Investigation of PALB2 Mutation and Correlation With Immunotherapy Biomarker in Chinese Non-Small Cell Lung Cancer Patients

BackgroundPALB2, a gene in the homologous recombination repair (HRR) pathway of the DNA damage response (DDR), is associated with the efficacy of platinum-based chemotherapy, immunotherapy, and PARP inhibitor therapy in several tumors. However, the PALB2 characteristics, its correlation with immunotherapy biomarker, and the prognostic effect of immunotherapy in non-small cell lung cancer (NSCLC) were unknown.MethodsTumor tissue samples from advanced Chinese NSCLC patients were analyzed by next-generation sequencing (NGS) (panel on 381/733-gene). Tumor mutation burden (TMB) is defined as the total number of somatic non-synonymous mutations in the coding region. Microsatellite instability (MSI) was evaluated by NGS of 500 known MSI loci. Programmed Cell Death-Ligand 1 (PD-L1) expression was evaluated using immunohistochemistry (Dako 22C3 or SP263). One independent cohort (Rizvi2018.NSCLC.240.NGS cohort) containing genomic and clinical data from 240 patients with advanced NSCLC and two cohorts (the OAK and POPLAR study cohort) containing genomic and clinical data from 429 patients with advanced NSCLC were used to analyze the prognostic effect of PALB2 on immunotherapy.ResultsGenetic mutation of 5,227 NSCLC patients were analyzed using NGS, of which 162 (3.1%) harbored germline PALB2 mutation (PALB2gmut) and 87 (1.66%) harbored somatic PALB2 mutation (PALB2smut). In NSCLC patients with PALB2gmut and PALB2smut, the most frequently mutated gene was TP53 (65%, 64%). PALB2smut (14.52 Muts/Mb) was associated with higher TMB (p < 0.001) than PALB wild-type (PALB2wt) (6.15 Muts/Mb). However, there was no significant difference in TMB between PALB2gmut (6.45 Muts/Mb) and PALB2wt (6.15 Muts/Mb) (p = 0.64). There was no difference in PD-L1 expression among PALB2gmut, PALB2smut, and PALB2wt. In the Rizvi2018.NSCLC.240.NGS cohort, there was no difference in progression-free survival (PFS) (HR =1.06, p = 0.93) between PALB2 mutation (3.15 months) and PALB2wt (3.17 months). The OAK and POPLAR study cohort of NSCLC patients showed that there was no difference in overall survival (OS) (HR =1.1, p = 0.75) between PALB2 mutation (10.38 months) and PALB2wt (11.07 months).ConclusionsThese findings suggest that PALB2 may not be used as a biomarker for determining prognosis on immunotherapy in NSCLC.

Download Full-text

Circulating mRNA Expression of astrocyte-Elevated Gene-1 Associated with Treatment Response and Survival in Non-Small Cell Lung Cancer Patients Treated with Pemetrexed

10.21203/rs.3.rs-472588/v1 ◽

2021 ◽

Author(s):

You-Lung Chang ◽

Yen-Fu Chen ◽

Ying-Yin Chen ◽

Shih-Chieh Chang ◽

Cheng-Yu Chang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Treatment Response ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Backgrounds: Astrocyte-elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis in non-small cell lung cancer (NSCLC). In this prospective study, we assessed the values of plasma AEG-1 mRNA expression by liquid biopsy associated with tumor response and survival in NSCLC patients treated with pemetrexed. Methods: Patients diagnosed advanced NSCLC were enrolled to be treated with pemetrexed combined platinum as first-line chemotherapy. All patients underwent blood sampling before any cancer treatment (C0) and at first response evaluation after two cycles (C2) treatments. Response to chemotherapy and survival were assessed. Plasma mRNA was extracted from peripheral blood mononuclear cell (PBMC) and quantification of RNA was performed by real-time PCR.Results: A total of 50 patients with advanced NSCLC were included and 13 of 50 patients combined with bevacizumab. In patient groups of SD (n = 13) and PD (n = 10), the plasma mRNA of AEG-1, thymidylate synthase (TS) and CK19 were elevated significantly at C2 compared to patients in treatment response group (PR, n = 27) (PR v.s. SD or PD, AEG-1: 1.22 ± 0.80 v.s. 4.51 ± 15.45, p = 0.043). NSCLC patients had elevated AEG-1 (AEG-1 ≥ 2) after 2-cycle chemotherapy had shorter PFS and OS (high AEG-1 v.s. low AEG-1, median, PFS: 5.5 v.s. 11.9 months, p = 0.021; OS: 25.9 v.s. 40.8 months, p = 0.019, respectively). In Cox regression analysis, increased plasma mRNA expression of AEG-1indicated poor prognosis in survival.Conclusion: Circulating mRNA concentration of AEG-1 could be a predictive and prognostic biomarker in NSCLC patients treated with pemetrexed. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.

