scholarly journals Quantification of [18F]afatinib using PET/CT in NSCLC patients, a feasibility study

2020 ◽  
Author(s):  
Eveline Annette van de Stadt ◽  
Maqsood Yaqub ◽  
Adriaan Lammertsma ◽  
Alex Poot ◽  
Patrick Schober ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Information Criterion ◽  
Compartment Model ◽  
Input Function ◽  
Pet Scan ◽  
Time Interval ◽  
Tumour Uptake ◽  
Positron Emission ◽  
Nsclc Patients

Abstract Introduction: Only a subgroup of non-small cell lung cancer (NSCLC) patients benefit from treatment using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as afatinib. Tumour uptake of [18F]afatinib using positron emission tomography (PET) may identify those patients that respond to afatinib therapy. Therefore, the aim of this study was to find the optimal tracer kinetic model for quantification of [18F]afatinib uptake in NSCLC tumours.Methods: [18F]afatinib PET scans were performed in 10 NSCLC patients. The first patient was scanned for the purpose of dosimetry. Subsequent patients underwent a 20 minutes dynamic [15O]H2O PET-scan (370 MBq) followed by a dynamic [18F]afatinib PET-scan (342 ± 24 MBq) of 60 or 90 minutes. Using the Akaike information criterion (AIC), three pharmacokinetic plasma input models were evaluated with both metabolite corrected plasma sampler input and image-derived (IDIF) input functions in combination with discrete blood samples. Correlation analysis of arterial on-line sampling versus IDIF was performed. In addition, perfusion dependency and simplified measures were assessed.Results: Ten patients were included. The injected dose of [18F]afatinib was 341 ± 37 MBq. 15 tumours could be identified in the field of view of the scanner. Based on AIC, tumour kinetics were best described using an irreversible two-tissue compartment model and a metabolite corrected arterial plasma input function (Akaike 37%). Correlation of plasma-based input functions with metabolite-corrected IDIF was very good (r2=0.93). The preferred simplified uptake parameter was the tumour-to-blood ratio over the 60 to 90 minutes time interval (TBR60-90). Tumour uptake of [18F]afatinib was independent of perfusion.Conclusion: The preferred pharmacokinetic model for quantifying [18F]afatinib uptake in NSCLC tumours was the 2T3K_vb model. TBR60-90 showed excellent correlation with this model and is the best candidate simplified method.

scholarly journals Clinical and Molecular Features of Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Tyrosine Kinase Inhibitors (TKIs): Predictive and Prognostic Role of Co-Mutations

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2425
Author(s):  
Paolo Bironzo ◽  
Maria Lucia Reale ◽  
Tessa Sperone ◽  
Fabrizio Tabbò ◽  
Andrea Caglio ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Nsclc Patients

Background: Tyrosine kinase inhibitors (TKIs) show variable efficacy in epidermal growth factor receptor mutation-positive (EGFR+) NSCLC patients, even in patients harbouring the same mutation. Co-alterations may predict different outcomes to TKIs. Methods: We retrospectively analysed all consecutive EGFR+ advanced NSCLC treated with first-line TKIs at our Institutions. NGS with a 22 genes clinical panel was performed on diagnostic specimens. PD-L1 expression was also evaluated. Results: Of the 106 analysed specimens, 59 showed concomitant pathogenic mutations. No differences in OS (mOS 22.8 vs. 29.5 months; p = 0.088), PFS (mPFS 10.9 vs. 11.2 months; p = 0.415) and ORR (55.9% vs. 68.1%; p = 0.202) were observed comparing patients without and with co-alterations. Subgroup analysis by EGFR mutation type and TKIs generation (1st/2nd vs. 3rd) did not show any difference too. No correlations of PD-L1 expression levels by co-mutational status were found. Significant associations with presence of co-alterations and younger age (p = 0.018) and baseline lymph nodes metastases (p = 0.032) were observed. Patients without concomitant alterations had a significant higher risk of bone progression (26.5% vs. 3.3%, p = 0.011). Conclusions: Pathogenic co-alterations does not seem to predict survival nor efficacy of EGFR TKIs in previously untreated advanced NSCLC.

scholarly journals Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fangfang Lv ◽  
Liang Sun ◽  
Qiuping Yang ◽  
Zheng Pan ◽  
Yuhua Zhang
Keyword(s):  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Deletion Polymorphism ◽  
Asian Populations ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. Methods. Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. Results. A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS ( HR = 1.35 , 95% CI: 1.10-1.64, P = 0.003 ) and a tendency toward an unfavorable OS ( HR = 1.22 , 95% CI: 0.99-1.50, P = 0.068 ). Patients with deletion polymorphism had lower ORR ( OR = 0.60 , 95% CI: 0.42-0.85, P = 0.004 ) and DCR ( OR = 0.59 , 95% CI: 0.38-0.90, P = 0.014 ) compared with those without deletion. Conclusion. BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

scholarly journals MET Gene Dysregulation as a Promising Therapeutic Target in Lung Cancer—A Review

