scholarly journals Prediction of veristrat test in first-line therapy of pemetrexed based regimen for advanced lung adenocarcinoma patients

2020 ◽  
Author(s):  
Bo Jia ◽  
Zhi Dong ◽  
Di Wu ◽  
Jun Zhao ◽  
Meina Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Progression Free Survival ◽  
Intrinsic Resistance ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Bevacizumab Treatment ◽  
Nsclc Patients ◽  
The Relationship ◽  
Poor Efficacy

Abstract Background: Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcome on pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aim to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods: This study retrospectively analyzed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results: Plasma samples from these patients were analyzed using VS and classified as Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacuzumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression free survival (PFS) (Unreached vs. 4.2 months; P＜0.001) than VS-P patients. Besides, partial response (PR) rate was higher in VS-G than that in VS-P group (46.7% vs 25.0%, P=0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G than that in VS-P group no matter for patients received chemotherapy alone or chemotherapy plus bevacizumab.Conclusions: Our study indicates that VS could be considered as a novel and valid method to predicit efficacy of pemetrexed based therapy and identify a subset of advanced lung adenocarcinoma patients who have intrinsic resistance to pemetrexed based regimen.

scholarly journals Prediction of the VeriStrat test in first-line therapy of pemetrexed-based regimens for advanced lung adenocarcinoma patients

2020 ◽  
Author(s):  
Bo Jia ◽  
Zhi Dong ◽  
Di Wu ◽  
Jun Zhao ◽  
Meina Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Progression Free Survival ◽  
Intrinsic Resistance ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Bevacizumab Treatment ◽  
Nsclc Patients ◽  
The Relationship ◽  
Poor Efficacy

Abstract Background：Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods：This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results：Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P<0.001) than VS-P patients. In addition, the partial response (PR) rate was higher in the VS-G group than that in the VS-P group (46.7% vs 25.0%, P=0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G group than that in the VS-P group regardless of whether patients received chemotherapy alone or chemotherapy plus bevacizumab. Conclusions：Our study indicated that VS might be considered as a novel and valid method to predict the efficacy of pemetrexed-based therapy and identify a subset of advanced lung adenocarcinoma patients who had intrinsic resistance to pemetrexed based regimens. However, larger sample studies are still needed to further confirm this result.

scholarly journals Prediction of the VeriStrat test in first-line therapy of pemetrexed-based regimens for advanced lung adenocarcinoma patients

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Bo Jia ◽  
Zhi Dong ◽  
Di Wu ◽  
Jun Zhao ◽  
Meina Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Progression Free Survival ◽  
Intrinsic Resistance ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Bevacizumab Treatment ◽  
Nsclc Patients ◽  
The Relationship ◽  
Poor Efficacy

Abstract Background Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P < 0.001) than VS-P patients. In addition, the partial response (PR) rate was higher in the VS-G group than that in the VS-P group (46.7% vs. 25.0%, P = 0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G group than that in the VS-P group regardless of whether patients received chemotherapy alone or chemotherapy plus bevacizumab. Conclusions Our study indicated that VS might be considered as a novel and valid method to predict the efficacy of pemetrexed-based therapy and identify a subset of advanced lung adenocarcinoma patients who had intrinsic resistance to pemetrexed based regimens. However, larger sample studies are still needed to further confirm this result.

scholarly journals Prediction of Veristrat Test in First-Line Therapy of Pemetrexed Based Regimen for Advanced Lung Adenocarcinoma Patients

2020 ◽  
Author(s):  
Bo Jia ◽  
Zhi Dong ◽  
Di Wu ◽  
Jun Zhao ◽  
Meina Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Small Cell Lung ◽  
Intrinsic Resistance ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Bevacizumab Treatment ◽  
Nsclc Patients ◽  
The Relationship ◽  
Poor Efficacy

Abstract Background：Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcome on pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aim to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods：This study retrospectively analyzed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results：Plasma samples from these patients were analyzed using VS and classified as Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platnum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacuzumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median PFS (Unreached vs. 4.2 months; P＜0.001) than VS-P patients. Besides, partial response (PR) rate was higher in VS-G than that in VS-P group (46.7% vs 25.0%, P=0.212). Subgroup analysis showed that PFS was also significantly longer in the VS-G than that in VS-P group no matter for patients received chemotherapy alone or chemotherapy plus bevacizumab.Conclusions：Our study indicates that VS could be considered as a novel and valid method to predicit efficacy of pemetrexed based therapy and identify a subset of advanced lung adenocarcinoma patients who have intrinsic resistance to pemetrexed based regimen.

scholarly journals Efficacy of First-Third generation EGFR inhibitor combined with chemotherapy as first-line treatment for advanced lung adenocarcinoma in a real-world setting

2021 ◽  
Author(s):  
Ming-Wei Chen Ming-Wei Chen ◽  
An-Tai He . ◽  
Yi Pei .
Keyword(s):  
Lung Adenocarcinoma ◽  
Survival Time ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Combination Group ◽  
First Line ◽  
Free Survival ◽  
Mean Survival Time ◽  
First Line Therapy ◽  
To Receive

