P57.02 Integration of Systemic / Tumor PD-L1 as a Predictive Biomarker of Clinical Outcome in Advanced NSCLC Patients Treated With Anti-PD-(L)1 Agents

2021 ◽  
Vol 16 (10) ◽  
pp. S1136-S1137
Author(s):  
G. Anguera Palacios ◽  
C. Zamora Atenza ◽  
M. Riudavets Melià ◽  
L. Alserawan De Lamo ◽  
I. Sullivan ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Advanced Nsclc ◽  
Predictive Biomarker ◽  
Nsclc Patients

scholarly journals Blood Tumor Mutational Burden as a Predictive Biomarker in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuhui Ma ◽  
Quan Li ◽  
Yaxi Du ◽  
Jingjing Cai ◽  
Wanlin Chen ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Nsclc Patients ◽  
The Impact ◽  
The Relationship

This study was designed to investigate the impact of blood tumor mutational burden (bTMB) on advanced NSCLC in Southwest China. The relationship between the tTMB estimated by next-generation sequencing (NGS) and clinical outcome was retrospectively analyzed in tissue specimens from 21 patients with advanced NSCLC. Furthermore, the relationship between the bTMB estimated by NGS and clinical outcome was retrospectively assessed in blood specimens from 70 patients with advanced NSCLC. Finally, 13 advanced NSCLC patients were used to evaluate the utility of bTMB assessed by NGS in differentiating patients who would benefit from immunotherapy. In the tTMB group, tTMB ≥ 10 mutations/Mb was related to inferior progression-free survival (PFS) (hazard ratio [HR], 0.30; 95% CI, 0.08-1.17; log-rank P = 0.03) and overall survival (OS) (HR, 0.30; 95% CI, 0.08-1.16; log-rank P = 0.03). In the bTMB group, bTMB ≥ 6 mutations/Mb was associated with inferior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank P < 0.01) and OS (HR, 0.31; 95% CI, 0.14-0.7; log-rank P < 0.01). In the immunotherapy section, bTMB ≥ 6 mutations/Mb was related to superior PFS (HR, 0.32; 95% CI, 0.14-1.35; log-rank P < 0.01) and objective response rates (ORRs) (bTMB < 6: 14.2%; 95% CI, 0.03-1.19; bTMB ≥ 6: 83.3%; 95% CI, 0.91-37.08; P = 0.02). These findings suggest that bTMB is a validated predictive biomarker for determining the clinical outcome of advanced NSCLC patients and may serve as a feasible predictor of the clinical benefit of immunotherapies (anti-PD-1 antibody) in the advanced NSCLC population in Yunnan Province.

scholarly journals Peripheral Blood Autoantibodies Against to Tumor-Associated Antigen Predict Clinical Outcome to Immune Checkpoint Inhibitor-Based Treatment in Advanced Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Zhou ◽  
Jing Zhao ◽  
Qingzhu Jia ◽  
Qian Chu ◽  
Fei Zhou ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Peripheral Blood ◽  
Immune Checkpoint Inhibitor ◽  
Advanced Nsclc ◽  
Validation Cohort ◽  
Checkpoint Inhibitor ◽  
Predictive Biomarker ◽  
Line Treatment ◽  
Tumor Associated Antigen ◽  
Nsclc Patients

