Abstract RF4-06: FDG-PET to assess therapeutic response in patients with bone-dominant metastatic breast cancer, FEATURE: ECOG-ACRIN EA1183

Abstract Background: Patients (pts) with bone-only (BO) or bone-dominant (BD) metastatic breast cancer (MBC) represent a large patient population who are often excluded from clinical trials using RECIST 1.1 as the primary response assessment because bone lesions are classified as non-measurable, non-target lesions. FDG-PET/CT provides a direct measure of tumor metabolic activity, and we hypothesized that categories of metabolic response assessed by FDG-PET/CT will be predictive of important clinical endpoints: progression free survival (PFS), time to skeletal related events (SRE), and overall survival (OS). Methods: Pts with hormone receptor positive MBC, known HER2 status, and radiologically confirmed BD or BO disease receiving systemic therapy for MBC were eligible for the study. Pts underwent a baseline FDG-PET/CT scan (T0) then started systemic therapy within 21 days of the T0 scan. Pts underwent a second FDG-PET/CT scan 12 wks after initiating therapy (T1). Response assessment by serial FDG-PET/CT was completed using mPERCIST criteria (where measurable lesions on the T0 scan were defined as having SULpeak greater than 1.5 × mean liver SUL). Change in SULpeak was calculated as the percentage change in SULpeak of the single hottest lesion at the T0 scan and the single hottest lesion at the T1 scan. Pts responses were classified as mPERCIST responders (complete metabolic response, partial metabolic response, or stable metabolic disease) or non-responders (progressive metabolic disease [PMD]). Unequivocal progression was defined as progressive disease (PD) per RECIST 1.1 (with some modifications related to the MD Anderson criteria for bone metastases for non-measurable disease) or death from any cause. To determine PD, pts were followed serially with standard-of-care imaging at 12-wk intervals for five intervals following therapy initiation, and at 24-wk intervals thereafter. Following disease progression, pts continued to be followed every 6 months to assess vital status and SRE. Results: 138 pts were enrolled at 35 NCTN/NCORP sites. After enrollment, 1 pt was deemed ineligible due to pleural effusion seen on the pre-enrollment CT scan. Of the 137 eligible pts, 2 pts did not undergo the T0 FDG-PET/CT scan, 1 pt did not start systemic therapy, 7 pts did not have a T1 FDG-PET/CT scan, and 11 pts did not have an evaluable mPERCIST response due to absence of measurable lesions on T0. Hence, the analysis set consists of 116 pts. The median age was 59.5 (IQR: 51.5-66) years. 72.4% (84/116) of pts identified as White and 9.5% (11/116) identified as Black or African American, and 5.2% (6/116) identified as Hispanic or Latino. Of 116 mPERCIST response evaluable pts [data cutoff 1 Sep 2025; median follow-up 14.4 months (mos); (IQR: 6.2-25.9)], 21 had PMD and 95 did not have PMD. PFS was compared between pts with and without PMD. The median PFS was 3.0 mos (95% CI: 2.8 to 5.6 mos) for the PMD group and 19.4 mos (95% CI: 15.1 to 30.5 mos) for the non-PMD group (log-rank test P<0.001). Univariate Cox regression analysis yielded a hazard ratio (HR) of 0.16 (95% CI: 0.10 to 0.28; P<0.001), indicating a significantly lower risk of progression in pts with non-PMD compared to PMD pts. A multivariable Cox regression model was fit to estimate the HR of the dichotomized mPERCIST response controlling for age, menopausal status, ECOG performance, HER2 status, metastatic presentation, line of therapy, and type of therapy. The HR for the mPERCIST response was 0.17 (95% CI: 0.09 to 0.33; P<0.001), confirming a statistically significant longer PFS for mPERCIST responders versus non-responders. Conclusions: Our analysis demonstrates that the 12-wk mPERCIST response (dichotomized as PMD versus non-PMD) is significantly associated with PFS. These findings support the role of serial FDG PET/CT mPERCIST response assessment in pts with BD and BO MBC. Citation Format: J. M. Specht, F. Duan, H. Jacene, E. Q. Konnick, F. Brescia, A. R. Pantel, S. J. Galgano, J. Romanoff, L. M. Peterson, M. Muzi, N. U. Lin, A. K. Abou Hussein, W. Razaq, W. R. Gwin, A. N. Shah, M. A. Cherian, B. H. Mavromatis, C. L. Wright, D. G. Stover, A. M. Fowler, H. M. Linden, A. M. DeMichele, J. E. McConathy, C. Comstock, A. C. Wolff, D. A. Mankoff. FDG-PET to assess therapeutic response in patients with bone-dominant metastatic breast cancer, FEATURE: ECOG-ACRIN EA1183 [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 RF4-06.