2019 ASCO Annual Meeting!
Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)
Type: Poster Session
Time: Saturday June 1, 8:00 AM to 11:00 AM
Location: Hall A
Effects of immune architecture on response to adjuvant capecitabine in triple-negative breast cancer (FinXX trial).
Developmental Therapeutics and Tumor Biology (Nonimmuno)
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #134)
J Clin Oncol 37, 2019 (suppl; abstr 3142)
Author(s): Saranya Chumsri, Karama Asleh, Heather Ann Brauer, Douglas Hinerfeld, Jennifer M. Kachergus, Susanna Lauttia, Henrik Lindman, Torsten Nielsen, Heikki Joensuu, E. Aubrey Thompson; Mayo Clinic, Jacksonville, FL; The University of British Columbia, Vancouver, BC, Canada; NanoString Technologies, Inc., Seattle, WA; Nanostring Technologies, Seattle, WA; University of Helsinki, Helsinki, Finland; Uppsala University Hospital, Uppsala, Sweden; University of British Columbia, Vancouver, BC, Canada; Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
Background: Recent studies have demonstrated a benefit of adjuvant capecitabine, particularly in triple negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy. However, biomarkers to predict which patients are more likely to benefit from capecitabine are needed. Methods: The nanoString Breast Cancer 360 (BC360) and PanCancer Immunoncology (IO360) panels were used to quantify mRNA expression in TNBC samples in the FinXX trial. FinXX is a phase III trial which randomized high risk patients to receive either 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (Arm A: T+CEF) vs. 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (Arm B: TX+CEX). Gene signature scores were analyzed using prespecified algorithms developed by nanoString. Digital Spatial Profiling was carried out using GeoMX platform. Results: A total of 111 TNBC patients in FinXX trial were included (57 in Arm A and 54 in Arm B) with 10.2 years median follow up. There were 7 cancer- and immune-related gene signatures identified by BC360 and IO360 panels that were significantly associated with improved recurrent free survival favoring an addition of capecitabine. These include cytotoxic cell signature (HR 0.37, 95%CI 0.15-0.92, p 0.03), endothelial signature (HR 0.18, 95%CI 0.04-0.83, p 0.03), mast cell signature (HR 0.43, 95%CI 0.21-0.88, p 0.02), PDL2 gene (HR 0.29, 95%CI 0.09-0.99, p 0.05), immunoproteasome (HR 0.34, 95%CI 0.13-0.89, p 0.02), exhausted CD8 (HR 0.29, 95%CI 0.09-0.97, p 0.04), and PD1 (HR 0.44, 95%CI 0.20-1.02, p 0.05). Conclusions: Analysis of RNA abundance signatures strongly suggests that there are important immune features that are associated with benefit from capecitabine in TNBC. However, analysis of RNA extracted from whole tumor sections lacks spatial discrimination. We anticipate that a more detailed, spatially-defined analysis of protein abundance, using the novel NanoString GeoMX platform, will provide more insights and define specific immune features associated with improved outcome. Additional results of GeoMX will be reported at the meeting. Clinical trial information: NCT00114816