PD-L1 Expression in Chinese Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): A Multi-Center Retrospective Observational Study

Yang, Xin; Jiang, Lili; Jin, Yan; Hou, Yuning; Yun, Jing‐Ping; Wu, Chunyan; Sun, Weibo; Fan, Xiangshan; Kuang, Dong; Wang, Weiya; Ni, Jinsong; Mao, Anhua; Tang, Wenmin; Liu, Zhenhua; Wang, Jiali; Xiao, Suijun; Li, Yuan; Lin, Dongmei

doi:10.7150/jca.63003

Cited by 12 publications

(11 citation statements)

References 52 publications

(68 reference statements)

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“…It is essential to realize that the variety of results and different prognostic impact of PD‐L1 in specific subgroups is influenced by the testing method itself (e.g., different antibodies and thresholds) and individual patient‐related characteristics, such as ethnicity or tumor histology. For instance, different proportions of PD‐L1‐positive tumors for distinct histological NSCLC subtypes have been reported 40–43 . In our study, high PD‐L1 TPS score carried both prognostic and predictive value in the ICI treated patients while in the whole cohort, including patients treated in curative settings, only the association between improved OS and CRP level of ≤10 was retained.…”

Section: Discussionmentioning

confidence: 50%

“…For instance, different proportions of PD-L1positive tumors for distinct histological NSCLC subtypes have been reported. [40][41][42][43] In our study, high PD-L1 TPS score carried both prognostic and predictive value in the ICI treated patients while in the whole cohort, including patients treated in curative settings, only the association between improved OS and CRP level of ≤10 was retained.…”

Section: Discussionmentioning

confidence: 63%

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The prognostic and predictive roles of plasma C‐reactive protein and PD‐L1 in non‐small cell lung cancer

et al. 2023

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BackgroundAnti‐PD‐(L)1 agents have revolutionized the treatment paradigms of non‐small cell lung cancer (NSCLC), while predictive biomarkers are limited. It has been previously shown that systemic inflammation, indicated by elevated C‐reactive protein (CRP) level, is associated with a poor prognosis in anti‐PD‐(L)1 treated. The aim of the study was to analyze the prognostic and predictive value of CRP in addition to traditional prognostic and predictive markers and tumor PD‐L1 score.MethodsWe identified all NSCLC patients (n = 329) who had undergone PD‐L1 tumor proportion score (TPS) analysis at Oulu University Hospital 2015–22. CRP levels, treatment history, immune checkpoint inhibitor (ICI) therapy details, and survival were collected. The patients were categorized based on CRP levels (≤10 vs. >10) and PD‐L1 TPS scores (<50 vs. ≥50).ResultsIn the whole cohort (n = 329), CRP level of ≤10 mg/L was associated with improved survival in univariate (HR 0.30, Cl 95% 0.22–0.41) and multivariate analyzes (HR 0.44, CI 95% 0.28–0.68). With ICI treated (n = 70), both CRP of ≤10 and PD‐L1 TPS of ≥50 were associated with improved progression‐free survival (PFS) in univariate (HR 0.51, CI 95% 0.27–0.96; HR 0.54, CI 95% 0.28–1.02) and multivariate (HR 0.48, CI 95% 0.26–0.90; HR 0.50, CI 95% 0.26–0.95) analyzes. The combination (PD‐L1 TPS ≥50 and CRP >10) carried a high negative predictive value with a median PFS of 4.11 months (CI 95% 0.00–9.63), which was similar to patients with low PD‐L1 (4.11 months, CI 95% 2.61–5.60).ConclusionsAdding plasma CRP levels to PD‐L1 TPS significantly increased the predictive value of sole PD‐L1. Furthermore, patients with high CRP beard little benefit from anti‐PD‐(L)1 therapies independent of PD‐L1 score. The study highlights the combined evaluation of plasma CRP and PD‐L1 TPS as a negative predictive marker for ICI therapies.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 63%

The prognostic and predictive roles of plasma C‐reactive protein and PD‐L1 in non‐small cell lung cancer

et al. 2023

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“…A study including 54 EGFR mutation samples identified only 9 samples with PD-L1 expression > 5% accounted for 9.3%. An analysis of PD-L1 expression levels in 871 Chinese NSCLC samples showed that patients with EGFR mutations had slightly lower PD-L1 positivity (43.8% and 49.8%, respectively), while higher PD-L1 expression (TPS ≥ 50%) was significantly lower (14.3% and 27.4%, respectively) compared with EGFR wild-type patients [18]. In addition, comprehensive analysis of PD-L1 and CD8 + TILs in 255 Chinese NSCLC samples showed that the proportion of PD-L1 + and CD8 + TILs double positive in TME was decreased, while the proportion of PD-L1and CD8 -TILs double negative was increased in EGFR mutation group compared with EGFR wild-type group patients (P < 0.01) [19].…”