BackgroundPeripheral blood biomarkers to immunotherapy have attracted more and more attentions owing to noninvasive nature. This study was designed to identify a panel of tumor associated autoantibodies (TAAbs) in plasma to predict the clinical outcome of ICIs-based treatment in advanced NSCLC patients and correlation between TAAbs and checkpoint inhibitor pneumonitis (CIP) would also be investigated.Materials and MethodsBaseline plasma was collected from patients with advanced NSCLC before receiving ICIs-based treatment. ELISA was used to detect concentration of autoantibodies. Clinical efficacy was evaluated according to RECIST v1.1.ResultsWe have identified a panel of five-TAAbs to predict responses of ICIs-based treatment in a discovery cohort (n = 37), and confirmed its predictive value in a validation cohort (n = 129). In the validation cohort, the positivity of this 5-TAAbs panel was significantly associated with better response (ORR: 44.4% vs. 13.6%, P < 0.001) and longer PFS (7.6 vs. 3.3m, P < 0.001). This significant association was remained in subgroup of patients treated with combination therapy (ORR: 43.8% vs. 13.7%, P = 0.004,PFS: 6.7 vs. 3.7m, P = 0 .017). Furthermore, this 5-TAAs panel worked better in patients who received subsequent-line treatment (ORR: 42.4% vs. 7.7%, P = 0.001, PFS: 6.2 vs. 3.0m, P = 0.004) than those received first-line treatment (ORR: 46.7% vs. 35.7%, P = 0.345, PFS: NR vs. 10.48m, P = 0.146). In addition, the CIP incidence in patients with 5-TAAbs positive was significantly higher comparing to negative patients (20.4% vs. 5.9%, P = 0.015).ConclusionOur 5-TAAbs panel is a potential predictive biomarker for responses and toxicities to ICIs-based treatment in patients with advanced NSCLC.

scholarly journals Circulating Tumor Cell PD-L1 Expression as Biomarker for Therapeutic Efficacy of Immune Checkpoint Inhibition in NSCLC

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 809 ◽  
Author(s):  
Kloten ◽  
Lampignano ◽  
Krahn ◽  
Schlange
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Advanced Nsclc ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Immune Checkpoint Blockade ◽  
Tissue Samples ◽  
Programmed Death ◽  
Nsclc Patients

Over the last decade, the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced non-small cell lung cancer (NSCLC) patients. PD-L1 tumor expression, along with tumor mutational burden, is currently being explored as a predictive biomarker for responses to immune checkpoint inhibitors (ICIs). However, lung cancer patients may have insufficient tumor tissue samples and the high bleeding risk often prevents additional biopsies and, as a consequence, immunohistological evaluation of PD-L1 expression. In addition, PD-L1 shows a dynamic expression profile and can be influenced by intratumoral heterogeneity as well as the immune cell infiltrate in the tumor and its microenvironment, influencing the response rate to PD-1/PD-L1 axis ICIs. Therefore, to identify subgroups of patients with advanced NSCLC that will most likely benefit from ICI therapies, molecular characterization of PD-L1 expression in circulating tumor cells (CTCs) might be supportive. In this review, we highlight the use of CTCs as a complementary diagnostic tool for PD-L1 expression analysis in advanced NSCLC patients. In addition, we examine technical issues of PD-L1 measurement in tissue as well as in CTCs.

RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced NSCLC patients treated with cisplatin-based chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8097-8097
Author(s):  
C. Zhou ◽  
S. Zhou ◽  
L. Zhang
Keyword(s):  
Clinical Outcome ◽  
Mrna Expression ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Stage Iiib ◽  
Expression Levels ◽  
Platinum Based Chemotherapy ◽  
Brca1 Mrna ◽  
Nsclc Patients ◽  
Mrna Expression Levels

8097 Background: Platinum-based chemotherapy is the standard treatment for advanced NSCLC patients. RRM1 and BRCA1 are important regulators of chemosensitivity of NSCLC. Methods: Stage IIIb/IV NSCLC patients were given cisplatin-based chemotherapy based upon expression levels of RRM1 and BRCA1 mRNA in the tumor. Expression levels of the two genes were determined by real-time PCR and cut-off points were reported in our previous study. The patients with low expression of RRM1 were treated with gemcitabine/cisplatin up to 4 cycles. The others were treated with vinorelbine or paclitaxel plus cisplatin up to 4 cycles. After the chemotherapy, the patients were followed every 6 weeks up to disease progression and then every 3 months up to death. Results: 90 chemonaive, stage IIIB/IV, PS 0–1 NSCLC patients were enrolled. Age 60 (40–78) yrs old, male/female: 73/27%; adenocarcinoma/squamous/adeno-squamous/undefined NSCLC: 49/33/11/7%;,stage IIIb/IV: 13/87%. Overall response rate was 41.1%, stable disease 42.2%, progressive disease 16.7%. Disease was not progressive in 33 patients. Median TTP was 5 months. Response rate and TTP were better in those with low RRM1 expression ( Table ). Toxicity of the chemotherapy was acceptable. Overall survival will be reported in the conference. Conclusions: RRM1 and BRCA1 mRNA expression levels in non-small cell lung cancer are associated with clinical outcome to cisplatin-based chemotherapy. Prospective studies are ongoing to evaluate the role of the two genes in tailoring chemotherapy in our center. [Table: see text] No significant financial relationships to disclose.

