scholarly journals Predicting treatment outcomes using 18F-FDG PET biomarkers in patients with non-small-cell lung cancer receiving chemoimmunotherapy

2022 ◽  
Vol 14 ◽  
pp. 175883592110687
Author(s):  
Chang Gon Kim ◽  
Sang Hyun Hwang ◽  
Kyung Hwan Kim ◽  
Hong In Yoon ◽  
Hyo Sup Shim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Scoring System ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Pet Ct ◽  
Laboratory Variables ◽  
First Line Treatment

Background: Predictive markers for treatment response and survival outcome have not been identified in patients with advanced non-small-cell lung cancer (NSCLC) receiving chemoimmunotherapy. We aimed to evaluate whether imaging biomarkers of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and routinely assessed clinico-laboratory values were associated with clinical outcomes in patients with advanced NSCLC receiving pembrolizumab plus platinum-doublet chemotherapy as a first-line treatment. Methods: We retrospectively enrolled 52 patients with advanced NSCLC who underwent baseline 18F-FDG PET/CT before treatment initiation. PET/CT parameters and clinico-laboratory variables, constituting the prognostic immunotherapy scoring system, were collected. Optimal cut-off values for PET/CT parameters were determined using the maximized log-rank test for progression-free survival (PFS). A multivariate prediction model was developed based on Cox models for PFS, and a scoring system was established based on hazard ratios of the predictive factors. Results: During the median follow-up period of 16.7 months (95% confidence interval: 15.7–17.7 months), 43 (82.7%) and 31 (59.6%) patients experienced disease progression and death, respectively. Objective response was observed in 23 (44.2%) patients. In the multivariate analysis, maximum standardized uptake value, metabolic tumour volume2.5, total lesion glycolysis2.5, and bone marrow-to-liver uptake ratio from the PET/CT variables and neutrophil-to-lymphocyte ratio (NLR) from the clinico-laboratory variables were independently associated with PFS. The scoring system based on these independent predictive variables significantly predicted the treatment response, PFS, and overall survival. Conclusion: PET/CT variables and NLR were useful biomarkers for predicting outcomes of patients with NSCLC receiving pembrolizumab and chemotherapy as a first-line treatment, suggesting their potential as effective markers for combined PD-1 blockade and chemotherapy.

scholarly journals Gefitinib in Non Small Cell Lung Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Raffaele Costanzo ◽  
Maria Carmela Piccirillo ◽  
Claudia Sandomenico ◽  
Guido Carillio ◽  
Agnese Montanino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Line Treatment ◽  
Phase 2 ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Treatment

Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) that plays a key role in the biology of non small cell lung cancer (NSCLC). Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

Angiogenesis inhibitor plus erlotinib versus erlotinib alone as first-line for advanced non-small cell lung-cancer harboring EGFR mutation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9569-9569 ◽  
Author(s):  
Thierry Landre ◽  
Gaetan Des Guetz ◽  
Kader Chouahnia ◽  
Boris Duchemann ◽  
Jean F. Morere ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Anti Vegf ◽  
First Line Treatment

9569 Background: Erlotinib is indicated in first line treatment for patients with Non-Small-Cell-Lung cancer (NSCLC) harbouring EGFR mutation. Addition of anti-VEGF in combination with erlotinib in this setting is controversial. Methods: We performed a meta-analysis of randomized trials comparing VEGF inhibitor plus erlotinib with erlotinib alone in first line treatment for advanced NSCLC harbouring EGFR mutation. The outcomes included overall survival (OS), progression-free survival (PFS) objective response rate (ORR), and median duration of response (DOR). A fixed-effect model was used. Results: Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al), and one study evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients (654 with Ex19del and 568 with Leu858Arg);. Most of the patients were women (63%), Asian (85%) and non-smokers (60%), with a median age of 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with improvement of PFS (hazards ratio [HR]: 0.59, 95%CI: 0.51-0.69, p < 0.00001). Improvement in PFS was seen across all subgroups analyzed. Interim analysis of OS (HR: 0.90, 95%CI; 0.68-1.19, p = 0.45) and ORR (odds ratio [OR], 1.19, 0.91-1.55, p = 0.21) were not statistically significant. DOR was statistically longer with combination (p < 0.005). Conclusions: For patients with untreated advanced NSCLC with EGFR mutation, the anti-VEGF combination with erlotinib, compared with erlotinib alone, is associated with significantly improved PFS and DOR, but mature data for OS are needed to confirm the benefit of this strategy.