Section: Discussionmentioning

confidence: 99%

The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer

Liu¹,

Li²,

Zhao³

et al. 2023

J. Cancer

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Background: Immune checkpoint inhibitors (ICIs) are widely used for treating advanced non-small cell lung cancer (NSCLC). However, some studies indicate that patients with genetic mutations do not benefit from immunotherapy. Hence, this study explored the efficacy of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) antibodies in the first-line treatment of advanced NSCLC with driver gene mutations in real-world settings. Methods: We retrospective analyzed patients with advanced NSCLC who treated with first-line anti-PD-1/PD-L1 antibodies at Shandong Provincial Hospital between May 2019 and October 2020. The patient's driver gene mutation status was identified using amplification refractory mutation system PCR (ARMS-PCR). The basic clinical characteristics, objective response rate (ORR), progression free survival (PFS), and other clinical data of patients were collected to evaluate the clinical efficacy and potential prognostic factors of treatment for patients with driver gene mutations. Results: A total of 430 patients' information was counted during this period, finally, 89 patients with NSCLC were enrolled in the study. The main pathological subtype of patients was adenocarcinoma (62.9%). The overall mutation rate was 44.9% (n = 40) and included following mutations: KRAS (n = 20), TP53 (n = 18), EGFR (n = 6), BRAF (n = 3), Her-2 (n = 3), MET (n = 3), ROS1 (n = 1), and NRAS (n = 1). The overall ORR was 44.30% and the disease control rate (DCR) was 82.23%. At the time of follow-up cut-off, the median PFS of all patients was 8.2 month. In NSCLC patients treated with ICI, median PFS was longer in mutation-negative patients than in mutation-positive patients (8.98 vs 7.07 months, P < 0.05). Survival benefit varied across mutational subgroups: KRAS patients could benefit from first-line immunotherapy (10.1 months, P < 0.05), patients with EGFR mutations have poor first-line immunotherapy outcomes, with a median PFS of only 3.0 months (P < 0.01), and patients with other mutation types having no significant difference in response from mutation-negative patients. In most mutation subgroups, immune combination therapy had longer PFS than immune monotherapy, and PD-L1 expression levels were positively correlated with clinical benefit in patients. Conclusion:In the real world, patients with KRAS mutations benefit from first-line immunotherapy, immune-combination modalities are more effective, and immune efficacy is positively correlated with PD-L1 expression; Patients with other driver mutations (BRAF, NRAS, Her2, MET, ROS1) benefit similarly to mutation-negative patients in first-line immunotherapy, and immunotherapy is recommended for first-line therapy; Immunotherapy is worse effective in patients with EGFR mutations, immunotherapy is not recommended in first-line therapy even patients with high PD-L1 expression.

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“…All tissues were fixed with 10% formalin for at least 6 h. All samples were embedded in paraffin and then hematoxylin-eosin staining (HE) and IHC were conducted. All samples were analyzed on an automated stainer with 22C3 (PD-L1 test kits, DAKO/Agilent, USA) (26). At least two pathologists evaluated the slides to determine the scores of PD-L1-positive cells on TC and IC.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

The predictive value of total-body PET/CT in non-small cell lung cancer for the PD-L1 high expression

Jin

et al. 2022

Front. Oncol.

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PurposeTotal-body positron emission tomography/computed tomography (PET/CT) provides faster scanning speed, higher image quality, and lower injected dose. To compensate for the shortcomings of the maximum standard uptake value (SUVmax), we aimed to normalize the values of PET parameters using liver and blood pool SUV (SUR-L and SUR-BP) to predict programmed cell death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients.Materials and methodsA total of 138 (104 adenocarcinoma and 34 squamous cell carcinoma) primary diagnosed NSCLC patients who underwent 18F-FDG-PET/CT imaging were analyzed retrospectively. Immunohistochemistry (IHC) analysis was performed for PD-L1 expression on tumor cells and tumor-infiltrating immune cells with 22C3 antibody. Positive PD-L1 expression was defined as tumor cells no less than 50% or tumor-infiltrating immune cells no less than 10%. The relationships between PD-L1 expression and PET parameters (SUVmax, SUR-L, and SUR-BP) and clinical variables were analyzed. Statistical analysis included χ2 test, receiver operating characteristic (ROC), and binary logistic regression.ResultsThere were 36 patients (26%) expressing PD-L1 positively. Gender, smoking history, Ki-67, and histologic subtype were related factors. SUVmax, SUR-L, and SUR-BP were significantly higher in the positive subset than those in the negative subset. Among them, the area under the curve (AUC) of SUR-L on the ROC curve was the biggest one. In NSCLC patients, the best cutoff value of SUR-L for PD-L1-positive expression was 4.84 (AUC = 0.702, P = 0.000, sensitivity = 83.3%, specificity = 54.9%). Multivariate analysis confirmed that age and SUR-L were correlated factors in adenocarcinoma (ADC) patients.ConclusionSUVmax, SUR-L, and SUR-BP had utility in predicting PD-L1 high expression, and SUR-L was the most reliable parameter. PET/CT can offer reference to screen patients for first-line atezolizumab therapy.

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PD-L1 Expression in Chinese Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): A Multi-Center Retrospective Observational Study

Cited by 12 publications

References 52 publications

The prognostic and predictive roles of plasma C‐reactive protein and PD‐L1 in non‐small cell lung cancer

The prognostic and predictive roles of plasma C‐reactive protein and PD‐L1 in non‐small cell lung cancer

The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer

The predictive value of total-body PET/CT in non-small cell lung cancer for the PD-L1 high expression

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