Barcelona, Spain ( NIVOREN GETUG AFU 26 is a French multicenter, prospective, phase 2 study that reported safety and efficacy of nivolumab in metastatic clear cell renal cell carcinoma (mccRCC) in a “real world setting.” Results, presented at the GU ASCO 2019 meeting, were notable for a response rate of 21% with a median progression-free survival of 3.7 months and overall survival of 24.5 months after a median follow-up of 23.8 months. In this abstract, the investigators report results of a translational study evaluating whether CD8 infiltration and PD-L1 expression are associated with outcomes in patients with mccRCC treated with nivolumab.

All patients treated with nivolumab who consented for the translational program and with available archived paraffin-embedded tumor tissue samples were eligible. This resulted in a study population of 324 patients from 720 patients in the overall NIVOREN GETUG-AFU 26 study. Tumors were centrally reviewed. Densities of CD3-, CD8- and CD20-cells and tertiary lymphoid structures were estimated by IHC. PD-L1 expression was quantified as the percentage of positive tumor cells (TC) and immune cells (IC).

The majority of tumors had low/mild density of CD8 tumor infiltrating lymphocytes (TILs) at the core of the tumor (54.7%) and at the invasive margin (65.7%). The majority of tumor cells (75.2%) were PD-L1 negative, while, in contrast, the majority of immune cells (59.1%) were PD-L1 positive. Higher infiltration by CD8 TILS in the tumor core is associated with higher expression of PD-L1 in the tumor core and invasive margin.

The investigators then correlated CD8 TIL density and PD-L1 expression with outcomes. CD8 TIL density at the tumor core was not significantly associated with PFS or OS, however, high density of CD8 TILs at the invasive margin was associated with both poorer PFS (HR 2.43, p = 0.04) and OS (HR = 3.96, p = 0.0001). PD-L1 positivity in tumor cells was predictive of increased OS (HR 1.51, p = 0.02), but not PFS (HR 1.10, p = 0.5). The trend towards OS positivity was similar in patients with PD-L1 positivity in the immune cells but did not reach significance (HR 1.34, p = 0.09).

The authors concluded that based on the results, they do not support using these biomarkers on archived tumor samples to guide treatment decisions in mccRCC. Efforts to characterize LAG-3 and TIM-3, as well as mRNA signatures as predictive biomarkers for immunotherapy in mccRCC in the NIVOREN GETUG-AFU 26 cohort, are ongoing.

Presented by: Yann Vano, MD, PhD, Medical Oncologist, Assistance Publique – Hôpitaux de Paris, Paris, France

Written by: Jacob Berchuck, MD, Medical Oncology Fellow at the Dana-Farber Cancer Institute (Twitter: @jberchuck) at the 2019 European Society for Medical Oncology annual meeting, ESMO 2019 #ESMO19, 27 Sept – 1 Oct 2019 in Barcelona, Spain