Cancer Research and Treatment

Original Articles

Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer: Jong Ho Cho, Wei Zhou, Yoon-La Choi, Jong-Mu Sun, Hyejoo Choi, Tae-Eun Kim, Marisa Dolled-Filhart, Kenneth Emancipator, Mary Anne Rutkowski, Jhingook Kim; Cancer Res Treat. 2018;50(1):95-102. Published online March 17, 2017; DOI: https://doi.org/10.4143/crt.2016.591

Purpose
Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC).
Materials and Methods
We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR-mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis.
Results
All patients had ≥ 1 EGFR mutation—54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1–positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1–positive groups (TPS ≥ 1%) compared with the PD-L1–negative group (median, 35 months).
Conclusion
PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR-mutant NSCLC.

Citations

Citations to this article as recorded by

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Yi Dong, Liaqat Khan, Yi Yao
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Hyunjin Kim, Maixian Liu, Chan Hyeok Park, Byung Il Lee, Hyonchol Jang, Yongdoo Choi
Journal of Materials Chemistry B.2024; 12(42): 10877. CrossRef
Influence of PD‐L1 expression on the efficacy of EGFR‐TKIs in EGFR‐mutant non‐small cell lung cancer
Si‐Yu Lei, Hai‐Yan Xu, Hong‐Shuai Li, Ya‐Ning Yang, Fei Xu, Jun‐Ling Li, Zhi‐Jie Wang, Pu‐Yuan Xing, Xue‐Zhi Hao, Yan Wang
Thoracic Cancer.2023; 14(24): 2327. CrossRef
Association of PD‐L1 tumor proportion score ≥20% with early resistance to osimertinib in patients with EGFR‐mutated NSCLC
Yusuke Hamakawa, Yoko Agemi, Aya Shiba, Toshiki Ikeda, Yuko Higashi, Masaharu Aga, Kazuhito Miyazaki, Yuri Taniguchi, Yuki Misumi, Yukiko Nakamura, Tsuneo Shimokawa, Yusuke Saigusa, Nobuaki Kobayashi, Hiroaki Okamoto, Takeshi Kaneko
Cancer Medicine.2023; 12(17): 17788. CrossRef
Determining Risk Factors Associated with Depression and Anxiety in Young Lung Cancer Patients: A Novel Optimization Algorithm
Yu-Wei Fang, Chieh-Yu Liu
Medicina.2021; 57(4): 340. CrossRef
Anti-PD1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer with Actionable Oncogenic Driver Mutations
Edouard Dantoing, Nicolas Piton, Mathieu Salaün, Luc Thiberville, Florian Guisier
International Journal of Molecular Sciences.2021; 22(12): 6288. CrossRef
Programmed Death Ligand 1 Expression and Related Markers in Pleuropulmonary Blastoma
Zahra Alipour, Kris Ann P Schultz, Ling Chen, Anne K Harris, Ivan A Gonzalez, John Pfeifer, D Ashley Hill, Mai He, Louis P Dehner
Pediatric and Developmental Pathology.2021; 24(6): 523. CrossRef
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Bo Lan, Yongfang Wang, Jingni Wu, Kai Wang, Pingli Wang
Medicine.2021; 100(34): e27038. CrossRef
The Clinicopathological and Molecular Associations of PD-L1 Expression in Non-small Cell Lung Cancer: Analysis of a Series of 10,005 Cases Tested with the 22C3 Assay
Matthew Evans, Brendan O’Sullivan, Frances Hughes, Tina Mullis, Matthew Smith, Nicola Trim, Philippe Taniere
Pathology & Oncology Research.2020; 26(1): 79. CrossRef
PD-L1 expression and response to pembrolizumab in patients with EGFR-mutant non-small cell lung cancer
Eriko Miyawaki, Haruyasu Murakami, Keita Mori, Nobuaki Mamesaya, Takahisa Kawamura, Haruki Kobayashi, Shota Omori, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Toshiaki Takahashi
Japanese Journal of Clinical Oncology.2020; 50(5): 617. CrossRef
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Mai He, Brooj Abro, Madhurima Kaushal, Ling Chen, Tiffany Chen, Mercia Gondim, Weisi Yan, Julie Neidich, Louis P. Dehner, John D. Pfeifer
