Abstract 802TiP
Background
Despite the survival advantage observed with nivolumab in pretreated mRCC patients, only a small percentage of them respond to the treatment (20-30%) and experience long-term clinical benefit. There is, therefore, an intense interest and still an unmet need in identifying prognostic and predictive biomarkers to select patients most likely to benefit from immunotherapy. Inflammatory biomarkers from peripheral blood, such as neutrophil-to-lymphocyte ratio (NLR), have shown promising results in retrospective analysis on cancer patients treated with immunotherapy, including mRCC patients.
Trial design
A multicentric retrospective translational study was designed and is ongoing to assess the correlation of immune TME of primary tumor and metastases and peripheral blood inflammatory biomarkers with survival and response outcomes. The analysis of immune TME is conducted on two cohorts of mRCC patients treated with nivolumab as ≥2nd line therapy: responders (PFS ≥12 months) and non-responders (PFS ≤ 3 months). It consists in the immunohistochemical, genomic and transcriptomic analysis of TME including morphological and immunophenotypic evaluation of tumor-infiltrating lymphocytes (TILs) (CD8+,CD4+, FOXP3+ T cells), tumor-associated macrophages polarization (pro-inflammatory M1 and anti-inflammatory M2 macrophages), tissue NLR and lymphocyte-to-monocyte ratio (LMR), population of NK cells and expression of the phosphorilated mTOR effectors S6K1 and 4E-BP. All the assessments of the immune TME are correlated, in terms of response and survival outcomes, with the peripheral blood biomarkers NLR, derived NLR [neutrophil / (white blood cells – neutrophils)], platelet-to-lymphocyte ratio (PLR), LMR and systemic inflammation index (SII; NLR x Platelets) at baseline and during the first four cycles of treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Giuseppe Fornarini.
Funding
IRCCS Ospedale Policlinico San Martino of Genova; Azienda Ospedaliero Universitaria Integrata of Verona.
Disclosure
M. Bersanelli: Research grant/Funding (institution): Seqirus; Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Sanofi. U. Basso: Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen-Cilag; Advisory/Consultancy: MSD; Advisory/Consultancy: Incyte; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Research grant/Funding (self): Ipsen; Travel/Accommodation/Expenses: Astellas Pharma; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Pfizer. G. Fornarini: Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: Astellas; Advisory/Consultancy: Sanofi-Genzyme; Advisory/Consultancy: Roche-Genentech; Advisory/Consultancy: Janssen. All other authors have declared no conflicts of interest.