A retrospective study of low-dose apatinib combined with S-1 in patients with advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20666-e20666
Author(s):  
Tong Zhou ◽  
Xiaoyue Zhou ◽  
Peng Li ◽  
Changling Wu ◽  
Changsong Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Retrospective Study ◽  
Small Cell Lung Cancer ◽  
Low Dose ◽  
Standard Treatment ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e20666 Background: Currently regimen for advanced non-small cell lung cancer (NSCLC) failing from standard treatment is deficient. This retrospective study aimed to assess the efficacy and safety of low-dose apatinib in combination with S-1 therapy in this NSCLC setting. Methods: In this retrospective study, advanced NSCLC patients who failed from standard treatment in Changzhou Cancer Hospital of Soochow University were screened for eligibility. Progression-free survival (PFS) was set as the primary endpoint. Overall response rate (ORR), disease control rate (DCR), Overall survival (OS) and safety profile were considered to be the secondary endpoints. Results: 31 eligible patients were included in this study. The median PFS (mPFS) was 102 days (95% CI: 57-147). 7 patients (23%; 95% CI: 11-38%) achieved an objective response and the DCR was maintained in 23 patients (75%; 95% CI: 58-86%). The median OS (mOS) was 422 days (95% CI: 148-696).Patients with smoking had a tendency for shorter overall survival without significant differences (HR = 4.105, 95% CI: 0.874-19.288, P = 0.074). Treatment-related grade 3 toxicity was observed in five patients (16%) and the common grade 1 or 2 adverse events were fatigue (42%), hypertension (32%), and hand-foot-skin reaction (23%). Conclusions: Combination of low-dose apatinib and S-1 could be effective and tolerable for advanced NSCLC patients failed from standard treatment, but further exploration in larger clinical trials is needed.

scholarly journals Insulin-like growth factor 1 receptor expression in advanced non-small-cell lung cancer and its impact on overall survival

2017 ◽  
Vol 51 (2) ◽  
pp. 195-202 ◽  
Author(s):  
Mojca Humar ◽  
Izidor Kern ◽  
Gregor Vlacic ◽  
Vedran Hadzic ◽  
Tanja Cufer
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Igf1r Expression

Abstract Background The insulin-like growth factor 1 receptor (IGF1R) expression has been addressed as a potential prognostic marker in non-small-cell lung cancer (NSCLC) in various studies; however, the associations between IGF1R expression and prognosis of advanced NSCLC patients is still controversial. The aim of our observational, cohort study was to evaluate the expression of IGF1R in advanced NSCLC and its prognostic role. A subgroup analysis was performed to address the influence of pre-existing type 2 diabetes mellitus (T2DM) status on IGF1R expression and overall survival (OS). Patients and methods IGF1R expression was evaluated in 167 consecutive advanced NSCLC patients (stage IIIB and IV), diagnosed and treated at one university institution, between 2005 and 2010. All patients received at least one line of standard cytotoxic therapy and 18 of them had pre-existing T2DM. IGF1R expression was determined by immunohistochemical (IHC) staining, with score ≥ 1+ considered as positive. Information on baseline characteristics, as well as patients’ follow-up data, were obtained from the hospital registry. Associations of IGF1R expression with clinical characteristics and overall survival were compared. Results IGF1R expression was positive in 79.6% of patients, significantly more often in squamous-cell carcinoma (SCC) compared to non-squamous-cell (NSCC) histology (88.7% vs. 74.3%; P = 0.03). IGF1R positivity did not correlate with T2DM status or with other clinical features (sex, smoking status, performance status). Median OS was similar between IGF1R positive and IGF1R negative group (10.2 vs. 8.5 months, P = 0.168) and between patients with or without T2DM (8.7 vs. 9.8 months, P = 0.575). Neither IGF1R expression nor T2DM were significant predictors of OS. Conclusions IGF1R or T2DM status were not significantly prognostic in described above collective of advanced NSCLC treated with at least one line of chemotherapy. In addition, no association between T2DM status and IGF1R expression was found. Further studies on IGF1R expression and its prognostic as well as therapeutic consequences in a larger collective of advanced NSCLC patients, with or without T2DM, are needed.

