Abstract P2-01-21: Baseline circulating tumor cells (CTCs) predict for progression-free survival (PFS) after ablation on NRG-BR002, a randomized phase II/III study of ablation vs. standard systemic therapy care (SOC) for oligometastatic breast cancer (OMBC)

Background: NRG-BR002 randomized patients with OMBC to SOC with vs. without ablation (surgery or radiation) of all visible metastases. The phase II PFS go signal for improvement with ablation was not met. Blood for CTCs was collected from consenting patients and sent for the FDA-approved CellSearch CTC assay and High-Definition Single Cell CTC Analysis (HDSCA). The primary CTC objective was that pretreatment CTCs (PreRX CTCs) would be prognostic for PFS. Secondary objectives included baseline CTCs being predictive for the effect of RX on PFS and CTC post-treatment clearance rate correlating with PFS. Statistical Design and Methods: A secondary endpoint analysis of the prognostic effect of PreRX CTCs on PFS and the interaction between study arm and the PreRX CTCs on PFS were evaluated for both assays using multivariable Cox proportional hazards models (MVA). CellSearch CTCs were dichotomized 0 vs. ≥ 1 and HDSCA CTCs were assessed by < vs. ≥ lowest quartile (Q1). Due to small numbers of CTC+ cases, CTC clearance correlation with PFS was not able to be tested. Descriptive results are presented. Results: Of 125 phase II eligible patients, 108 (86%) consented to blood collection. Among the cohort with CTC data (n=62 for CellSearch, n=60 for HDSCA), demographic and treatment variables were balanced between study arms and similar to the trial population. Thirty-six (58%) and 26 (42%) had CellSearch CTC = 0 and ≥1, respectively. Fifteen (25%) and 45 (75%) had HDSCA CTCs < Q1 and ≥ Q1, respectively. Median follow up at the time of analysis was 48 months. PreRX CTCs (CellSearch and HDSCA) were not prognostic for PFS. In each of the analyses for PreRX CTC (0 or < Q1) being predictive for PFS, after adjusting for number of metastases (1 v >1), the interaction between study arm and CTCs had a HR > 3, reaching statistical significance for HDSCA (p=0.024; HR 5.58, 95% CI: 1.26, 24.77) and trending towards statistical significance for CellSearch (p=0.063; HR 3.39, 95% CI: 0.94, 12.25). Patients in the ablation arm, with HDSCA PreRX CTCs < Q1, experienced better PFS than those with PreRX CTCs ≥ Q1; 78% vs. 33% at 2 years, respectively, as compared to patients on the control arm (17% vs. 55%). Patients in the ablation arm, with CellSearch PreRX CTCs = 0, also experienced better PFS than those with PreRX CTCs ≥ 1; 54% vs. 27% at 2 years, respectively, as compared to patients on the control arm (35% vs. 61%). For CellSearch only, 19/62 patients (9 SOC and 10 ablation) had positive PreRX and PostRX CTC values. In the SOC arm, clearance of CTCs was seen in 6 patients (all progression-free) and no clearance in 3 (2 progressed/1 died). In the ablation arm, clearance (n=5)/decrease (n=2) of CTCs was seen in 7 patients; however, only 3 remained progression-free; and an increase was seen in 3 patients whose disease progressed. For the 9 patients across both arms with PreRX and PostRX CTCs that progressed, all 9 developed new metastatic sites. Conclusion: Lower PreRX CTCs predicted for improved PFS after ablation using the HDSCA assay. The pre-specified CTC analyses provide consistent results using two independent assays highlighting the robustness of the finding. These hypothesis-generating findings suggest that PFS is improved in CTC negative OMBC patients who are treated with ablation. This project was supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), BCRF-23-089, U01CA285013 (LBRL), and U24CA180803 (IROC) from the National Cancer Institute (NCI).Citation Format: Wendy Woodward, Jennifer Moughan, Steven Chmura, Peter Kuhn, Anthony Lucci, Virginia F Borges, Joseph K Salama, Hania Al-Hallaq, Martha M Matuszak, Michael T Milano, Nora Jaskowiak, Stephanie N Shishido, Jeremy Mason, Salyna Meas, Carol Hall, Sachin R Jhawar, Robert A Nordal, Gregory N Gan, Diane C Ling, Imran Zoberi, Sobha Kurian, Kathryn Winter, Eleftherios P Mamounas, , Julia R White. Baseline circulating tumor cells (CTCs) predict for progression-free survival (PFS) after ablation on NRG-BR002, a randomized phase II/III study of ablation vs. standard systemic therapy care (SOC) for oligometastatic breast cancer (OMBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-01-21.

Duke Scholars

Author Joseph Kamel Salama Radiation Oncology