Safety and efficacy results of a phase IV, open-label, multicenter, safety-monitoring study of icotinib in treating advanced non-small cell lung cancer (NSCLC): ISAFE study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19161-e19161 ◽  
Author(s):  
Fenlai Tan ◽  
Aiqin Gu ◽  
Yiping Zhang ◽  
Shun Chang Jiao ◽  
Chang-li Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Safety Monitoring ◽  
Small Cell ◽  
Small Cell Lung ◽  
Open Label ◽  
Safety And Efficacy ◽  
Monitoring Study ◽  
Nsclc Patients

e19161 Background: The phase III ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS), based on which icotinib was approved by State Food and Drug Administration of China. We conducted a safety-monitoring study to assess the safety and efficacy of icotinib in a broad range of patients with advanced non-small-cell lung cancer (NSCLC) across China. Methods: This study was a single-arm, open-label, multi-center trial in advanced NSCLC patients who were suitable for treatment with oral icotinib 125 mg three times daily. Endpoints included safety, objective response rate (ORR) and disease control rate (DCR), were investigated overall and in subgroups. EGFR mutation analysis was performed retrospectively. Results: Between August, 2011 and August, 2012, 6,087 advanced NSCLC patients were registered with a median age of 63 years (range: 21-95 years), and 5,549 patients were evaluable for safety and tumor response. Baseline characteristics (%) were: male/female 50.8/49.2; non-smoker/ex- or current-smoker/no data 67.2/32.7/0.1; adenocarcinoma/non-adenocarcinoma/other 78.6/15.4/6.0; stage IIIB/IV/other 7.4/90.2/2.4; and 1,571(28.3%) patients were ≥ 70 years of age. The overall incidence of drug-related adverse events (AEs) of any grade was 31.5%, in which the most common drug-related AEs including rash (17.4%) and diarrhea (8.5%), and 3 patients experienced with interstitial lung disease (ILD) associated with icotinib. ORR and DCR were 30.0% and 80.6%, respectively. The safety in the elder patients (age ≥70, n=1,571) were similar to that in the overall population, the incidence of drug-related AEs of any grade was 30.6%, most of which were grade I or II. Among 989 patients who undertook EGFR mutation detection, 738 (74.6%) patients were mutation-positive with an ORR of 49.2% and a DCR of 92.3%. Moreover, in 251 (25.4%) wild type patients, the ORR and DCR were 17.8% and 75.7%, respectively. Conclusions: The data from over 6,000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated efficacy and a favorable toxicity profile in the routine clinical setting.

Effectiveness of osimertinib plus chemotherapy and avastin for untreated EGFR-mutated advanced non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21178-e21178
Author(s):  
Fang Wang ◽  
Hui Liu ◽  
Zhen Zeng ◽  
Shasha Wang ◽  
Haifeng Qin
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Mutated

e21178 Background: Osimertinib is recommended as a novel first-line standard treatment for advanced Non-Small-Cell Lung Cancer (NSCLC) patients with EGFR mutation. However, there are also patients with concurrent mutation or/and metastases have limited benefits. According to the current remission rate, regression depth and PFS data, the main mechanism of the benefit of combined anti-angiogenesis or chemotherapy is to reduce tumor load and heterogeneous reserve to a greater extent, so as to extend the remission time, that is, to delay the occurrence of drug resistance to extend PFS. This prospective study aims to investigate the efficacy and safety of Osimertinib plus chemotherapy and Avastin for Untreated EGFR-Mutated advanced NSCLC. Methods: The study enrolled 22 patients diagnosed with untreated advanced NSCLC and tested with EGFR mutation, who received osimertinib ( 80mg QD) plus pemetrexed (500mg/m2), cisplatin (75mg/m2) and bevacizumab (7.5mg/kg) for 6 cycles, then maintained with osimertinib/pemetrexed/bevacizumab. The primary endpoint was progression free survival (PFS). The secondary endpoint was objective response rate (ORR). Treatment was continued until disease progression and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The toxicity was determined according to CTCAE 4.0. Results: From February, 2018 to July, 2020, 22 patients enrolled. All the patients were evaluated and showed partial response(PR) when make efficacy evaluation at the first time. The target lesions reduction were shown. The average reduction is 48%, ranged from 32% of Pt12 to 71% of Pt11. Up to January, 2021, all the patients are still under the treatment. Especially for Pt7 who has already benefited from the treatment protocol by 35months. The toxicities associated with this protocols were manageable. Only 1 patient was 3/4-grade Anemia, 1 patient was 3/4-grade Diarrhea and 3 patients was 3/4-grade Lymphopenia. Conclusions: Osimertinib in combination with chemotherapy and Bevacizumab. exhibits superior activity and generally manageable toxicities for the naive advanced NSCLC patients with EGFR mutant, especially for the patients with concurrent mutation or/and metastases. It may provide a new and effective therapy strategy for them, but large sample and additional clinical trials are also needed.

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 A Linear Discriminant Analysis Model Based on the Changes of 7 Proteins in Plasma Predicts Response to Anlotinib Therapy in Advanced Non-Small Cell Lung Cancer Patients

2022 ◽  
Vol 11 ◽  
Author(s):  
Fei Xu ◽  
Haiyan Xu ◽  
Zhiyi Wan ◽  
Guangjian Yang ◽  
Lu Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Discriminant Analysis ◽  
Advanced Nsclc ◽  
Predictive Marker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Biomarkers ◽  
Linear Discriminant ◽  
Model Based ◽  
Nsclc Patients

BackgroundAnlotinib is a multi-targeted tyrosine kinase inhibitor mainly targeting angiogenesis signaling. The predictive marker of anlotinib’s efficacy remains elusive. This study was designed to explore the predictive marker of anlotinib in non-small cell lung cancer (NSCLC).MethodsWe prospectively enrolled 52 advanced NSCLC patients who underwent at least one line of targeted therapy or chemotherapy between August 2018 and March 2020. Patients were divided into durable responders (DR) and non-durable responders (NDR) based on the median progression-free survival (PFS, 176 days). The Olink Immuno-Oncology panel (92 proteins) was used to explore the predictive protein biomarkers in plasma samples before treatment (baseline) and on the first treatment evaluation (paired).ResultsAt baseline, the response to anlotinib was not significantly associated with age, gender, smoke history, histology, oligo-metastases, EGFR mutations, and other clinical characteristics. The results of PFS-related protein biomarkers at baseline were all not satisfying. Then we assessed the changes of 92 proteins levels in plasma on the first treatment evaluation. We obtained a Linear discriminant analysis (LDA) model based on 7 proteins, with an accuracy of 100% in the original data and an accuracy of 89.2% in cross validation. The 7 proteins were CD70, MIC-A/B, LAG3, CAIX, PDCD1, MMP12, and PD-L2. Multivariate Cox analysis further showed that the changes of CD70 (HR 25.48; 95% CI, 4.90–132.41, P=0.000) and MIC-A/B (HR 15.04; 95% CI, 3.81–59.36, P=0.000) in plasma were the most significant prognostic factors for PFS.ConclusionWe reported herein a LDA model based on the changes of 7 proteins levels in plasma before and after treatment, which could predict anlotinib responders among advanced NSCLC patients with an accuracy of 100%. Further studies are warranted to verify the prediction performance of the LDA model.

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 Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

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.

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