Abstract PS5-03-06: Real-world progression-free survival from first-line treatment initiation in patients with PD-L1-negative locally recurrent inoperable or metastatic triple-negative breast cancer in the United States

Abstract Background: Patients with PD-L1-negative locally recurrent inoperable or metastatic triple-negative breast cancer (lr/m TNBC) have limited treatment options and typically receive first-line (1L) chemotherapy in clinical practice. Real-world evidence on patient outcomes, particularly real-world progression-free survival (rwPFS) from 1L treatment initiation in PD-L1-negative lr/m TNBC, remains scarce. Additional data are needed to better understand clinical outcomes in this population and support evidence-based treatment decision-making. Methods: A retrospective cohort of adults (≥18 years old) receiving 1L treatment for PD-L1-negative lr/m TNBC was identified in Komodo Research Data (01/2016-12/2023), a large claims database that covers approximately 30% of the United States (US) population. Patients with lr/m TNBC were identified using an algorithm developed with medical expert guidance that required systemic treatment initiation within 3 months of a biopsy and no observed surgery in the 12 months following the biopsy. Triple-negative and PD-L1 statuses were inferred from treatments received in the lr/m setting. Demographics were described on the date of 1L treatment initiation, and comorbidities were assessed during the preceding 12 months. Real-world proxies of progression were also defined with medical expert guidance and included death, hospice admission, initiation of a second line of systemic treatment, or initiation of radiotherapy. Among patients who initiated 1L treatment ≥6 months before the end of data availability, the Kaplan-Meier method assessed rwPFS from 1L treatment initiation until the first real-world proxy of progression or end of follow-up, defined as the earliest of end of continuous health plan enrollment or end of data availability. Results: A total of 929 patients with lr/m TNBC were identified in this study. The median (interquartile range IQR) age at 1L initiation was 59 (51-66) years. Most patients were female (98.6%). Among those with a recorded race (69.3%), 60.1% were White, 26.4% were Black or African American, and 9.2% were Hispanic or Latino. Most patients had commercial insurance (64.9%), followed by Medicare (26.7%) and Medicaid (8.4%). The most frequent comorbidities prior to 1L treatment initiation were liver disease (26.8%), chronic obstructive pulmonary disease (22.7%), diabetes (22.0%), and peripheral vascular disease (13.6%). Median (IQR) follow-up from 1L initiation was 10.3 (5.7-20.1) months. The most common 1L treatments in the lr/m TNBC setting included cyclophosphamide+doxorubicin-based regimens (28.1%), followed by capecitabine (12.7%), paclitaxel (10.4%), carboplatin+paclitaxel (9.4%), and carboplatin+gemcitabine (8.6%), with frequent use of non-NCCN-guideline-preferred regimens. Among the 910 patients with sufficient follow-up to assess rwPFS, 703 (77.3%) had an indicator of progression following 1L initiation. Median (95% confidence interval CI) rwPFS was 4.7 (4.5-5.2) months. rwPFS rates (95% CI) were 69.0% (65.9%-71.9%) at 3 months, 41.7% (38.4%-45.0%) at 6 months, 22.6% (19.7%-25.6%) at 12 months, and 18.3% (15.5%-21.2%) at 18 months. The observed indicators of progression were, in order of frequency, initiation of a second line of systemic treatment (43.8%), death (25.5%), initiation of radiotherapy (18.1%), and hospice admission (12.7%). Conclusions: In US clinical practice, patients with PD-L1-negative lr/m TNBC experience rapid disease progression following initiation of 1L treatment, with a median time to progression of less than 5 months. These findings underscore a critical unmet need for effective 1L treatment options with tolerable safety profiles to improve outcomes in this patient population. Citation Format: T. A. Traina, E. Serra, J. Bedard, M. Levesque-Leroux, P. Gagnon-Sanschagrin, A. Guérin, S. Guenther, G. Joseph, V. Guan, J. Salcedo. Real-world progression-free survival from first-line treatment initiation in patients with PD-L1-negative locally recurrent inoperable or metastatic triple-negative breast cancer in the United States 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 PS5-03-06.