Association of plasma EGFR T790M ctDNA status with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 8080-8080
Author(s):  
Di Zheng ◽  
Xin Ye ◽  
Meizhuo Zhang ◽  
Yun Sun ◽  
Jiying Wang ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Advanced Nsclc ◽  
Tki Resistance ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr T790m

scholarly journals Precision Medicine for NSCLC in the Era of Immunotherapy: New Biomarkers to Select the Most Suitable Treatment or the Most Suitable Patient

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1125 ◽  
Author(s):  
Giovanni Rossi ◽  
Alessandro Russo ◽  
Marco Tagliamento ◽  
Alessandro Tuzi ◽  
Olga Nigro ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Small Cell Lung ◽  
Specific Patient ◽  
Suitable Treatment ◽  
New Biomarkers ◽  
Nsclc Patients

In recent years, the evolution of treatments has made it possible to significantly improve the outcomes of patients with non-small cell lung cancer (NSCLC). In particular, while molecular targeted therapies are effective in specific patient sub-groups, immune checkpoint inhibitors (ICIs) have greatly influenced the outcomes of a large proportion of NSCLC patients. While nivolumab activity was initially assessed irrespective of predictive biomarkers, subsequent pivotal studies involving other PD-1/PD-L1 inhibitors in pre-treated advanced NSCLC (atezolizumab within the OAK study and pembrolizumab in the Keynote 010 study) reported the first correlations between clinical outcomes and PD-L1 expression. However, PD-L1 could not be sufficient on its own to select patients who may benefit from immunotherapy. Many studies have tried to discover more precise markers that are derived from tumor tissue or from peripheral blood. This review aims to analyze any characteristics of the immunogram that could be used as a predictive biomarker for response to ICIs. Furthermore, we describe the most important genetic alteration that might predict the activity of immunotherapy.

Soluble BTN2A1 as a potential predictive biomarker of immune checkpoint inhibitor efficacy in advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9561-9561
Author(s):  
Philippe Rochigneux ◽  
Anne Sophie Chretien ◽  
Delphine Rossille ◽  
Brice Chanez ◽  
Emilien Billon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Advanced Nsclc ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Immune Checkpoints ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Plasmatic Concentration

9561 Background: Medical treatment of lung cancer has irreversibly changed since the development of immune checkpoint inhibitors (ICI). However, immune biomarkers of efficacy are still lacking. Preliminary data in leukemia and pancreatic cancer showed that soluble immune checkpoints are associated with a reduced overall survival (OS). This led us to explore the prognostic and predictive value of soluble immune checkpoints in non-small cell lung cancer (NSCLC) patients treated with chemotherapy or ICI. Methods: We analyzed 90 advanced NSCLC patients. The pilot cohort (Rennes University Hospital, France), included 48 patients treated with platinum doublets (n = 33) or ICI (n = 15) (LOC/11-16 protocol). The confirmation cohort (Paoli-Calmettes Institute) included 42 patients treated with ICI (nivolumab or pembrolizumab) in a longitudinal prospective setting (Immunosup trial, NCT03595813). In both cohorts, enzyme-linked immunosorbent assays (ELISA) were performed in baseline plasma samples for soluble forms of PD-1, PD-L1, global BTN3, BTLA, BTN3-A1 and BTN2A1. Soluble ICI levels were linked to clinical data using Kaplan-Meier, log-rank and Cox proportional-hazards models. Cut-points were determined using maxstat package for survival, R software R 3.6.2. Results: Five soluble immune checkpoints correlated and clustered together in unsupervised analysis (PD-1, PD-L1, global BTN3, BTLA, BTN3-A1), but were not associated with ICI efficacy. In patients treated with ICI, in the pilot and confirmation cohort, a high baseline plasmatic concentration of soluble BTN2A1 was significantly associated with an improved OS (confirmation cohort with a BTN2A1 cut-point of 3.55 ng/ml: HR = 0.30, 95%CI = 0.12-0.74, p = 0.0057, median OS in BTN2A1low = 7.6 months and median OS in BTN2A1hi = 19.5 months). On the contrary, in patients treated with chemotherapy, soluble BTN2A1 concentration was not associated with overall survival. Conclusions: In advanced NSCLC patients, a high baseline plasmatic concentration of soluble BTN2A1 was correlated with improved outcomes for ICI, but not for chemotherapy, suggesting that baseline soluble BTN2A1 level is a potential predictive biomarker of ICI efficacy. Additional studies are ongoing to confirm this finding.

