Trends in immunotherapy use and survival outcomes by metastatic pattern in metastatic triple-negative breast cancer.

1127 Background: KEYNOTE-355 demonstrated that adding pembrolizumab to chemotherapy improved progression-free and overall survival (OS) vs chemotherapy alone in patients with metastatic TNBC (mTNBC) and PD-L1 CPS ≥10. Approved in 2020, this regimen transformed advanced TNBC management. However, the benefit of immunotherapy (IO) according to metastatic site remains underexplored given the varied immune environments between organs, with the liver being particularly immune-suppressed. Methods: We conducted a retrospective analysis of 2022 NCDB data for female patients diagnosed 2016–2021 with de novo mTNBC. OS was defined as months from diagnosis to death/last contact. Patients were stratified by first-line therapy (chemotherapy alone vs chemotherapy + IO) and metastatic pattern (isolated liver/lung/bone/brain; multiple sites). IO type was not specified. P-values were calculated by chi-squared/Fisher’s exact tests as appropriate. Hazard ratios (HR) were estimated by a univariate Cox model. Results: 2329 patients with de novo mTNBC were included in our study. Median age was 59 years, median follow-up time was 42 months. 1723 (74%) received chemotherapy alone and 606 (26%) received chemotherapy + IO. The proportion of patients receiving IO increased each year between 2016 and 2021 (3.3% - 34.3%). Overall, patients treated with chemotherapy + IO had better OS compared to chemotherapy alone (HR = 0.58, 95% CI, 0.51-0.65, P<0.001). Isolated lung metastasis was the most common pattern (n=402, 20.9%), followed by bone (n=374, 19.4%), liver (n=246, 12.8%), and brain metastasis (n=14 , 0.7%). 892 (46.3%) patients had multiple metastatic sites. Patients with isolated lung, liver or bone metastases had better OS vs those with multiple metastatic sites (lung, HR 0.54, 95% CI 0.47–0.62; liver, HR 0.62, 95% CI 0.53-0.73; bone, HR 0.69, 95% CI 0.60–0.79). Kaplan–Meier analysis showed superior OS with chemotherapy + IO vs chemotherapy alone across lung, liver, bone, and multiple metastases subgroups (log-rank P<0.0001, P=0.0003, P=0.0017, P<0.0001, respectively); brain metastasis analysis limited by small sample size (Table 1). Conclusions: In this large real-world mTNBC cohort, IO adoption increased post-KEYNOTE-355 approval and associated with an overall 42% lower mortality risk vs chemotherapy alone. Additionally, increased IO adoption correlated with increased survival over time. The survival benefit of IO was preserved across different metastatic sites of disease. Overall survival in mTNBC patients by metastatic site and treatment modality. Met site Treatment N Median survival, months 24-mo survival, % 36-mo survival, % Lung Chemo + IO 57 32.1 60.6 49.4 Chemo 220 15.9 38 24.8 Liver Chemo + IO 47 27.7 52.4 37.7 Chemo 141 15.5 33.4 18.7 Bone Chemo + IO 67 23.5 49.2 26.3 Chemo 221 13.2 29.7 19.8 Multiple Chemo + IO 155 16.4 36.3 26.4 Chemo 593 8.7 18.1 10.3