Abstract 5877
Background
Immunotherapy (IO) with antibodies against PD1 or PD-L1 has been approved for 1st and 2nd line treatment of metastasized urothelial bladder cancer (mUC). Here we evaluated efficacy in a retrospective Real-World-Phase IV trial based on molecular subtypes and PD-L1 status.
Methods
Cancer specific survival from start of IO treatment to death was retrospectively analyzed in a multicenter cohort of 65 patients having received palliative immune checkpoint inhibition for mUC in 1st and 2nd line setting. Intrinsic molecular subtypes were assessed by CK5, CK20, GATA3, FOXA1 and CD44 immunohistochemistry and RT-qPCR of KRT5 and KRT20. PD-L1 status was determined using the 28-8 Dako-assay. Stromal tumor infiltrating lymphocytes were assessed on HE slides (Salgado et al, 2015). Survival analyses were performed by applying clinically relevant cut-offs and using Kaplan-Meier analysis and logistic regression for cancer specific survival (CSS).
Results
Altogether, 43% of tumors presented with basal differentiation, 57% were luminal. As expected, basal tumors exhibited significantly higher levels of PD-1 and PD-L1 gene expression, higher amounts of sTILs and PD-L1+ immune and tumor cells. Hierarchical clustering of all immunological biomarkers revealed three cluster: “Inflamed high” (n = 13, 20%), “Inflamed low” (n = 22, 33.8%), and “Uninflamed” (n = 30, 46.2%). There were no significant survival differences for any of these groups (CSS). However, patients with good performance status (ECOG 0) and low PD-L1 expression showed significantly better CSS compared to those with ECOG0 / PD-L1 high and ECOG1 or ECOG2, respectively (30.3 months vs. 16.33, 12.07 and 15.13 months; p = 0.0047).
Conclusions
Immunological determinants of mUC show comparable distributions and correlations with subtypes of localized curatively treated MIBC patients. Interestingly, data indicate improved CSS after PD-1/PD-L1 treatment in patients with good performance and low PD-L1 expression, which warrants validation in larger cohorts.
Clinical trial identification
DRKS00016925.
Editorial acknowledgement
Legal entity responsible for the study
STRATIFYER Molecular Pathology GmbH.
Funding
Janssen-Cilag GmbH.
Disclosure
R. Wirtz: Leadership role: CEO & CSO, STRATIFYER Molecular Pathology GmbH. All other authors have declared no conflicts of interest.
Resources from the same session
3140 - Phase 2 study of olaparib in previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) or homologous recombination repair deficiency (HRD): LYNK-002
Presenter: David Hyman
Session: Poster Display session 3
Resources:
Abstract
2655 - The K-BASKET trial: A prospective phase II biomarker-driven multiple basket trial in Korean solid cancer patients.
Presenter: Seul Kim
Session: Poster Display session 3
Resources:
Abstract
5938 - Cambridge Liquid biopsy “CALIBRATION” study: Can changes in circulating tumour DNA (ctDNA) predict durable tumour responses in patients with advanced oesophageal cancer receiving MEDI4736?
Presenter: Constanza Linossi
Session: Poster Display session 3
Resources:
Abstract
3799 - Validation of a tumour mutational burden workflow on routine histological samples of colorectal cancer and assessment of a cohort with synchronous hepatic metastases
Presenter: Andrea Mafficini
Session: Poster Display session 3
Resources:
Abstract
4647 - Microsatellite Instability Testing and Lynch Syndrome Screening For Colorectal Cancer Patients Through Tumor Sequencing
Presenter: Li Liu
Session: Poster Display session 3
Resources:
Abstract
3231 - "Liquid Withdarw" technique in CT-guided cutting needle lung biopsy: decreased incidence of complications and increased tissue amount for lung cancer molecular testing.
Presenter: Xue Wang
Session: Poster Display session 3
Resources:
Abstract
3282 - WGS Implementation in standard cancer Diagnostics for Every cancer patient (WIDE)
Presenter: Paul Roepman
Session: Poster Display session 3
Resources:
Abstract
5905 - Known and unknown gene fusion detection capabilities of solid tumor laboratories conducting next generation sequencing in 6 countries
Presenter: Steph Finucane
Session: Poster Display session 3
Resources:
Abstract
4238 - Clinical and Analytical Accuracy of a 523 Gene Panel Next-Generation Sequencing (NGS) Assay on Formalin-Fixed Paraffin-Embedded (FFPE) Solid Tumor Samples
Presenter: Ina Deras
Session: Poster Display session 3
Resources:
Abstract
2493 - Methylation analysis of MLH1 using droplet digital PCR and methylation sensitive restriction enzyme.
Presenter: Celine De Rop
Session: Poster Display session 3
Resources:
Abstract