Randomized Phase III Trial of Paclitaxel/Carboplatin With or Without PF-3512676 (Toll-Like Receptor 9 Agonist) As First-Line Treatment for Advanced Non–Small-Cell Lung Cancer

2011 ◽  
Vol 29 (19) ◽  
pp. 2667-2674 ◽  
Author(s):  
Vera Hirsh ◽  
Luis Paz-Ares ◽  
Michael Boyer ◽  
Rafael Rosell ◽  
Gary Middleton ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Phase Iii ◽  
Line Treatment ◽  
Toll Like Receptor ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Treatment

Purpose This phase III study examined efficacy of the synthetic Toll-like receptor 9–activating oligodeoxynucleotide PF-3512676 in combination with standard paclitaxel/carboplatin chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned (1:1) to receive up to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m2 and carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall survival (OS). Results Baseline demographics were similar across arms (N = 828). Most patients (88%) had stage IV disease. Median OS and median progression-free survival (PFS) were similar (OS: investigational arm, 10.0 months v control arm, 9.8 months; P = .56; PFS: investigational arm, 4.8 months v control arm, 4.7 months; P = .79). Most commonly reported PF-3512676–related adverse events (AEs) were mild-to-moderate local injection site reactions, pyrexia, and flu-like symptoms. In the investigational arm, grades 3 to 4 AEs, including neutropenia, thrombocytopenia, and anemia, were more frequent, and more patients had one or more sepsis-related AEs versus controls (17 v 3). At first interim analysis, the Data Safety Monitoring Committee recommended study discontinuation because of lack of incremental efficacy and more sepsis-related serious AEs in the PF-3512676 arm. Administration of PF-3512676, but not chemotherapy, was halted. Conclusion Addition of PF-3512676 to paclitaxel/carboplatin did not improve OS or PFS versus paclitaxel/carboplatin alone for first-line treatment of patients with advanced NSCLC but did increase toxicity. This regimen cannot be recommended for treating patients with advanced NSCLC.

scholarly journals Effectiveness and Safety of Adding Bevacizumab to Platinum-Based Chemotherapy as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Liu ◽  
Hui-Min Li ◽  
Ran Wang
Keyword(s):  
Lung Cancer ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Subgroup Analyses ◽  
First Line Treatment

Background and Objective: Previous studies have evaluated the efficacy (OS, overall survival; PFS, progression-free survival; ORR, objective response rate) and adverse events of bevacizumab combined with platinum-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer (NSCLC) compared with chemotherapy alone. However, the results were inconsistent.Methods: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library for potentially eligible articles. The outcomes were evaluated in terms of risk ratio (RR) or hazard ratio (HR) and the associated 95% confidence intervals (CIs). Meta-analysis was performed using the Stata 12.0 software, and subgroup analyses were performed based on the treatment and bevacizumab dose.Results: Six randomized controlled trials with 2,465 patients were included in this meta-analysis. The results demonstrated that bevacizumab significantly increased OS (HR = 0.87, 95% CI 0.79–0.96), extended PFS (HR = 0.65, 95% CI 0.54–0.77), and increased ORR (ES = 0.40, 95% CI 0.31–0.48) when added to first-line platinum-based chemotherapy in patients with advanced NSCLC. Subgroup analyses showed that only the higher dose (15 mg/kg) of bevacizumab plus carboplatin–paclitaxel significantly extended the OS and PFS, but both 7.5 mg/kg and 15 mg/kg of bevacizumab improved ORR. However, both 7.5 mg/kg and 15 mg/kg of bevacizumab could only increase PFS and ORR, but not extend OS, when added to cisplatin–gemcitabine. Bevacizumab significantly increased the risk of grade ≥3 events of febrile neutropenia, haemorrhagic events, hypertension, leukopenia, neutropenia, and proteinuria.Conclusion: Bevacizumab significantly increases OS, PFS, and ORR when added to first-line platinum-based chemotherapy in patients with advanced NSCLC, with no new safety signals found. Moreover, bevacizumab (15 mg/kg) plus carboplatin–paclitaxel is a better alternative in increasing OS to carboplatin–paclitaxel and bevacizumab (7.5 mg/kg and 15 mg/kg) plus cisplatin–gemcitabine.

