Yasuto Yoneshima1, Kayo Ijichi2, Satoshi Anai1, Keiichi Ota1, Kohei Otsubo1, Eiji Iwama1, Kentaro Tanaka1, Yoshinao Oda3, Yoichi Nakanishi4, Isamu Okamoto5. 1. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 2. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 3. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 4. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 5. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. Electronic address: okamotoi@kokyu.med.kyushu-u.ac.jp.
Abstract
OBJECTIVES: Expression of programmed cell death-ligand 1 (PD-L1) has been associated with clinical outcome of programmed cell death-1 (PD-1) pathway blockade in non-small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay, the only companion diagnostic for pembrolizumab therapy, has revealed that ∼30% of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1 expression in NSCLCs with known driver oncogenes has remained unclear, however. MATERIALS AND METHODS: We retrospectively evaluated PD-L1 expression with the 22C3 assay in tumor tissue of 80 lung adenocarcinoma patients including 71 with EGFR mutations and 9 with ALK rearrangements, all of whom were treated with corresponding tyrosine kinase inhibitors (TKIs). RESULTS: Of the 80 tumors analyzed, 26 (32.5%) had a PD-L1 tumor proportion score (TPS) of 1%-49% and 9 (11.3%) had a PD-L1 TPS of ≥50%; 35 (43.8%) thus had a PD-L1 TPS of ≥1%. Of the 71 tumors with EGFR mutations, 23 (32.4%) had a PD-L1 TPS of 1%-49% and 7 (9.9%) had a PD-L1 TPS of ≥50%. A PD-L1 TPS of ≥1% was not associated with any clinical characteristic examined. Progression-free survival on initial TKI treatment was significantly poorer for patients with a PD-L1 TPS of ≥1% than for those with a PD-L1 TPS of <1% (p = .016). CONCLUSIONS: A subset of patients with EGFR mutations or ALK rearrangements had a PD-L1 TPS of ≥50%. Prospective studies are thus warranted to examine the efficacy of PD-1/PD-L1 inhibitors in such patients.
OBJECTIVES: Expression of programmed cell death-ligand 1 (PD-L1) has been associated with clinical outcome of programmed cell death-1 (PD-1) pathway blockade in non-small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay, the only companion diagnostic for pembrolizumab therapy, has revealed that ∼30% of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1 expression in NSCLCs with known driver oncogenes has remained unclear, however. MATERIALS AND METHODS: We retrospectively evaluated PD-L1 expression with the 22C3 assay in tumor tissue of 80 lung adenocarcinomapatients including 71 with EGFR mutations and 9 with ALK rearrangements, all of whom were treated with corresponding tyrosine kinase inhibitors (TKIs). RESULTS: Of the 80 tumors analyzed, 26 (32.5%) had a PD-L1 tumor proportion score (TPS) of 1%-49% and 9 (11.3%) had a PD-L1 TPS of ≥50%; 35 (43.8%) thus had a PD-L1 TPS of ≥1%. Of the 71 tumors with EGFR mutations, 23 (32.4%) had a PD-L1 TPS of 1%-49% and 7 (9.9%) had a PD-L1 TPS of ≥50%. A PD-L1 TPS of ≥1% was not associated with any clinical characteristic examined. Progression-free survival on initial TKI treatment was significantly poorer for patients with a PD-L1 TPS of ≥1% than for those with a PD-L1 TPS of <1% (p = .016). CONCLUSIONS: A subset of patients with EGFR mutations or ALK rearrangements had a PD-L1 TPS of ≥50%. Prospective studies are thus warranted to examine the efficacy of PD-1/PD-L1 inhibitors in such patients.
Authors: Zhenlin Yang; Yue Peng; Wei Guo; Jiachen Xu; Lin Li; He Tian; Renda Li; Lei Liu; Fengwei Tan; Shugeng Gao; Jie He Journal: Thorac Cancer Date: 2021-05-12 Impact factor: 3.500