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Clinicopathological characteristics of primary lung nuclear protein in testis carcinoma: A single‐institute experience of 10 cases
Yoon Ah Cho, Yoon‐La Choi, Inwoo Hwang, Kyungjong Lee, Jong Ho Cho, Joungho Han
Thoracic Cancer.2020; 11(11): 3205. CrossRef
Impact of EGFR mutation on the clinical efficacy of PD-1 inhibitors in patients with pulmonary adenocarcinoma
Jang Ho Cho, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
Journal of Cancer Research and Clinical Oncology.2019; 145(5): 1341. CrossRef
The canonical TGF-β/Smad signalling pathway is involved in PD-L1-induced primary resistance to EGFR-TKIs in EGFR-mutant non-small-cell lung cancer
Yang Zhang, Yuanyuan Zeng, Ting Liu, Wenwen Du, Jianjie Zhu, Zeyi Liu, Jian-an Huang
Respiratory Research.2019;[Epub] CrossRef
Association with PD-L1 Expression and Clinicopathological Features in 1000 Lung Cancers: A Large Single-Institution Study of Surgically Resected Lung Cancers with a High Prevalence of EGFR Mutation
Lee, Kim, Sung, Lee, Han, Kim, Choi
International Journal of Molecular Sciences.2019; 20(19): 4794. CrossRef
Clinical and Molecular Predictors of PD-L1 Expression in Non–Small-Cell Lung Cancer: Systematic Review and Meta-analysis
Fausto Petrelli, Mariangela Maltese, Gianluca Tomasello, Barbara Conti, Karen Borgonovo, Mary Cabiddu, Mara Ghilardi, Michele Ghidini, Rodolfo Passalacqua, Sandro Barni, Matteo Brighenti
Clinical Lung Cancer.2018; 19(4): 315. CrossRef
Status of programmed death-ligand 1 expression in sarcomas
Hyung Kyu Park, Mingi Kim, Minjung Sung, Seung Eun Lee, Yu Jin Kim, Yoon-La Choi
Journal of Translational Medicine.2018;[Epub] CrossRef
Association between PD-L1 expression and driver gene status in non-small-cell lung cancer: a meta-analysis
Bo Lan, Chengxi Ma, Chengyan Zhang, Shoujie Chai, Pingli Wang, Liren Ding, Kai Wang
Oncotarget.2018; 9(7): 7684. CrossRef
Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma
Byung Soo Lee, Dong Il Park, Da Hye Lee, Jeong Eun Lee, Min-kyung Yeo, Yeon Hee Park, Dae Sik Lim, Wonyoung Choi, Da Hye Lee, Geon Yoo, Han-byul Kim, Dahyun Kang, Jae Young Moon, Sung Soo Jung, Ju Ock Kim, Sang Yeon Cho, Hee Sun Park, Chaeuk Chung
Biochemical and Biophysical Research Communications.2017; 491(2): 493. CrossRef

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A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer: Hyun Jung Lee, Dae-Seog Heo, Joo-Youn Cho, Sae-Won Han, Hye-Jung Chang, Hyeon-Gyu Yi, Tae-Eun Kim, Se-Hoon Lee, Do-Youn Oh, Seock-Ah Im, In-Jin Jang, Yung-Jue Bang; Cancer Res Treat. 2014;46(3):234-242. Published online July 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.3.234

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. Materials and Methods Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m², and the dose of HM30181A was escalated from 30-210 mg/m². Results A total of twenty-four patients were enrolled. Only one patient experienced a doselimiting toxicity—a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m² of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m² and the area under the curve of plasma concentration- time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m². The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m². The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m². Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. Conclusion The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m².

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