Xiaoqiao Liu1, Min Gew Choi2, Kyung Kim3, Kyoung-Mee Kim4, Seung Tae Kim5, Se Hoon Park6, Razvan Cristescu7, Senaka Peter8, Jeeyun Lee9. 1. Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: xiao.qiao.liu@merck.com. 2. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. Electronic address: mingew.choi@samsung.com. 3. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. Electronic address: kkyung412@gmail.com. 4. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. Electronic address: kkmkys@skku.edu. 5. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. Electronic address: shty1@skku.edu. 6. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. Electronic address: hematoma@skku.edu. 7. Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: razvan_cristescu@merck.com. 8. Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: senaka_peter@merck.com. 9. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea. Electronic address: jyunlee@skku.edu.
Abstract
BACKGROUND: The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) 22C3 pharmDx assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients, especially in the U.S. The present study investigated the relationship between PD-L1 expression and the clinical features, molecular markers, and molecular subtypes of GC. METHODS: PD-L1 expression was assessed based on combined positive score (CPS) using PD-L1 IHC 22C3 pharmDx in the Asian Cancer Research Group (ACRG) GC cohort (N = 300), which has been previously genomically profiled. PD-L1 positivity was defined as PD-L1 CPS ≥ 1. The association between PD-L1 expression and clinical features, tumor burden, and molecular subtypes (ACRG and The Cancer Genome Atlas [TCGA]) was analyzed. RESULTS: Of the 300 tumors, 178 (59.3 %) had PD-L1 CPS ≥ 1 and 122 (40.7 %) had PD-L1 CPS < 1. PD-L1 CPS ≥ 1 was significantly associated with stage I tumor (P = 0.022), high microsatellite instability (MSI-H) (P < 0.001), Epstein-Barr virus (EBV) positivity (P = 0.008), and positive Helicobacter pylori status (P = 0.001). PD-L1 CPS ≥ 1 was observed in 96/193 (49.7 %) EBV-negative/microsatellite stable (MSS) tumors. In gene expression profiling, PD-L1 CPS was highly correlated with mutational load (P < 0.001) as well as EBV (P < 0.001) and MSI subtypes (P < 0.001); 27/300 (9%) GC patients had a very high PD-L1 (≥ 20) score (MSI-H, n = 10; EBV, n = 6; and non-EBV/MSS, n = 11). OS was longer in patients with PD-L1 CPS ≥ 1 tumors than in those with PD-L1 CPS < 1 tumors (median OS not reached vs. 40 months; P = 0.008; log-rank test). CONCLUSIONS: PD-L1 is expressed in 59.3 % of GC patients and is associated with MSI and EBV positivity. These results provide a basis for identifying GC patients who may benefit from anti-PD-1/PD-L1 therapy.
BACKGROUND: The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) 22C3 pharmDx assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients, especially in the U.S. The present study investigated the relationship between PD-L1 expression and the clinical features, molecular markers, and molecular subtypes of GC. METHODS:PD-L1 expression was assessed based on combined positive score (CPS) using PD-L1 IHC 22C3 pharmDx in the Asian Cancer Research Group (ACRG) GC cohort (N = 300), which has been previously genomically profiled. PD-L1 positivity was defined as PD-L1CPS ≥ 1. The association between PD-L1 expression and clinical features, tumor burden, and molecular subtypes (ACRG and The Cancer Genome Atlas [TCGA]) was analyzed. RESULTS: Of the 300 tumors, 178 (59.3 %) had PD-L1CPS ≥ 1 and 122 (40.7 %) had PD-L1CPS < 1. PD-L1CPS ≥ 1 was significantly associated with stage I tumor (P = 0.022), high microsatellite instability (MSI-H) (P < 0.001), Epstein-Barr virus (EBV) positivity (P = 0.008), and positive Helicobacter pylori status (P = 0.001). PD-L1CPS ≥ 1 was observed in 96/193 (49.7 %) EBV-negative/microsatellite stable (MSS) tumors. In gene expression profiling, PD-L1CPS was highly correlated with mutational load (P < 0.001) as well as EBV (P < 0.001) and MSI subtypes (P < 0.001); 27/300 (9%) GCpatients had a very high PD-L1 (≥ 20) score (MSI-H, n = 10; EBV, n = 6; and non-EBV/MSS, n = 11). OS was longer in patients with PD-L1CPS ≥ 1 tumors than in those with PD-L1CPS < 1 tumors (median OS not reached vs. 40 months; P = 0.008; log-rank test). CONCLUSIONS:PD-L1 is expressed in 59.3 % of GCpatients and is associated with MSI and EBV positivity. These results provide a basis for identifying GCpatients who may benefit from anti-PD-1/PD-L1 therapy.
Authors: Nicole M Myer; Kohei Shitara; Hyun C Chung; Florian Lordick; Ronan J Kelly; Zsolt Szabo; Z Alexander Cao; Stephen Leong; David H Ilson; Wilko Weichert Journal: J Cancer Res Clin Oncol Date: 2022-05-13 Impact factor: 4.322
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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