2021 ◽  
Vol 11 (12) ◽  
pp. 1370
Author(s):  
Paulina Terlecka ◽  
Paweł Krawczyk ◽  
Anna Grenda ◽  
Janusz Milanowski
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Point Mutations ◽  
Growth Factor Receptor ◽  
Molecular Abnormalities ◽  
Promising Therapeutic Target ◽  
Tumorigenic Activity ◽  
Nsclc Patients

Several molecular abnormalities in the MET gene have been identified, including overexpression, amplification, point mutations, and “skipping mutation” in exon 14. Even though deregulated MET signaling occurs rarely in non-small cell lung cancer (NSCLC), it possesses tumorigenic activity. Since the discovery of the significant role played by MET dysregulations in resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI), many clinical trials have been focused on mechanisms underlying this acquired resistance. Therefore, new therapeutic strategies are being considered in the personalized therapy of NSCLC patients carrying MET abnormalities. First, MET kinase inhibitors (tepotinib and capmatinib) have been shown to be effective in the first and subsequent lines of treatment in NSCLC patients with “skipping mutations” in exon 14 of MET gene. In this article, the authors show the role of MET signaling pathway alterations and describe the results of clinical trials with MET inhibitors in NSCLC patients.

Cost-effectiveness analysis of icotinib versus whole-brain irradiation with or without chemotherapy in EGFR-mutant NSCLC patients with brain metastases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20556-e20556
Author(s):  
Wenqian Li ◽  
Rilan Bai ◽  
Lei Qian ◽  
Naifei Chen ◽  
Yuguang Zhao ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Brain Metastases ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Net Benefit ◽  
Whole Brain Irradiation ◽  
Nsclc Patients ◽  
The Impact

e20556 Background: Non-small-cell lung cancer (NSCLC) patients with brain metastases had a poor prognosis. Despite the traditional methods including radiotherapy and chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) might benefit patients on survival and quality of life. We investigated the cost-effectiveness of icotinib compared with WBI with or without chemotherapy for NSCLC patients with brain metastases. Methods: A markov model was conducted based on the data of BRAIN trial. We compared the economic benefit between icotinib and the combination of WBI and WBI plus chemotherapy group. We considered disease progression as intracranial progression and overall progression separately. Sensitivity analyses were performed to observe the stability of the model. The willingness-to-pay (WTP) was set as 3× per capita gross domestic product ($25929/quality-adjusted life year [QALY]). Results: When considering progression as intracranial progression and overall progression respectively, the incremental cost-effectiveness ratio (ICER) was $930.17/QALY and $842.76/QALY between icotinib and WBI/WBI-chemotherapy. Besides, both of the average cost-effective ratio (average CE) and net benefit showed advantage of icotinib (average CE: $2157.59/QALY for intracranial progression, $2285.16/QALY for overall progression; net benefit: $372153.35 for intracranial progression, $349938.32 for overall progression). One-way sensitivity analyses demonstrated the impact of the utilities of icotinib group. The probabilistic sensitivity analyses showed even at a WTP under $6000/QALY, icotinib could be cost-effective. Conclusions: Icotinib was cost-effective compared with WBI with or without chemotherapy. [Table: see text]

scholarly journals Durable Response to Pazopanib in Recurrent Metastatic Carotid Body Paraganglioma

2020 ◽  
Vol 13 (3) ◽  
pp. 1227-1231
Author(s):  
Bader Alshamsan ◽  
Jean Paul Atallah
Keyword(s):  
Carotid Body ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Metastatic Tumor ◽  
Skeletal Metastases ◽  
Durable Response ◽  
Positron Emission ◽  
Bilateral Lung ◽  
Systemic Symptoms ◽  
The Right

We present the case of a 26-year-old woman living at a high altitude diagnosed initially with nonfamilial and nonsecretory localized carotid body tumor managed with surgery, which developed into a recurrent metastatic tumor treated with cyclophosphamide, vincristine, and dacarbazine. The patient continued to progress and developed a left carotid artery thrombosis and worsening of her systemic symptoms. The patient was re-evaluated, and she decided on no further surgery or systemic therapy. DOTATATE positron emission tomography/computed tomography showed widespread somatostatin-avid disease involving the left carotid bulb mass, bilateral lung nodules, and liver metastases, with the largest in the right hepatic lobe measuring 8 × 7 cm. There were peripancreatic lymph nodes and scattered skeletal metastases. The patient sought a second opinion, on the basis of which she was prescribed pazopanib, to which she showed a dramatic clinical response after 1 month, followed by a durable response for 1 year. Tyrosine kinase inhibitors such as pazopanib are potentially useful in paraganglioma, with further studies needed to understand the role of vascular endothelial growth factor receptor-directed kinase inhibitors in this setting.

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