Tomoyuki Naito1, Hibiki Udagawa2, Jun Sato3, Hidehito Horinouchi3, Shuji Murakami3, Yasushi Goto3, Shintaro Kanda3, Yutaka Fujiwara3, Noboru Yamamoto3, Yoshitaka Zenke4, Keisuke Kirita4, Shingo Matsumoto4, Kiyotaka Yoh4, Seiji Niho4, Noriko Motoi5, Yuichiro Ohe3, Genichiro Ishii6, Koichi Goto4. 1. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Japan. 2. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: hudagawa@east.ncc.go.jp. 3. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 4. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 5. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan. 6. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Japan.
Abstract
INTRODUCTION: Programmed death ligand 1 (PD-L1) expression is a predictive biomarker for patient response to nivolumab in nonsquamous NSCLC. However, the number of biopsy samples and tumor cells (TCs) required to assess PD-L1 expression remains unclear. METHODS: A total of 222 biopsy samples from 80 patients with nonsquamous NSCLC treated with nivolumab were collected. Number of TCs and PD-L1 score were compared among the sample containing the largest number of TCs (Max-TC), the sample containing the smallest number of TCs (Min-TC), and the total samples from each patient. The impact of the number of samples and TCs on the prediction of patient response to nivolumab with use of PD-L1 scores was evaluated. RESULTS: There was a mismatch in PD-L1 scores less than 1% and those of at least 1% between Max-TC and the total samples in one patient (1%) and between Max-TC and Min-TC in six patients (8%). The optimal number of TCs to match PD-L1 expression less than 1% versus at least 1% between Max-TC and Min-TC was 100 (sensitivity = 0.676 and 1 - specificity = 0.333). PD-L1 expression of at least 1% in Min-TCs containing at least 100 TCs was associated with longer progression-free survival (median 7.6 versus 1.8 months [p < 0.01]) and overall survival (median not reached versus 9.9 months [p = 0.04]) compared with PD-L1 expression less than 1%. However, there were no differences in progression-free survival (median 3.9 versus 2.3 months [p = 0.37]) or overall survival (median 9.7 versus 7.6 months [p = 0.60]) between PD-L1 expression of at least 1% and PD-L1expression less than 1% in Min-TCs containing fewer than 100 TCs. CONCLUSION: Single biopsy samples containing at least 100 TCs are required to evaluate PD-L1 expression for predicting patient response to nivolumab.
INTRODUCTION:Programmed death ligand 1 (PD-L1) expression is a predictive biomarker for patient response to nivolumab in nonsquamous NSCLC. However, the number of biopsy samples and tumor cells (TCs) required to assess PD-L1 expression remains unclear. METHODS: A total of 222 biopsy samples from 80 patients with nonsquamous NSCLC treated with nivolumab were collected. Number of TCs and PD-L1 score were compared among the sample containing the largest number of TCs (Max-TC), the sample containing the smallest number of TCs (Min-TC), and the total samples from each patient. The impact of the number of samples and TCs on the prediction of patient response to nivolumab with use of PD-L1 scores was evaluated. RESULTS: There was a mismatch in PD-L1 scores less than 1% and those of at least 1% between Max-TC and the total samples in one patient (1%) and between Max-TC and Min-TC in six patients (8%). The optimal number of TCs to match PD-L1 expression less than 1% versus at least 1% between Max-TC and Min-TC was 100 (sensitivity = 0.676 and 1 - specificity = 0.333). PD-L1 expression of at least 1% in Min-TCs containing at least 100 TCs was associated with longer progression-free survival (median 7.6 versus 1.8 months [p < 0.01]) and overall survival (median not reached versus 9.9 months [p = 0.04]) compared with PD-L1 expression less than 1%. However, there were no differences in progression-free survival (median 3.9 versus 2.3 months [p = 0.37]) or overall survival (median 9.7 versus 7.6 months [p = 0.60]) between PD-L1 expression of at least 1% and PD-L1expression less than 1% in Min-TCs containing fewer than 100 TCs. CONCLUSION: Single biopsy samples containing at least 100 TCs are required to evaluate PD-L1 expression for predicting patient response to nivolumab.
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675