Abstract B27: Longitudinal evaluation of PD-L1 expression on circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab
Authors: Ikeda Mio , Koh Yasuhiro , Teraoka Shunsuke , Sato Koichi , Tokudome Nahomi , Hayata Atsushi , Akamatsu Hiroaki , Ozawa Yuichi , Akamatsu Keiichiro , Endo Katsuya , Higuchi Masayuki , Nakanishi Masanori , Ueda Hiroki , Yamamoto Nobuyuki 
Published: June 2020

Abstract
Purpose: Though programmed death receptor-ligand 1 (PD-L1) expression on tumor tissue is a validated predictive biomarker for PD-1 pathway blockade in NSCLC, its longitudinal change during the treatment remains elusive. We have previously reported that PD-L1-positive rate on CTCs at baseline was correlated with response to nivolumab. Here, we conducted a longitudinal investigation of PD-L1 expression on CTCs in NSCLC patients treated with nivolumab and its association with clinical outcome.
Methods: For CTC detection, 3mL of peripheral blood was collected from advanced NSCLC patients treated with nivolumab at baseline and week 4, 8, 12, and 24 or until progressive disease (PD). The samples were enriched using the microcavity array system based on the difference in size. CTCs were defined as DAPI-positive, CK-positive, and CD45-negative cells and evaluated for PD-L1 expression by additional immunostaining.
Results: Forty-five patients were enrolled between January 2016 and January 2018 at Wakayama Medical University. The patient characteristics were as follows: median age 68 years (range, 49-86); male 75%; stage III/IV, 25/75%; adenocarcinoma/ squamous cell carcinoma/other, 68/25/7%; partial response/stable disease/PD/not evaluable, 20/25/45/9%. At baseline, CTCs were evaluated in 44 patients (median, 13; range, 1-104) and PD-L1 positive CTCs were detected in 82% of patients (median 29%; range, 0-100%); at week 4, evaluated in 31 patients (median, 4; range, 0-115) and detected in 58% of patients (median, 13%; range, 0-100%); at week 8, evaluated in 16 patients (median, 11; range, 1-276) and detected in 56% of patients (median, 7%; range, 0-60%); at week 12, evaluated in 13 patients (median, 11; range, 0-449) and detected in 62% of patients (median, 15%; range, 0-88%); and at week 24, evaluated in 11 patients (median, 8; range, 0-35) and detected in 55% of patients (median, 26%; range, 0-92%). Cutoff value of PD-L1-positivity rates in CTCs to segregate durable clinical benefit (DCB) from non-DCB was calculated to be 7% at week 8 according to receiver operating characteristic curve. Progression-free survival was significantly longer in the patients with less than 7% of PD-L1 positivity rates (n = 8) than in those with 7% or more (n = 8) (p &lt; 0.01) at week 8, suggesting the predictive significance of early evaluation of PD-L1 expression on CTCs after nivolumab treatment. It, however, did not translate into the predictive significance in overall survival. The change in CTC count at PD did not significantly differ between PD and last evaluation point before PD compared to that in non-PD patients at each evaluation point, suggesting the change in CTC count may not be predictive of disease progression upon nivolumab treatment.
Conclusion: Longitudinal evaluation of PD-L1-expressing CTCs may have a predictive potential in NSCLC patients treated with nivolumab. Evaluation in a larger cohort is warranted to confirm the results.
Citation Format: Mio Ikeda, Yasuhiro Koh, Shunsuke Teraoka, Koichi Sato, Nahomi Tokudome, Atsushi Hayata, Hiroaki Akamatsu, Yuichi Ozawa, Keiichiro Akamatsu, Katsuya Endo, Masayuki Higuchi, Masanori Nakanishi, Hiroki Ueda, Nobuyuki Yamamoto. Longitudinal evaluation of PD-L1 expression on circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B27.