Leukocytes with bound platelets as a predictive biomarker for immune-related adverse events (irAEs) in advanced non-small cell lung cancer (NSCLC) patients (pts) receiving anti-PD-(L)1 agents.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15047-e15047
Author(s):  
Mariona Riudavets ◽  
Carlos Zamora ◽  
Ivana Sullivan ◽  
Leticia Alserawan ◽  
Andrés Barba ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Predictive Biomarker ◽  
Lower Percentage ◽  
Test Results ◽  
High Group ◽  
Chi Square ◽  
Healthy Donors ◽  
Chi Square Test ◽  
Grade 3 ◽  
Nsclc Patients

e15047 Background: Anti-PD-(L)1 blocking agents can induce irAEs, compromising treatment continuation and patient safety. Since complexes of leukocyte-platelet have been shown to play a role in inflammation by reducing cytokine production, we hypothesize that the percentage of these complexes could be used as a predictor of irAEs in pts receiving anti-PD-(L)1 agents. Methods: From May 2015 to January 2019, 87 advanced NSCLC pts treated with anti-PD-(L)1 agents at our institution were prospectively included. Percentages of circulating CD4+T lymphocytes and monocytes with bound platelets (CD4+PLT+ and CD14+PLT+, respectively) were obtained by flow cytometry and compared between NSCLC pts and healthy donors (HD, n = 26). The association of leukocyte-platelet complexes with the presence of irAEs was analyzed. According to CD4+PLT+ and CD14+PLT+ levels, NSCLC pts were grouped as CD4+PLT+ high (n = 29), CD4+PLT+ low (n = 58) and as CD14+PLT+ high (n = 36) and CD14+PLT+ low (n = 51). Frequencies and grade of irAEs were compared between groups using Chi-square test. Results: NSCLC pts showed significant higher percentages of circulating CD4+PLT+ and CD14+PLT+ than HD (9.41±0.54% vs. 6.01±0.45% and 57.44±2.42 vs. 35.43±2.22, respectively; p< 0.001). No significant differences in CD4+PLT+ and CD14+PLT+ were found according to the presence of irAEs. CD4+PLT+ high group presented a higher rate of dermatological irAEs while CD4+PLT+ low group showed higher rate of non-dermatological irAEs (dermatological: 44.85% vs. 8.6%; non-dermatological: 10.3% vs. 39.7%, respectively; p< 0.001). Lower percentage of grade ≥2 irAEs was observed in the CD4+PLT+ high group than in the CD4+PLT+ low group (17.3% vs. 41.4%; p< 0.05). No significant differences in the type of irAEs were observed between CD14+ PLT+ high and low groups. Pts with CD4+PLT+ high and CD14+PLT+ low levels showed the lowest rate of irAEs, presenting only grade ≤1 irAEs (53.8% dermatological, 7.7% dermatological + non-dermatological, 38.5% no-irAEs). In contrast, pts with CD4+PLT+ low and CD14+PLT+ high levels presented higher rate of grade ≥3 irAEs (50% grade 0-1, 20% grade 2, 30% grade ≥3; p< 0.05) and predominantly developed non-dermatological irAEs (45% non-dermatological, 30% dermatological + non-dermatological, 25% no-irAEs; p< 0.01). Conclusions: Combining CD4+ PLT+ and CD14+ PLT+ levels may be used as predictive of development and severity of irAEs in advanced NSCLC pts receiving anti-PD-(L)1 agents.

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