Download Full-text

Efficacy and toxicities of combination maintenance therapy in the treatment of advanced non-small-cell lung cancer: an up-to-date meta-analysis

Bioscience Reports ◽

10.1042/bsr20182464 ◽

2019 ◽

Vol 39 (6) ◽

Author(s):

Jianming Hu ◽

Jiawei Hu ◽

Xiaolan Liu ◽

Long Li ◽

Xue Bai

Keyword(s):

Lung Cancer ◽

Maintenance Therapy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Single Agent ◽

Small Cell ◽

Small Cell Lung ◽

Grade 3 ◽

Nsclc Patients

Abstract Background: Single agent maintenance therapy has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) due to its potential survival benefits, but whether combined maintenance therapy would improve the survival of advanced NSCLC remains undetermined. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade 3–4 toxicities. Results: A total of 1950 advanced NSCLC patients received combination maintenance treatment from six trials were included for analysis. The use of doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95%CI: 0.59–0.93, P = 0.010), but not for OS (HR 0.95, 95%CI: 0.85–1.07, P = 0.40) in comparison with single agent maintenance therapy. Similar results were observed in sub-group analysis according to treatment regimens. In addition, there was no significantly risk difference between doublet and single agent maintenance therapy in terms of grade 3/4 hematologic and non-hematologic toxicities. Conclusion: The findings of the present study show that doublet combination maintenance therapy is superior to single agent maintenance therapy in terms of PFS, without increased grade 3–4 toxicities. Future prospective studies are recommended to clearly assess the long-term clinical benefit of doublet maintenance therapy and its impact on health-related quality of life.

Download Full-text

Prognostic significance of peripheral CD8+CD28+ and CD8+CD28− T cells in advanced non-small cell lung cancer patients treated with chemo(radio)therapy

Journal of Translational Medicine ◽

10.1186/s12967-019-2097-7 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 3

Author(s):

Chao Liu ◽

Wang Jing ◽

Ning An ◽

Aijie Li ◽

Weiwei Yan ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

Small Cell Lung Cancer ◽

Natural Killer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Small Cell Lung ◽

Radio Therapy ◽

Nsclc Patients

Abstract Background Noninvasive prognostic biomarkers are needed for advanced non-small cell lung cancer (NSCLC) patients with different histological types to identify cases with poor survival. Here, we investigated the prognostic values of peripheral CD8+CD28+ T cells and CD8+CD28− T cells in advanced NSCLC patients treated with chemo(radio)therapy and the impact of histological type on them. Methods Of 232 registered advanced NSCLC patients, 101 treatment-naïve individuals were eligible and included in our study. Flow cytometry was used to evaluate CD8+CD28+ T cells, CD8+CD28− T cells, CD4+ CD25hi T cells, B cells, natural killer cells, γδT cells, and natural killer T cells in patients’ peripheral blood. Results The median follow-up time was 13.6 months. Fifty-nine (58.4%) patients died by the end of our study. Fifty-three of the 101 advanced NSCLC cases selected for our study were adenocarcinomas (ADs), and 48 were squamous cell carcinomas (SCCs). Multivariate analyses showed that increased levels of CD8+CD28+ T cells independently predicted favorable overall survival (OS) [hazard ratio (HR): 0.51, 95% confidence interval (CI) 0.30–0.89, P = 0.021] and progression-free survival (PFS) (HR: 0.66, 95% CI 0.37–0.93, P = 0.038) in ADs, but the prediction in SCCs was not statistically significant. In contrast, high levels of CD8+CD28− T cells independently predicted unfavorable OS (HR: 1.41, 95% CI 1.17–3.06, P = 0.035) and PFS (HR: 2.01, 95% CI 1.06–3.85, P = 0.029) in SCCs, but the prediction in ADs was not statistically significant. ADs had higher levels of CD4+CD25hi T cells and CD8+CD28− T cells and lower NK cells (all P < 0.05) than SCCs. Conclusions Our findings uncovered the prognostic values of peripheral CD8+CD28+ T cells and CD8+CD28− T cells in advanced NSCLC patients treated with chemo(radio)therapy, which could help to identify patients with poor outcomes and refine treatment strategies.

