12P - Prognostic value of PD-L1 expression and neutrophil-to-lymphocyte ratio to neoadjuvant chemo-immunotherapy in muscle-invasive urothelial carcinoma patients from the AURA trial

Background

Immune checkpoint inhibitors (ICI) recently appeared as a promising therapy for early muscle-invasive urothelial carcinoma (MIUC). Despite encouraging response rates, a significant proportion of patients (pts) still dies from lethal relapse. Moreover, validated biomarkers to ICI are lacking. Here, we evaluated PD-L1 expression and neutrophil-to-lymphocyte ratio (NLR) as predictive biomarkers for MIUC pts in the AURA trial.

Methods

AURA is a prospective phase II trial (NCT03674424) evaluating neoadjuvant avelumab (A) alone or in combination with different chemotherapies according to cisplatin eligibility. Baseline PD-L1 expression (IHC, 22C3 Dako) was scored using the combined positive score (CPS). Pre-treatment NLR, absolute neutrophils to lymphocytes ratio, was categorized as low < 3 or high ≥ 3. Associations of biomarkers with pathological responses, event-free survival (EFS) and overall survival (OS) were evaluated using Fisher’s exact test, Kaplan-Meier and Cox regression methods.

Results

Low NLR showed a significant correlation (p<0.05) with pathological complete response (pCR), downstaging (

Conclusions

Low pre-treatment NLR, witnessing low level of systemic inflammation, was significantly associated with response to neoadjuvant chemo-immunotherapy as well as with longer survival, suggesting that NLR could be used as a predictive biomarker for MIUC treatment tailoring, if further validated. In contrast, baseline PD-L1 expression was not correlated with better outcomes.

Editorial acknowledgement

Clinical trial identification

NCT03674424.

Legal entity responsible for the study

Jules Bordet Institute.

Funding

Merck KGaA.

Disclosure

J. Blanc: Financial Interests, Personal, Other, Travel support: Merck, Ipsen, AstraZeneca; Financial Interests, Institutional, Advisory Board: Merck. N. Martinez Chanza: Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Personal, Other, Travel support: Ipsen. A. Carnot: Financial Interests, Personal, Advisory Board: MSD Oncology, Janssen Oncology; Financial Interests, Personal, Invited Speaker: Astellas Pharma. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck, Pfizer, Ipsen, Bayer, Janssen Cilag, Astellas, Novartis, Amgen, Gilead; Financial Interests, Personal, Invited Speaker: AstraZeneca. C. Sotiriou: Financial Interests, Institutional, Advisory Board: Astellas, Vertex, Seattle Genetics, Amgen, INC, Merck & Co; Financial Interests, Personal, Advisory Board: Cepheid, Puma; Financial Interests, Personal, Invited Speaker: Eisai, Prime Oncology, Teva; Financial Interests, Institutional, Other, Travel: Roche; Financial Interests, Institutional, Other, Internal speaker: Genentech; Financial Interests, Personal, Other, Regional speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Personal, Advisory Board, Stock options: Signatur Biosciences. All other authors have declared no conflicts of interest.