Abstract BackgroundTo explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head-to-head study was performed to compare chemotherapy and gefitinib-erlotinip, osimertinib treatment in combination or with either agent alone as first-line therapy, in terms of efficacy and safety.MethodsA total of 200 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib-erlotinip combined with pemetrexed and carboplatin group, gefitinib-erlotinip osimertinib combined with pemetrexed and carboplatin group, pemetrexed plus carboplatin alone group, or gefitinib-erlotinip alone group, osimertinib alone group.ResultsThe progression-free survival (PFS) of patients in the gefitinib-erlotinip combination group Mean Survival Time PFS 22.00 month,95%CI[16.29,27.70] and osimertinib gefitinib-erlotinip combination group Mean Survival Time PFS 40.00 month,95%CI[28.12,51.87]was longer than that of patients in the chemotherapy alone group PFS10,81 months, 95% CI,[ 8.99–12.64],gefitinib-erlotinip alone group PFS14.00 month.95%CI[11.98-20.01], osimertinib alone group PFS 26.66 month 95%CI[24.77-29.22].The gefitinib-erlotinip osimertinib combinational resulted in longer overall survival (OS) than chemotherapy alone (HR = 0.46, p = 0.016) or gefitinib-erlotinip alone (HR = 0.36, p = 0.01). osimertinib alone (HR = 0.26, p = 0.01).ConclusionsOur finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib-erlotinip and pemetrexed plus carboplatin combined with gefitinib-erlotinip osimertinib group could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.

scholarly journals Effectiveness of Afatinib and Gefitinib in Non-Small Cell Lung Cancer (NSCLC) Epidermal Growth Factor Receptor (EGFR) Mutations in Indonesia: Observational Studies with Retrospectives

2019 ◽  
Vol 10 (4) ◽  
pp. 3516-3522
Author(s):  
Seftika Sari ◽  
Tri Murti Andayani ◽  
Dwi Endarti ◽  
Kartika Widayati
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Medical Records ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Effectiveness data can describe the results or performance of an intervention (treatment) in daily clinical practice and also provide recommendations to policymakers regarding the need or not of health technology to be implemented into the health care system. Research related to the effectiveness of afatinib and gefitinib is still minimal, especially in Indonesia. This study aims to provide an overview of the effectiveness of afatinib and gefitinib in daily clinical practice (the real world) as first-line therapy. This research is an observational study with a retrospective approach that observes the medical records of NSCLC patients who have EGFR mutations in Dr. Sardjito General Hospital Yogyakarta and Dr. Kariadi General Hospital Semarang, Java Island, Indonesia in the period January 2016 - March 2019. The effectiveness seen is the Progress Free Survival and Overall Survival based on the patient's medical records and analyzed using the Kaplan Meier test to see survival. There were 113 patients identified, 27 patients using afatinib and 86 patients using gefitinib. Afatinib had significantly superior progression-free survival (448 days or 14.7 months; 95% CI = 12-17.4 months; p = 0.002) compared to gefitinib (344 days or 11.3 months; 95% CI = 8, 4-14.3 months), however, overall survival of afatinib is no better than gefitinib (472 days or 15.5 months; 95% CI = 13.8-17.2 months vs 653 days or 21.4 months; 95% CI = 18-24.8 months) with a value of p = 0.302. Afatinib has superior progression-free survival compared to gefitinib, but not overall survival as first-line therapy in NSCLC patients with EGFR mutations.

scholarly journals Vasculogenic mimicry, a negative indicator for progression free survival of lung adenocarcinoma irrespective of first line treatment and epithelial growth factor receptor mutation status

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejun He ◽  
Jijun You ◽  
Haibing Ding ◽  
Zhisheng Zhang ◽  
Lin Cui ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Target Therapy ◽  
Vasculogenic Mimicry ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Abstract Background Vascular mimicry (VM) was associated with the prognosis of cancers. The aim of the study was to explore the association between VM and anticancer therapy response in patients with lung adenocarcinoma. Methods This was a single-center retrospective study of patients with lung adenocarcinoma between March 1st, 2013, to April 1st, 2019, at the Second People’s Hospital of Taizhou City. All included patients were divided into the VM and no-VM groups according to whether VM was observed or not in the specimen. Vessels with positive PAS and negative CD34 staining were confirmed as VM. The main outcome was progression-free survival (PFS). Results Sixty-six (50.4%) patients were male. Eighty-one patients received chemotherapy as the first-line treatment, and 50 patients received TKIs. Forty-five (34.4%) patients were confirmed with VM. There was no difference regarding the first-line treatment between the VM and no-VM groups (P = 0.285). The 86 patients without VM had a median PFS of 279 (range, 90–1095) days, and 45 patients with VM had a median PFS of 167 (range, 90–369) days (P < 0.001). T stage (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.10–1.71), N stage (HR = 1.43, 95%CI: 1.09–1.86), M stage (HR = 2.85, 95%CI: 1.76–4.61), differentiation (HR = 1.85, 95%CI: 1.29–2.65), therapy (HR = 0.32, 95%CI: 0.21–0.49), VM (HR = 2.12, 95%CI: 1.33–3.37), and ECOG (HR = 1.41, 95%CI: 1.09–1.84) were independently associated with PFS. Conclusion The benefits of first-line TKIs for NSCLC with EGFR mutation are possibly better than those of platinum-based regimens in patients without VM, but there is no difference in the benefit of chemotherapy or target therapy for VM-positive NSCLC harboring EGFR mutations.