Download Full-text

The New Immunotherapy Combinations in the Treatment of Advanced Non-Small Cell Lung Cancer: Reality and Perspectives

Current Clinical Pharmacology ◽

10.2174/1574884714666190809124555 ◽

2020 ◽

Vol 15 (1) ◽

pp. 11-19 ◽

Cited By ~ 5

Author(s):

Danilo Rocco ◽

Luigi D. Gravara ◽

Cesare Gridelli

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Significant Shift ◽

Small Cell Lung ◽

Future Directions ◽

Therapeutic Algorithm ◽

Nsclc Patients

Background: In the recent years, immunotherapeutics and specifically immunecheckpoints inhibitors have marked a significant shift in the diagnostic and therapeutic algorithm of Non-Small Cell Lung Cancer (NSCLC), allowing us to use immunotherapeutics alone or combined with chemotherapy for a great subset of patients. However, new interesting approaches are being presently investigated, markedly immunotherapy combinations, that is, the use of two or more immunotherapeutics combined. Methods: In particular, the combination of anti-PD-1 nivolumab and anti-CTLA-4 ipilimumab has already provided groundbreaking positive results in the advanced NSCLC and other combinations are currently under investigation. Results: Therefore, this paper aims to provide a comprehensive state-of-the-art review about immunotherapy combination, along with suggestions about future directions. A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed and ClinicalTrials.gov. Conclusion: Nivolumab plus ipilimumab represent the most promising immunotherapy combination for the treatment of advanced NSCLC patients; safety, tolerability and efficacy of new immunotherapeutics (in monotherapy and in immunotherapy combinations) must be further assessed in future studies.

Download Full-text

Next Generation Sequencing-Based Profiling of Cell Free DNA in Patients with Advanced Non-Small Cell Lung Cancer: Advantages and Pitfalls

Cancers ◽

10.3390/cancers12123804 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3804

Author(s):

Riziero Esposito Abate ◽

Daniela Frezzetti ◽

Monica Rosaria Maiello ◽

Marianna Gallo ◽

Rosa Camerlingo ◽

...

Keyword(s):

Lung Cancer ◽

Next Generation Sequencing ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Small Cell Lung ◽

Free Dna ◽

Nsclc Patients ◽

Generation Sequencing

Lung cancer (LC) is the main cause of death for cancer worldwide and non-small cell lung cancer (NSCLC) represents the most common histology. The discovery of genomic alterations in driver genes that offer the possibility of therapeutic intervention has completely changed the approach to the diagnosis and therapy of advanced NSCLC patients, and tumor molecular profiling has become mandatory for the choice of the most appropriate therapeutic strategy. However, in approximately 30% of NSCLC patients tumor tissue is inadequate for biomarker analysis. The development of highly sensitive next generation sequencing (NGS) technologies for the analysis of circulating cell-free DNA (cfDNA) is emerging as a valuable alternative to assess tumor molecular landscape in case of tissue unavailability. Additionally, cfDNA NGS testing can better recapitulate NSCLC heterogeneity as compared with tissue testing. In this review we describe the main advantages and limits of using NGS-based cfDNA analysis to guide the therapeutic decision-making process in advanced NSCLC patients, to monitor the response to therapy and to identify mechanisms of resistance early. Therefore, we provide evidence that the implementation of cfDNA NGS testing in clinical research and in the clinical practice can significantly improve precision medicine approaches in patients with advanced NSCLC.

Download Full-text

Back to the well: Can patients with advanced non-small cell lung cancer benefit from changing PD-1/PD-L1 inhibitors after progression?

