5877 - Efficacy of anti-PD(L)1 treatment in patients with metastatic urothelial cancer based on mRNA- and protein- based PD-L1 determination: Results from the multicentric, retrospective FOsMIC trial

Background

Immunotherapy (IO) with antibodies against PD1 or PD-L1 has been approved for 1^st and 2^nd 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 1^st and 2^nd 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.