Comprehensive analysis of TROP2, PD-L1, stromal (s)TILs, and HER2 expression patterns in patients (pts) with metastatic HR+HER2- breast cancer

• Published in: Journal of clinical oncology Vol. 42; no. 16_suppl; p. 1062
• Main Authors: Heiling, Hillary, Hughes, Melissa E., Binboğa Kurt, Busem, DiLullo, Molly, Li, Tianyu, Tayob, Nabihah, Curigliano, Giuseppe, Mittendorf, Elizabeth A., Lin, Nancy U., Tolaney, Sara M., Garrido-Castro, Ana Christina
• Format: Journal Article
• Language: English
• Published: American Society of Clinical Oncology 01.06.2024
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2024.42.16_suppl.1062

1062Background: Immune checkpoint inhibitors (ICI) have shown limited efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC) and the optimal ICI-based combination is unknown. The TROP2 antibody-drug conjugate sacituzumab govitecan (SG) demonstrated antitumor activity with a 5.5-month median PFS in endocrine refractory HR+ mBC. Given SG's potential for anticancer immunity, we sought to evaluate expression patterns of biomarkers of interest in HR+ mBC. Methods: This retrospective study included pts with HR+HER2- mBC identified at DFCI between 10/2020 and 12/2021 who received 0-1 prior lines of chemotherapy in the metastatic setting and consented to analysis of archival FFPE tissue samples. We aimed to 1) characterize expression patterns of TROP2 (SP295 H-score), PD-L1 (22C3 CPS), sTILs and HER2 (per central pathology review) in the most recent available sample; 2) assess the prognostic value of selected biomarker combinations for overall survival (OS) defined as the time from consent to either death due to any cause or last follow-up (Cox proportional hazard models; p-value <0.05 considered significant). Results: Among 142 pts included, median age at diagnosis was 46 yrs (IQR: 40-56). Baseline characteristics are shown (Table). At least one biomarker was available for 123 subjects (86.6%). TROP2 expression (n=61) was Medium/High (M-H: 101-300) in 43 pts (70.5%) and Low (L: 0-100) in 18 (29.5%). PD-L1 central assessment (n=120) revealed CPS ≥1 (PD-L1+) in 32 pts (26.7%) and <1 (PD-L1-) in 88 (73.3%); only 7 (5.8%) pts had CPS ≥10. sTILs (n=87) were ≥10% in 14 pts (16.1%) and <10% in 73 (83.9%). When analyzing TROP2 and PD-L1 (n=61), 15 pts (24.6%) were TROP2-M-H/PD-L1+, 28 (45.9%) were TROP2-M-H/PD-L1-, 5 (8.2%) were TROP2-L/PD-L1+, and 13 (21.3%) were TROP2-L/PD-L1-. When analyzing TROP2 and sTILs (n=54), 6 pts (11.1%) were TROP2-M-H/sTILs ≥10%, 32 (59.3%) were TROP2-M-H/sTILs <10%, 2 (3.7%) were TROP2-L/sTILs ≥10% and 14 (25.9%) were TROP2-L/sTILs <10%. For TROP2 and HER2 (n=46), 26 pts (56.5%) had TROP2-M-H/HER2-low tumors, 7 (15.2%) TROP2-M-H/HER2-0, 3 (6.5%) TROP2-L/HER2-low, and 10 (21.7%) TROP2-Low/HER2-0. Median OS (n=138) was 43.8 months; stratification for selected biomarker combinations will be presented although no statistical significance was found. Correlations with NGS data and HER2DX are ongoing and will be presented. Conclusions: Analyzing biomarkers of interest in pts with HR+ mBC unveiled diverse patterns, without associations with OS. Patient characteristics. CharacteristicPatients (N = 142)Recurrent mBC, n. (%)113 (79.6)De novo stage IV, n. (%)27 (19.0)N/A, n. (%)2 (1.4)Known germline mutation (any), n. (%)20 (14.1)Prior chemotherapy (metastatic), n. (%)58 (40.8)Median number of prior lines of ET (metastatic) n. (IQR)1 (1 - 2)HER2-0, n. (%)31 (21.8)HER2-low, n. (%)46 (32.4)N/A, n. (%)65 (45.8)