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21194 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21194-e21194

Author(s):

James Newman ◽

Chung-Shien Lee ◽

Kerri McGovern ◽

Nagashree Seetharamu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Small Cell ◽

Small Cell Lung ◽

L1 Data ◽

Nsclc Patients

e21194 Background: Immune checkpoint inhibitors (ICIs) have transformed the standard of care of non-small cell lung cancer (NSCLC) and are capable of inducing a sustained response in a cohort of patients. For those who progress while on ICIs and do not have a targetable mutation, options are typically reduced to chemotherapeutic regimens which have a higher probability of toxicity. In patients with a suboptimal performance status or those who are opposed to receiving chemotherapy and are not eligible or interested in clinical trials, treatments are unfortunately limited. Patients who progress on one ICI do not receive a different ICI as part of standard care in subsequent lines of therapy. Data behind switching ICIs, particularly to those with a different mechanism of action (ie anti-PD-1 followed by anti-PD-L1 or vice versa), are lacking. We evaluated the efficacy of receiving a 2nd ICI in patients with NSCLC. Methods: A single-center, IRB-approved retrospective analysis was conducted of NSCLC patients treated with two different ICIs from March 2015 to July 2020. ICIs were given either in combination with chemotherapy or as monotherapy. Patient and tumoral characteristics, including PD-L1 status (if available) and sequence of ICIs, were captured. A positive PD-L1 was defined as PD-L1 expression > 0%. Progression-free survival (PFS) of each ICI (defined as PFS1 and PFS2) were calculated in months (m) for each patient. Median PFS2 was compared between groups stratified by a cutoff median PFS1 of 3m, sequence of PD-1 and PD-L1 inhibitors, and PD-L1 positive and negative subsets. Mood’s median test was used to compare medians. Results: 26 patients were included in the final analysis. 19/26 patients had a PFS1 > 3m. For this cohort, the median PFS2 was 2.5m (Range: 0.1-36.2) compared to median PFS2 of 1.6m (Range: 0.6-15.9) in patients with PFS1 < 3m (p=0.1847). 15 patients received a PD-1 inhibitor followed by a PD-L1 inhibitor. In this subgroup, the median PFS2 was 1.2m (Range: 0.2-36.2). Alternatively, 7 patients received a PD-L1 inhibitor followed by a PD-1 inhibitor and the median PFS2 in this cohort was 2.3m (Range: 0.1-15.9) (p=0.6471). PD-L1 data was available for 19 patients. 8/19 patients with positive PD-L1 had a median PFS2 of 3.6m (Range: 0.2-13.3) compared to median PFS2 of 1.3m (Range: 0.1-36.2) in patients with negative PD-L1 (p=0.2599). Conclusions: Treatment with a 2nd ICI can potentially provide a modest benefit in patients with advanced NSCLC, and some may even experience a very prolonged response. PFS1, sequence of PD-1/PD-L1 inhibitors, and PD-L1 expression did not show any significant correlation with PFS2. Using a 2nd ICI should be considered for advanced NSCLC patients with diminished performance status or limited treatment options.

Download Full-text

PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10071365 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1365

Author(s):

Margarita Majem ◽

Manuel Cobo ◽

Dolores Isla ◽

Diego Marquez-Medina ◽

Delvys Rodriguez-Abreu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Meta Analysis ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Potential Biomarker ◽

Nsclc Patients

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.

Download Full-text

Are anti-PD1 and anti-PD-L1 alike? The non-small-cell lung cancer paradigm

Oncology Reviews ◽

10.4081/oncol.2020.490 ◽

2020 ◽

Vol 14 (2) ◽

Cited By ~ 1

Author(s):

Giuseppe Luigi Banna ◽

Ornella Cantale ◽

Melissa Bersanelli ◽

Marzia Del Re ◽

Alex Friedlaender ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Response Rate ◽

Indirect Evidence ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Nsclc Patients

Anti-PD1 and anti-PD-L1 agents may have intrinsic and clinically relevant differences in the treatment of non-small cell lung cancer (NSCLC) patients. By reviewing currently available indirect evidence on these agents for NSCLC treatment, highlighting possible inter- and intra-class dissimilarities, anti-PD1 agents showed a higher response rate and a better outcome when combined with chemotherapy for the first-line treatment of patients with squamous and PD-L1 low advanced NSCLC, as compared to anti-PD-L1 agents. Conversely, anti-PD-L1 agents were responsible for less severe adverse events (AEs), particularly, immunerelated AEs. These differences could be explained by their different specific properties. Considering possible differences between anti-PD1 and anti-PD-L1 agents could be clinically relevant for treatment tailoring and inspiring new investigational approaches.