Sequential monitoring of PD-L1 on circulating stromal cells in blood predicts PFS in NSCLC patients undergoing immunotherapy after definitive chemoradiation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8534-8534
Author(s):  
Daniel L Adams ◽  
Alexander Augustyn ◽  
Jianzhong He ◽  
Yawei Qiao ◽  
Ting Xu ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Progression Free Survival ◽  
Free Survival ◽  
Hazard Ratios ◽  
Fda Approval ◽  
Inflammatory State ◽  
Nsclc Patients ◽  
Tumor Biopsies ◽  
Relationship Of ◽  
The Relationship

8534 Background: Cancer Associated Macrophage-Like cells (CAMLs) are circulating stromal cells in the blood of patients (pts) with solid tumors that are phagocytic macrophages that may represent the inflammatory state of the tumor microenvironment. Previously, we demonstrated CAMLs ≥50µm after chemo-radiation therapy (CRT) in NSCLC is associated with worse progression free survival (PFS) and overall survival (OS). We also showed that PDL1 expression in CAMLs is dynamic & can change with CRT, difficult to assess with repeat biopsies, but possible with liquid biopsy. For this study we evaluated whether CAML properties can predict response to CRT with/without immunotherapy (IMT) agents in unresectable NSCLC. Methods: A single blind multi-year prospective study was undertaken to test the relationship of PDL1 expression and ≥50µm CAML size to PFS/OS in NSCLC, pre and post CRT with (n = 96) and without (n = 72) anti-PDL1/PD1 IMT. This included atezolizumab (prospective single arm NCT02525757) n = 39, durvalumab n = 52 or pembrolizumab n = 5 both after 2018 FDA approval. We recruited 168 pts with pathologically confirmed unresectable NSCLC prior to CRT. Blood samples 15 mL were taken at baseline (BL), CRT completion (T1), and ̃1 month after CRT (T2) (with n = 96 or without n = 72 IMT). Blood was filtered by CellSieve filtration and CAMLs quantified for size ( < 49 µm or ≥50 µm) and PDL1 expression to evaluate PFS and OS hazard ratios (HRs) by censored univariate and multivariate analysis at 24 months. Results: CAMLs were found in 90% of all samples, average 5.8 CAMLs/15mL. At BL, ≥50µm CAMLs did not predict PFS in CRT/IMT pts (HR 1.6, p = 0.220) nor CRT alone (HR 1.3, p = 0.593). However, after completion of CRT (T1) ≥50µm CAMLs predicted PFS in CRT/IMT pts (HR 2.7, p = 0.003) and CRT alone (HR 2.5, p = 0.015). In primary tumor biopsies, PDL1 expression > 1% did not predict CRT/IMT response (PFS HR 1.8, p = 0.262 & OS HR 2.3, p = 0.158). At BL, high CAML PDL1 did not predict PFS in CRT/IMT pts (HR 1.4, p = 0.427) nor CRT alone (HR 1.1, p = 0.982). Further, at CRT completion (T1), high CAML PDL1 only trended for better PFS in CRT/IMT pts (HR 1.7, p = 0.137), but not CRT alone (HR 1.1, p = 0.972). At T2, however, pts with continuously high CAML PDL1 had significantly better PFS with IMT (HR 3.2, p = 0.002) vs CRT alone (HR 1.4, p = 0.616). While ≥50µm CAMLs at BL did not predict 24 month progression, ≥50 µm CAMLs after CRT (with or without 1 cycle of anti-PDL1 IMT) was 84% accurate at predicting progression. Further subtyping and analysis is ongoing to evaluate OS and PDL1 in the CAML populations. Conclusions: Our data suggests that in unresectable NSCLC, ≥50 µm CAMLs after completion of CRT is prognostic regardless of IMT use. PDL1 expression in CAMLs also appears to predict for response to consolidated IMT after CRT. Additional studies are needed to validate these findings.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

scholarly journals The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangyun Liu ◽  
Yixuan Zhang ◽  
Miaowen Liu ◽  
Ruoxin Xu ◽  
Fengming Yi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients. Methods We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS). Results We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia. Conclusions The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.

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