RT Journal Article
T1 Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial.
A1 Powles, Thomas
A1 Kockx, Mark
A1 Rodriguez-Vida, Alejo
A1 Duran, Ignacio
A1 Crabb, Simon J
A1 Van-Der-Heijden, Michiel S
A1 Szabados, Bernadett
A1 Pous, Albert Font
A1 Gravis, Gwenaelle
A1 Herranz, Urbano Anido
A1 Protheroe, Andrew
A1 Ravaud, Alain
A1 Maillet, Denis
A1 Mendez, Maria Jose
A1 Suarez, Cristina
A1 Linch, Mark
A1 Prendergast, Aaron
A1 van-Dam, Pieter-Jan
A1 Stanoeva, Diana
A1 Daelemans, Sofie
A1 Mariathasan, Sanjeev
A1 Tea, Joy S
A1 Mousa, Kelly
A1 Banchereau, Romain
A1 Castellano, Daniel
K1 Predictive markers
K1 Bladder cancer
AB Antibodies targeting PD-1 or its ligand 1 PD-L1 such as atezolizumab, have great efficacy in a proportion of metastatic urothelial cancers1,2. Biomarkers may facilitate identification of these responding tumors3. Neoadjuvant use of these agents is associated with pathological complete response in a spectrum of tumors, including urothelial cancer4-7. Sequential tissue sampling from these studies allowed for detailed on-treatment biomarker analysis. Here, we present a single-arm phase 2 study, investigating two cycles of atezolizumab before cystectomy in 95 patients with muscle-invasive urothelial cancer (ClinicalTrials.gov identifier: NCT02662309). Pathological complete response was the primary endpoint. Secondary endpoints focused on safety, relapse-free survival and biomarker analysis. The pathological complete response rate was 31% (95% confidence interval: 21-41%), achieving the primary efficacy endpoint. Baseline biomarkers showed that the presence of preexisting activated T cells was more prominent than expected and correlated with outcome. Other established biomarkers, such as tumor mutational burden, did not predict outcome, differentiating this from the metastatic setting. Dynamic changes to gene expression signatures and protein biomarkers occurred with therapy, whereas changes in DNA alterations with treatment were uncommon. Responding tumors showed predominant expression of genes related to tissue repair after treatment, making tumor biomarker interpretation challenging in this group. Stromal factors such as transforming growth factor-β and fibroblast activation protein were linked to resistance, as was high expression of cell cycle gene signatures after treatment.
PB Nature Publishing Group
YR 2019
FD 2019-11-04
LK http://hdl.handle.net/10668/14633
UL http://hdl.handle.net/10668/14633
LA en
NO Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706-1714.
DS RISalud
RD Apr 19, 2025