Authors: Toni K. Choueiri, Amber C Donahue, Brian I. Rini, Thomas Powles, John B. A. G. Haanen, James Larkin, Xinmeng Jasmine Mu, Jie Pu, Despina Thomaidou, Alessandra Di Pietro, Paul B. Robbins, Robert J. Motzer
Published: 2021-06-02
DOI: 10.1200/jco.2021.39.15_suppl.4547
Source: Full article
4547 Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), treatment-naive patients (pts) with aRCC demonstrated prolonged progression-free survival (PFS) and a higher objective response rate with A + Ax vs S. We report the association of blood-based biomarkers with differential responses to treatment. Methods: Biomarkers in pretreatment (pre-tx) and on-treatment (on-tx) blood samples from 886 enrolled pts were correlated with clinical outcomes and molecular profiling data from corresponding tumor samples. Analyses include blood counts of unique populations, T-cell receptor sequencing, circulating cytokines, and serum proteomics by mass spectrometry MALDI-TOF. Results: At baseline, higher pre-tx monocyte counts were associated with shorter PFS in the A + Ax arm (Table). In the S arm, higher pre-tx levels of multiple T-cell–related metrics, including the percent of productively rearranged peripheral T cells, were associated with longer PFS but had no association in the A + Ax arm (Table). Higher pre-tx neutrophil counts were associated with shorter PFS in both arms, but neutrophil-to-lymphocyte ratio (NLR) was only associated with PFS for the S arm (Table). On-therapy biomarkers showed differential post-tx changes in T-cell numbers and clones at C2D1. Tx-specific differences were also seen in non–T-cell populations such as monocytes and neutrophils at multiple time points through C3D1. Serum levels of pre- and on-tx VEGF, CRP, and several interleukins showed differential associations with PFS (eg, higher pre-tx VEGF was associated with shorter PFS in only the S arm) (Table). Specific genomic alterations in tumor tissues were associated with differences in several pre- and on-tx angiokines & cytokines. Conclusions: Response to treatment with first-line A + Ax or S was associated with immune fitness and tx-specific immunomodulation. We identified peripheral biomarkers in pts with aRCC associated with the presence of impactful genomic alterations and differential clinical outcomes. Clinical trial information: NCT02684006. [Table: see text]