In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 619-619
Abstract:
619 Background: Development of predictive biomarkers would help select patients more likely to respond to nivolumab (nivo) in mccRCC. Here we evaluated biomarkers for nivo using endpoints based on either RECIST 1.1 (ORR and PFS) or irRECIST (irORR and irPFS), which were proposed to more accurately predict benefit of immunotherapy. Methods: We retrospectively analyzed tumor tissues from the Checkmate 010 trial (PMID: 25452452). PD-L1 expression on tumor cells (TC) was studied by IHC. Percentages of CD8 + tumor infiltrating cells (TIC) expressing the immune checkpoints PD1, TIM3 and LAG3 (either alone or in various combination) were determined by immunofluorescence (IF) and their predictive value assessed by the presence of a dose response relationship (DRR) with PFS or irPFS. The candidate biomarkers were then correlated with clinical outcomes using optimized cutoffs. Results: As previously shown, TC PD-L1 expression was not associated with PFS or ORR. In contrast, pts with TC PD-L1 ≥1% had longer median irPFS and higher irORR (Table). None of the TIC phenotypes determined by IF displayed a DRR with PFS. Conversely, we found that % of CD8 + TIC that are PD1 + TIM3 - LAG3 - (% CD8 + PD1 + TIM3 - LAG3 - TIC) was correlated with irPFS (HR = 0.58, p = 0.007). At the optimized cutoff (36%), pts with high % CD8 + PD1 + TIM3 - LAG3 - TIC had longer median irPFS and higher irORR (Table). Notably, combination of TC PD-L1 expression with % CD8 + PD1 + TIM3 - LAG3 - TIC identified 3 groups of pts for which irPFS and irORR were significantly different (Table). Conclusions: Our results suggest that, in mccRCC, tumor-immune biomarkers for nivo response show improved association with clinical endpoints defined by irRECIST relative to RECIST. The increased predictive value of TC PD-L1 combined with immune checkpoints expression on CD8 + TIC seen in this cohort requires independent validation. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2018.36.6_suppl.619
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2018
detail.hit.zdb_id:
2005181-5
