Outcomes after recurrence on neoadjuvant chemo-immunotherapy (NCIT) in patients (pts) with high-risk early-stage triple-negative breast cancer (eTNBC).

601 Background: NCIT improves survival in high-risk eTNBC; however, trial-based data show that most relapses after NCIT are early. Real-world data are lacking. Methods: This retrospective study included pts from the DFCI Multicenter TNBC registry with eTNBC or estrogen receptor (ER)-low (≤10%), HER2-negative breast cancer (BC) treated with NCIT who underwent surgery before 7/1/2025. Aims were to evaluate (1) patterns of relapse; (2) BC–specific event–free survival (BC-EFS) from the first NCIT dose to relapse, contralateral BC, or death; (3) first-line (1L) metastatic systemic treatment patterns, and (4) time to progression (TTP). Results: 220 pts were identified, with median age of 50.1 yrs (IQR: 40.5-60.8). Median follow-up (FU) was 32.7 months (mo) (IQR, 30.4–34.4). At last FU, 29 pts (13.2%) had relapsed (locoregional, n=2; distant, n=27). Among these, 86.2% had not experienced pathologic complete response. Among relapsed pts with PD-L1 assessment (n=16), 43.8% (n=7) had a Combined Positive Score (CPS) <10; 56.2% (n=9) had a CPS ≥10. BC-EFS is shown in the Table. 1L therapy consisted of antibody-drug conjugate (ADC) in 51.7% (n=15), Poly ADP-ribose Polymerase inhibitor (PARPi) in 13.8% (n=4), chemotherapy in 13.8% (n=4), ADC+PARPi in 3.4% (n=1), CIT in 3.4% (n=1), and HER2-directed in 3.4% (n=1); 10.3% (n=3) died before 1L therapy. Median (m)TTP in 1L (n=26) was 7.7 mo (95% CI, 6.0–13.0) and detailed in the Table. Among pts with disease-free interval (DFI) ≤6 mo (n=8), mTTP was 5.1 mos (2.7–NR), with TTP rates of 50.0% (25.0–100.0) at 6 mo and 16.7% (2.9–95.3) at 12 mo. In those with DFI 6–12 mo (n=9), mTTP was 9.7 mo (7.4–NR); TTP rates were 88.9% (70.6–100.0) at 6 mo and 25.4% (7.7–83.8) at 12 mo. For DFI >12 mo (n=9), mTTP was 8.6 mo (5.6–NR), with TTP rates of 71.4% (44.7–100.0) at 6 mo and 28.6% (8.9–92.2) at 12 mo. Among pts treated with 1L ADC (n=16), mTTP was 8.6 mo (7.4–NR); TTP rates were 77.9% (58.4–100.0) at 6 mo and 26.0% (9.9–68.3) at 12 mo. In non-ADC-treated pts (n=10), mTTP was 6.2 mo (3.78–NR), with TTP rates of 60.0% (36.2–99.5) at 6 mo and 20.0% (5.8–69.1) at 12 mo. Median overall survival (from diagnosis) among pts with relapse was 26.3 mo (95% CI, 25.0–NR). Conclusions: Relapse after NCIT was predominantly early with poor metastatic outcomes, underscoring an urgent need for new strategies in this population largely excluded from clinical trials. Any NCIT(n = 216) KEYNOTE-522(n = 176) 1L for metastatic TNBC(n = 26) Time from NCIT start (mo) BC-EFS % (95% CI) Event N BC-EFS % (95% CI) Event N Time from 1L start (mo) TTP survival % (95% CI) Event N 6 100.0(100.0, 100.0) 0 100.0(100.0, 100.0) 0 6 70.8(54.6, 91.7) 7 12 95.4(92.5, 98.4) 9 95.0(91.7, 98.4) 8 12 23.6(11.0, 50.5) 17 18 89.4(84.9, 94.0) 19 89.7(84.9, 94.8) 15 18 14.2(5.0, 40.3) 19 24 86.4(81.3, 91.8) 23 86.0(80.3, 92.2) 19 24 9.4(2.5, 35.2) 20 36 79.9(72.2, 88.3) 27 82.2(74.8, 90.3) 21