Abstract A056: Sequential tracking of PD-L1 expression on circulating tumor cells in NSCLC patients treated with nivolumab
Authors: Akamatsu Hiroaki , Koh Yasuhiro , Mori Keita , Kanai Kuninobu , Hayata Atsushi , Tokudome Nahomi , Higuchi Masayuki , Kanbara HIsashige , Akamatsu Keiichiro , Nakanishi Masanori , Ueda Hiroki , Yamamoto Nobuyuki 
Published: August 2018

Abstract
Background: Nivolumab (anti-PD-1 antibody) has become a new standard treatment in pretreated, advanced non-small cell lung cancer (NSCLC). Although strong expression of PD-L1 on tumor tissue has predictive value, significance of its expression on circulating tumor cell (CTC) is unknown and its status can be changed during the treatment. Here, we conducted a serial evaluation of PD-1-expressing CTCs in NSCLC patients treated with nivolumab. Methods: Advanced NSCLC patients who receive nivolumab at Wakayama Medical University Hospital were enrolled in this prospective observational study (registered at UMIN (000024414)). Nivolumab was administered 3 mg/kg biweekly until progressive disease (PD) or unacceptable toxicity. Peripheral whole blood (3 mL) was collected in a EDTA collection tube (BD vacutainer) and processed within 3 hours for CTC evaluation at baseline, week 4, and week 8. CTCs were detected using microcavity array system (Hitachi Chemical Co.). PD-L1 expression was immunohistochemically examined on both tumor tissues and CTCs using anti-PD-L1 antibody, clone 28-8 (Abcam). Results: Thirty-eight patients were registered in this study between January 2016 and September 2016. Clinical characteristics of the patients were as follows: median age 68 (range, 49 to 86); male 73%; stage IV 100%; squamous/non-squamous, 30/65%. Regarding nivolumab treatment, overall response rate (ORR) was 22% (95% confidence interval (CI): 10-38%), and median progression-free survival (PFS) was 62 days (95%CI: 40-235 days). At baseline, CTCs were detected in all patients (median, 15; range, 1-90) and PD-L1-expressing CTCs were detected in 87% of patients. Tumor proportion score (TPS) of PD-L1 expression on CTCs varied from 6% to 100%. Matched tumor tissues were available from 14 patients and 7 showed the PD-L1 TPS ≥ 50%. PD-L1 status on CTCs was not correlated with that on tumor tissues both using proportional score and H score (Spearman’s correlation: r = 0.0007 and 0.08, respectively). On CTCs, patients with PD-L1 ≥ 50 have significantly higher disease control rate than those with below 50% (83.3% versus 36.4%, p&lt;0.01). Similarly, patients with PD-L1 ≥ 50% on CTC was significantly longer PFS compared with those with below 50% (293 days versus 49 days, hazard ratio 2.41 (95% CI: 1.05-5.54), p = 0.03). During nivolumab treatment, number of CTCs was decreased (median number was 10 at 4 weeks and 5 at 8 weeks). Among those with PD-L1 ≥ 50% on CTC at baseline, changes in number and PD-L1 status on CTCs at 4 weeks did not correlate with PFS. Conclusions: Serial monitoring of PD-L1 expression on CTCs during nivolumab treatment was successfully conducted. PD-L1 expression on CTCs at baseline was a strong predictor in efficacy. Predictive significance of PD-L1-positive CTCs should be also evaluated in validation cohort using pembrolizumab.
Citation Format: Hiroaki Akamatsu, Yasuhiro Koh, Keita Mori, Kuninobu Kanai, Atsushi Hayata, Nahomi Tokudome, Masayuki Higuchi, HIsashige Kanbara, Keiichiro Akamatsu, Masanori Nakanishi, Hiroki Ueda, Nobuyuki Yamamoto. Sequential tracking of PD-L1 expression on circulating tumor cells in NSCLC patients treated with nivolumab [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A056.