Prognostic value of the lung immune prognostic index in patients with untreated advanced renal cell carcinoma (aRCC) receiving nivolumab plus ipilimumab (N+I) or sunitinib (SUN) in the CheckMate 214 trial.

Abstract

4538 Background: The Lung Immune Prognostic Index (LIPI), defined by lactate dehydrogenase (LDH) and derived neutrophil to lymphocyte ratio (dNLR), has been shown to correlate with outcomes of immune checkpoint inhibitor therapy in patients (pts) with lung and other cancers, including pts with previously treated aRCC receiving nivolumab in the phase 2 NIVOREN GETUG-AFU 26 trial. We report an analysis of LIPI in pts with previously untreated aRCC receiving N+I or SUN in the randomized phase 3 CheckMate 214 trial with 5 years minimum follow-up. Methods: Data were used from CheckMate 214 comparing N+I (N 3 mg/kg + I 1 mg/kg) vs SUN (50 mg) for untreated aRCC (N = 1096). Pts with available LIPI data were categorized into 3 LIPI groups (good [LG], dNLR ≤ 3 and LDH ≤ upper limit of normal [ULN]); intermediate [LI], dNLR > 3 or LDH > ULN; and poor [LP], dNLR > 3 and LDH > ULN). This analysis focused on the prognostic value of LIPI using overall survival (OS) outcomes. Univariable analyses (UVAs) were conducted to evaluate LIPI groups alongside known risk factors including age, sex, IMDC risk, baseline PD-L1 status, prior nephrectomy, and baseline tumor burden. Variables that were statistically significant in UVAs ( P < 0.1) were included in the full multivariable analyses (MVAs), from which a reduced model was generated. Results: A total of 1085 pts were evaluable for LIPI (N+I, n = 542; SUN, n = 543). Pts were distributed evenly between treatment arms for all 3 LIPI groups, but distribution between LIPI groups was unbalanced, with most pts grouped as LG (Table). OS outcomes were improved with N+I over SUN across all LIPI groups. Moreover, pts in the LG group had better OS outcomes vs pts in the LI or LP groups regardless of treatment, but with more distinct differences between LIPI groups in the SUN arm (Table). Final MVA results showed the LIPI correlated with OS for LI vs LG in the N+I arm and for LI vs LG and LP vs LG in the SUN arm (Table). Conclusions: These results from CheckMate 214 indicate the potential prognostic value of the LIPI in pts with untreated aRCC receiving N+I or SUN. Additional analyses are ongoing to further investigate the prognostic value of LIPI in this pt population and its impact on other clinical outcomes. Clinical trial information: NCT02231749. [Table: see text]