Italian multicentric trial comparing chemotherapy with or without low-dose interleukin-2 (IL-2) in advanced non-small cell lung cancer: Results from a phase III randomized study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8019-8019
Author(s):  
M. Ballardini ◽  
L. Ridolfi ◽  
O. Bertetto ◽  
A. Santo ◽  
E. Naglieri ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Low Dose ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Ecog Ps ◽  
Nsclc Patients

8019 Background: Non small cell lung cancer (NSCLC) is associated with an IL-2-dependent cell-mediated immunodeficiency, and lymphocyte count is considered an independent prognostic factor as it seems to correlate with overall survival. A phase III randomized Italian multicentric trial was conducted to evaluate the efficacy of subcutaneous low-dose IL-2 added to standard CT on overall survival (OS) in advanced NSCLC patients. Methods: Histologically/cytologically confirmed stage IIIb or IV non operable NSCLC patients with measurable disease, ECOG PS 0–2, age 18–70 years and adequate bone marrow, renal and liver function were eligible for the study. Randomization was stratified by center, ECOG PS, stage of disease and percentage of weight loss. All patients received gemcitabine (1000mg/m2) on days 1 and 8 + cisplatin (100mg/m2) on day 2 every 21 days for a maximum of 6 cycles (CT arm). In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3–5; 9–11; 15–17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 120 patients per arm. Results: From June 2000 to October 2004, 241 patients were randomized (arm A/B: 127/114). At a median follow up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 logrank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, logrank). Conclusions: The study did not show any relevant difference in clinical outcome by the addition of IL-2 to CT. Safety and subgroup analyses are ongoing to verify the efficacy of IL-2 as a function of clinical and biological characteristics of patients and tumors. Future studies to investigate the role of T-regulators in chemoimmunotherapy strategies, unknown when the study was originally planned, could be conducted. No significant financial relationships to disclose.

scholarly journals Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Wang ◽  
Zhixuan Ren ◽  
Bentong Yu ◽  
Jian Tang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Cancer Genomics ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Introduction Immune checkpoint inhibitors (ICIs) have become a frontier in the field of clinical technology for advanced non-small cell lung cancer (NSCLC). Currently, the predictive biomarker of ICIs mainly including the expression of PD-L1, TMB, TIICs, MMR and MSI-H. However, there are no official biomarkers to guide the treatment of ICIs and to determine the prognosis. Therefore, it is essential to explore a systematic nomogram to predict the prognosis of ICIs treatment in NSCLC Methods In this work, we obtained gene expression and clinical data of NSCLC patients from the TCGA database. Immune-related genes (IRGs) were downloaded from the ImmPort database. The detailed clinical annotation and response data of 240 advanced NSCLC patients who received ICIs treatment were obtained from the cBioPortal for Cancer Genomics. Kaplan–Meier survival analysis was used to perform survival analyses, and selected clinical variables to develop a novel nomogram. The prognostic significance of FGFR4 was validated by another cohort in cBioPortal for Cancer Genomics. Results 3% of the NSCLC patients harbored FGFR4 mutations. The mutation of FGFR4 were confirmed to be associated with PD-L1, and TMB. Patients harbored FGFR4 mutations were found to have a better prolonged progression-free survival (PFS) to ICIs treatment (FGFR4: P = 0.0209). Here, we built and verified a novel nomogram to predict the prognosis of ICIs treatment for NSCLC patients. Conclusion Our results showed that FGFR4 could serve as novel biomarkers to predict the prognosis of ICIs treatment of advanced NSCLC. Our systematic prognostic nomogram showed a great potential to predict the prognosis of ICIs for advanced NSCLC patients.

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

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.

scholarly journals Pretreatment plasma d-dimer levels as an independent prognostic factor for overall survival among patients with advanced non-small-cell lung cancer

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096266
Author(s):  
Qianfei Liu ◽  
Jianbo He ◽  
Ruiling Ning ◽  
Liping Tan ◽  
Aiping Zeng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Multivariate Analyses ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kaplan Meier ◽  
D Dimer

Objective To evaluate the prognostic accuracy of d-dimer levels for advanced non-small-cell lung cancer (NSCLC). Methods This retrospective cohort study included 651 patients initially diagnosed with advanced NSCLC. Patients with d-dimer levels ≥0.5 mg/L were included in the high d-dimer group, whereas patients with lower levels were included in the normal group. Cumulative survival was estimated using Kaplan–Meier curves and compared using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. Results The median plasma d-dimer level in the study cohort was 0.61 ± 0.49 mg/L. d-dimer levels were elevated in 60.98% of patients, and 80.1% of such patients had adenocarcinoma. Univariate and multivariate analyses identified d-dimer content as an independent factor for the prognosis of NSCLC (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.19–1.98). Kaplan–Meier analysis revealed that high plasma d-dimer levels were associated with shorter overall survival (HR = 1.48, 95% CI = 1.19–1.84). In addition, the receipt of <2 lines of treatment was associated with a higher risk of death than the receipt of >2 lines. Conclusion The present results imply that pretreatment plasma d-dimer levels could represent a prognostic factor for advanced NSCLC.

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

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.

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

2019 ◽  
Vol 17 (1) ◽  
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.

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

2020 ◽  
Vol 15 (1) ◽  
pp. 11-19 ◽  
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.

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