NIVOREN GETUG-AFU 26 translational study: CD8 infiltration and PD-L1 expression are associated with outcome in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) treated with nivolumab (N)

Background The NIVOREN GETUG-AFU 26 study reported safety and efficacy of N in mccRCC pts in a “real world setting”. A translationnal research program was launched to characterize immune cell populations in and around the tumor by immunohistochemistry (IHC) and correlate them with outcome on N. Methods All pts treated with N in the GETUG AFU 26 NIVOREN trial who consented for translational program and with available archived paraffin-embedded (FFPE) tumor tissue samples were eligible. Tumor were centrally reviewed. Densities of CD3-, CD8- and CD20-cells and tertiary lymphoid structures (TLS) were estimated by IHC. PD-L1 expression was quantified as percentage of positive tumor cells (TC) and immune cells (IC). Results Overall 324 pts were included. Pts had similar baseline characteristics (IMDC Good, Intermediate, Poor in 18%, 60% and 22%, respectively) than overall trial population. Median PFS was 4.5 (2.9-5.2) months and median OS 25.4 (23.6-NE) months. Highest density of CD8 T cells at the invasive margin (IM) was associated with worse PFS (2.3 vs 4.6 months, HR = 3.96 (1.84-8.51), p = 0.0001) and OS (8.6 vs 25.4 months, HR = 2.43 (0.99-5.95), p = 0.0451). PD-L1 expression on TC (³1%) was associated with worse OS (22.7 vs 29.1 months, HR = 1.51 (1.06-2.15), p = 0.0232) but not PFS (3.5 vs 4.6 months, p = 0.5121). PD-L1 expression on IC (³1%) was associated with numerically shorter median OS (24.7 months vs NR, HR = 1.34 (0.95-1.88), p = 0.0955). CD8 densities, either in the T or at the IM were associated with high PD-L1 expression (>1%) by TC or by IC (all p Conclusions We report the largest translational analysis supporting that highest CD8 density at the IM is associated with worse OS and PFS while PD-L1 expression by ³1% TC or IC is associated with worse OS in pts with mccRCC receiving N. Clinical trial identification NCT03013335. Legal entity responsible for the study UNICANCER. Funding Institut National du Cancer, Direction Generale de l’Offre de Soins, Bristol-Myers-Squibb. Disclosure Y. Vano: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Astellas. N. Rioux-Leclercq: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Ipsen. B. Beuselinck: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS. M. Gross-Goupil: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: GSK. S. Negrier: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Eusa Pharma. D. Borchiellini: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Janssen-Cilag; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas; Honoraria (self), Advisory / Consultancy: Sanofi. B. Escudier: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Eusa Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Aveo. L. Albiges: Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: Ipsen; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Novartis. All other authors have declared no conflicts of interest.