Freitas Júnior, L. H. Gebrim. Adverse Events in Neoadjuvant Therapy for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis of Phase III Trials [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 PS4-07-03.