Download Full-text

Association of extended dosing intervals or delays in pembrolizumab-based regimens with survival outcomes in advanced non-small cell lung cancer

10.1101/2020.03.31.20048637 ◽

2020 ◽

Cited By ~ 1

Author(s):

Kartik Sehgal ◽

Anushi Bulumulle ◽

Heather Brody ◽

Ritu R. Gill ◽

Shravanti Macherla ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Significant Proportion ◽

Small Cell ◽

Survival Outcomes ◽

Routine Practice ◽

Small Cell Lung ◽

Nsclc Patients

AbstractBackgroundBesides modeling/simulation-based analysis, no post-approval studies have evaluated optimal administration frequency of pembrolizumab in non-small cell lung cancer (NSCLC).Patients and MethodsWe performed a multicenter retrospective cohort study to evaluate association between survival outcomes and treatment extensions/delays of pembrolizumab-based regimens in advanced NSCLC patients. Those who had received at least four cycles in routine practice were divided into two groups: non-standard (Non-Std: ≥2 cycles at intervals >3weeks ±3days) and standard (Std: all cycles every 3weeks or 1 cycle >3weeks ±3days).ResultsAmong 150 patients, 92 (61%) were eligible for the study (Non-Std:27, Std:65). Reasons for patients with extensions/delays in the Non-Std group included: immune-related adverse events (irAEs,33%), non-irAE-related medical issues (26%), and patient-physician preference (41%). Non-Std group was more likely to have higher PD-L1 tumor proportion score, higher number of treatment cycles and pembrolizumab monotherapy. Univariate and 6-month landmark analyses showed longer median overall survival (OS) and progression-free survival (PFS) in Non-Std group compared to the Std group. After multivariable adjustment for confounding factors, there was no significant difference in OS [HR 1.1 (95%C.I.: 0.3–4.7), p=0.874] or PFS [HR 2.7 (95%C.I.: 0.8–8.8), p=0.094] between the two groups.ConclusionOur study shows that a significant proportion of advanced NSCLC patients receive pembrolizumab-based regimens with extended intervals or delays in routine clinical practice and with similar outcomes to those receiving treatment at label-specified 3-week intervals. Given the durability of benefit seen and the potential for cost reduction and decreased infusion frequency in these patients, this requires validation in prospective trials.MicroAbstractThe most cost-effective administration frequency of pembrolizumab in advanced non-small cell lung cancer (NSCLC) is unknown. We found that a significant proportion of these patients receive pembrolizumab-based regimens with extended intervals or delays in routine practice, with similar outcomes to those on label-specified 3-week interval treatments. Prospective evaluation of alternative dosing strategies is warranted to develop a more fiscally viable and patient-centered model.

Download Full-text

Novel Biomarkers of Dynamic Blood PD-L1 Expression for Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.665133 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiao Yang ◽

Mingjing Chen ◽

Jiaoyang Gu ◽

Kai Niu ◽

Xianlan Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Advanced Nsclc ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Small Cell Lung ◽

Nsclc Patients

BackgroundImmune checkpoint inhibitors (ICIs) have become a high-profile regimen for malignancy recently. However, only a small subpopulation obtains long-term clinical benefit. How to select optimal patients by reasonable biomarkers remains a hot topic.MethodsPaired tissue samples and blood samples from 51 patients with advanced malignancies were collected for correlation analysis. Dynamic changes in blood PD-L1 (bPD-L1) expression, including PD-L1 mRNA, exosomal PD-L1 (exoPD-L1) protein and soluble PD-L1 (sPD-L1), were detected after 2 months of ICIs treatment in advanced non-small-cell lung cancer (NSCLC) patients. The best cutoff values for progression-free survival (PFS) and overall survival (OS) of all three biomarkers were calculated with R software.ResultsIn 51 cases of various malignancies, those with positive tissue PD-L1 (tPD-L1) had significantly higher PD-L1 mRNA than those with negative tPD-L1. In 40 advanced NSCLC patients, those with a fold change of PD-L1 mRNA ≥ 2.04 had better PFS, OS and best objective response (bOR) rate. In addition, a fold change of exoPD-L1 ≥ 1.86 was also found to be associated with better efficacy and OS in a cohort of 21 advanced NSCLC cases. The dynamic change of sPD-L1 was not associated with efficacy and OS. Furthermore, the combination of PD-L1 mRNA and exoPD-L1 could screen better patients for potential benefit from ICIs treatment.ConclusionThere was a positive correlation between bPD-L1 and tPD-L1 expression. Increased expression of PD-L1 mRNA, exoPD-L1, or both in early stage of ICIs treatment could serve as positive biomarkers of efficacy and OS in advanced NSCLC patients.

Download Full-text