2018 ASCO Annual Meeting!
Session: Tumor Biology
Type: Poster Session
Time: Monday June 4, 1:15 PM to 4:45 PM
Location: Hall A
Role of serum thymidine kinase-1 (TK1) activity in patients (pts) with hormone receptor positive (HR+) advanced breast cancer (ABC) treated with endocrine therapy (ET) in the EFECT trial.
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #144)
J Clin Oncol 36, 2018 (suppl; abstr 12031)
Author(s): Luca Malorni, Chiara Biagioni, Amelia McCartney, Gaia Schiavon, Mattias Bergqvist, Matteo Benelli, Ilenia Migliaccio, Laura Biganzoli, Martina Bonechi, Giulia Boccalini, Marta Pestrin, Francesca Galardi, Francesca De Luca, Martine J. Piccart-Gebhart, William John Gradishar, Stephen K. L. Chia, Angelo Di Leo; Sandro Pitigliani Medical Oncology Department, Hospital of Prato, Prato, Italy; Bioinformatics Unit, Hospital of Prato, Prato, Italy; IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom; Biovica International, Uppsala, SE; Sandro Pitigliani Translational Research Unit, Hospital of Prato, Prato, Italy; Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Northwestern University, Chicago, IL; BC Cancer Agency, Vancouver, BC, Canada
Background: TK1 plays a critical role in DNA synthesis and cell proliferation. The DiviTum assay measures serum TK1 activity (sTKa), reflecting cancer cell proliferation. Recent studies suggest this assay may provide real time prognostic information in ABC. However, its role in HR+ ABC needs further validation. Methods: EFECT (n = 693) was a double-blind, randomized trial of fulvestrant 250mg versus exemestane after progression on nonsteroidal aromatase inhibitor therapy for ABC. 58% of pts had received > 1 prior ET for ABC. sTKa was retrospectively assessed with DiviTum on serum samples from pts in the EFECT cohort. Samples were collected before start of ET (T0), after 3 (T3) and 6 (T6) months of ET, and at disease progression (PD). Pts were categorized as High/Low sTKa at T0 based on the median value. On-treatment sTKa changes were calculated from T0 to the next available time-point within 3 months from randomization (T3, or PD for those pts with early progression - ePD), accounting for a coefficient of variation of 10%, and defined as follows: Drop (T3 or ePD < T0); Increase (T3 or ePD > T0); No change (T3 or ePD = T0). Analyses were conducted regardless of study arms. Results: All available samples were successfully tested for sTKa (586 samples from 244 consenting pts). Median sTKa at T0 (n = 227), T3 (n = 135), T6 (n = 80) and PD (n = 137) was 97, 57, 57.5 and 132 Du/L, respectively. Median time to progression (mTTP) for pts with Low T0 sTKa (n = 111) was 5.03 months (m) (95% CI 3.91-5.89) vs 2.57 (95% CI 2.04-3.52) for pts with High T0 sTKa (n = 110) (p < 0.001). On-treatment sTKa changes from T0 were analysed in 159 pts (T3 = 116; ePD = 43). mTTP in pts with TK1 Drop (n = 53) was 5.4 m (95% CI 3.7-7.7) vs 3.4 (95% CI 2.1-4.1) in pts with Increase (n = 68) (p < 0.018). mTTP in pts with No change (n = 38) was similar to those with Drop. After adjustment for major prognostic factors, sTKa remained an independent marker. Conclusions: sTKa is a potential circulating prognostic marker in pts with ABC treated with ET, and may represent a tool for upfront identification of ET-resistant pts, and non-invasive monitoring of response to ET. Independent validation of these results is warranted.