scholarly journals Efficacy of Combination Chemo-Immunotherapy as a First-Line Treatment for Advanced Non-Small-Cell Lung Cancer Patients With HER2 Alterations: A Case Series

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuang Zhao ◽  
Xinghong Xian ◽  
Panwen Tian ◽  
Weimin Li ◽  
Ke Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Nsclc Patients ◽  
First Line Treatment

ObjectiveAlthough the treatment of non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) alterations has been studied for years, the overall response rate (ORR) of these patients is still unsatisfactory, and more therapeutic strategies are needed. Little is known about the combination of chemo- and immunotherapy in HER2-altered lung cancer treatment.Materials and MethodsWe report five cases of advanced NSCLC with HER2 insertion mutation or amplification treated with immunotherapy combined with chemotherapy as the first-line treatment. The HER2 alteration type, duration of treatment and survival were also analyzed.ResultsThe five advanced NSCLC patients, three with HER2 mutations and two with HER2 amplifications, received chemo-immunotherapy as the first-line treatment. The average patient age was 54.6 years. Three patients were females, and two were males. Among all the patients, only one had a smoking history. The immunotherapies used were as follows: two patients were treated with sintilimab, and three patients were treated with pembrolizumab. Only one patient had squamous carcinoma, and she was also the only patient with a complete response (CR). The progression-free survival (PFS) ranged from 2-12 months, with a median PFS of 8.0 months.ConclusionsChemo-immunotherapy may be a promising first-line treatment option for NSCLC patients with HER2 alterations. Further clinical trials are required to confirm this therapeutic option.

scholarly journals Cost-effectiveness analysis of first-line treatment with crizotinib in ROS1-rearranged advanced non-small cell lung cancer (NSCLC) in Canada

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jaclyn M. Beca ◽  
Shaun Walsh ◽  
Kaiwan Raza ◽  
Stacey Hubay ◽  
Andrew Robinson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Advanced Nsclc ◽  
Cost Effective ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
First Line ◽  
Life Years ◽  
First Line Treatment

Abstract Introduction While no direct comparative data exist for crizotinib in ROS1+ non-small cell lung cancer (NSCLC), studies have suggested clinical benefit with this targeted agent. The objective of this study was to assess the cost-effectiveness of crizotinib compared to standard platinum-doublet chemotherapy for first-line treatment of ROS1+ advanced NSCLC. Methods A Markov model was developed with a 10-year time horizon from the perspective of the Canadian publicly-funded health care system. Health states included progression-free survival (PFS), up to two further lines of therapy post-progression, palliation and death. Given a lack of comparative data and small study samples, crizotinib or chemotherapy studies with advanced ROS1+ NSCLC patients were identified and time-to-event data from digitized Kaplan-Meier curves were collected to pool PFS data. Costs of drugs, treatment administration, monitoring, adverse events and palliative care were included in 2018 Canadian dollars, with 1.5% discounting. An incremental cost-effectiveness ratio (ICER) was estimated probabilistically using 5000 simulations. Results In the base-case probabilistic analysis, crizotinib produced additional 0.885 life-years and 0.772 quality-adjusted life-years (QALYs) at an incremental cost of $238,077, producing an ICER of $273,286/QALY gained. No simulations were found to be cost-effective at a willingness-to-pay threshold of $100,000/QALY gained. A scenario analysis assuming efficacy equivalent to the ALK+ NSCLC population showed a slightly more favorable cost-effectiveness profile for crizotinib. Conclusions Available data appear to support superior activity of crizotinib compared to chemotherapy in ROS1+ advanced NSCLC. At the list price, crizotinib was not cost-effective at commonly accepted willingness-to-pay thresholds across a wide range of sensitivity analyses.

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