The quantification of epidermal growth factor receptor (EGFR) in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7597-7597
Author(s):  
C. Camps ◽  
R. Sirera ◽  
M. Muñoz-Navarro ◽  
G. Lopez-Vivanco ◽  
G. Alonso ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Complete Response ◽  
Binding Domain ◽  
Response To Therapy ◽  
First Line Therapy ◽  
Lower Egfr ◽  
Epidermal Growth ◽  
Nsclc Patients

7597 Background: EGFR has an extracellular ligand-binding domain that can be proteolitically cleaved from the cell surface and can be accurately quantified in blood by ELISA. We have investigated the usefulness of plasma EGFR measurements as prognostic marker in advanced NSCLC. Methods: The cohort consisted in 329 patients (p) with advanced NSCLC that received first-line therapy with cisplatin and docetaxel. The concentration levels of the EGFR extracellular binding domain were determined by a sandwich quantitative ELISA in the baseline, before therapy. Results: Median age was 61, range [39–80], 84% males, 100% caucasian, 68% stage IIIB and 32% IV and 99% PS 0–1. The histological subtypes were: 31% squamous cell carcinoma, 49% adenocarcinoma, 15% large cell, and 5% undifferentiated. 181 p achieved complete response (CR), partial response (PR) or stable disease (SD) and 109 p progressive disease (PD). Median patient's plasma levels of EGFR were 32.4 ng/ml. There were not differences in p according to histology, site of metastasis and ECOG. There were differences in response to therapy; CR+PR+SD p presented median EGFR of 31.97 ng/ml [13.2–48.6] vs 30 ng/ml [16.9–46.8] in the PD group (p=0.024). Dividing the cohort in two sets according to EGFR median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with EGFR<32.4 ng/ml had a median TTP of 3.9 months (m) [3.3–4.6] while for EGFR>32.4 ng/ml was 4.7 m [4.0–5.4], (p=0.024). OS when EGFR<32.4 ng/ml was 6.9 m [5.9–7.8] and for EGFR>32.4 ng/ml was 9.1 m [8.2–10.1], (p=0.038). Conclusions: Patients with PD presented significantly lower levels of serum EGFR than those patients with CR+PR+SD. There is a relationship among lower EGFR concentration in serum with a worst prognosis in advanced NSCLC p in terms of TTP and OS. No significant financial relationships to disclose.

The quantification of the catalytic subunit of telomerase in plasma is a prognostic factor in advanced non-small cell lung cancer (NSCLC) patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7052-7052
Author(s):  
R. Sirera ◽  
C. Camps ◽  
L. Llobat ◽  
A. Berrocal ◽  
R. M. Bremnes ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Catalytic Subunit ◽  
Stage Iiib ◽  
Circulating Dna ◽  
Nsclc Patients

7052 Background: Qualitative and quantitative analysis of circulating DNA in blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the free amount in plasma of the catalytic subunit of telomerase (hTERT) and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the serum using commercial adsorption columns. The amount of free hTERT in plasma was quantified by using RT-PCR. Results: Median age was 61 years [35–82] and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Median hTERT value was 4856 ng/ml; for patients in IIIB was 4847 ng/ml [263–964826] and 4886 ng/ml [67–4373520] in stage IV (p = 0.75). There was not association between hTERT values and response to therapy, 20588 ng/ml [122–317251] in the CR+PR group vs 50204 ng/ml [67–4373520] in the SD+PD group (p = 0.09). hTERT values were not related with the localization of the metastasis. Dividing the cohort in two sets according to hTERT median we found two significantly different groups in terms of Overall Survival (OS) and Time To Progression (TTP). Patients with hTERT <4856 ng/ml had a median TTP of 5.3 months (m) [4.4–6.1] while for hTERT >4856 ng/ml was 4.1 m [3.5–4.6], (p = 0.0009). OS when hTERT <4856 ng/ml was 10.1m [4.9–11.3] and for hTERT >4856 ng/ml was 8.4 m [7.2–9.5], (p = 0.01). In the multivariate analysis, hTERT was an independent predictive variable for TTP (HR 1.39, CI 95% 1.1–1.7, p = 0.002) and OS (HR 1.27, CI 95% 1.1–1.6, p = 0.04). Conclusions: In advanced NSCLC patients, the quantification of free circulating hTERT in plasma is an affordable and valuable prognostic marker. High plasma hTERT levels are a poor prognostic indicator for TTP and OS. No significant financial relationships to disclose.

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 Current Approaches in NSCLC Targeting K-RAS and EGFR

2019 ◽  
Vol 20 (22) ◽  
pp. 5701 ◽  
Author(s):  
Veronica Aran ◽  
Jasminka Omerovic
Keyword(s):  
Treatment Options ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Response To Therapy ◽  
Small Cell Lung ◽  
Ras Mutations ◽  
Tk Inhibitors ◽  
Epidermal Growth ◽  
Nsclc Patients ◽  
Viral Oncogene Homolog

The research and treatment of non-small cell lung cancer (NSCLC) have achieved some important advances in recent years. Nonetheless, the overall survival rates for NSCLC remain low, indicating the importance to effectively develop new therapies and improve current approaches. The understanding of the function of different biomarkers involved in NSCLC progression, survival and response to therapy are important for the development of early detection tools and treatment options. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (K-RAS) are two of the main significant biomarkers for the management of NSCLC. Mutations in these genes were associated with development and response to therapies. For example, the use of small molecule tyrosine kinase (TK) inhibitors and immunotherapy has led to benefits in some, but not all patients with altered EGFR. In contrast, there is still no effective approved drug to act upon patients harbouring K-RAS mutations. In addition, K-RAS mutations have been associated with lack of activity of TK inhibitors. However, promising approaches aimed to inhibit mutant K-RAS are currently under study. Therefore, this review will discuss these approaches and also EGFR therapies, and hopefully, it will draw attention to the need of continued research in the field in order to improve the outcomes in NSCLC patients.

Analysis of nerve growth factor (NGF) blood levels in patients with advanced non-small cell lung cancer patients (NSCLC): Its correlation with clinical outcome

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17025-17025
Author(s):  
A. Blasco ◽  
R. Sirera ◽  
C. Camps ◽  
V. Giner ◽  
L. Llobat ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Advanced Nsclc ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Blood Levels ◽  
Dependent Manner ◽  
Lung Cancer Patients ◽  
Response Site

17025 Background: Platinum compounds and taxanes have severe side effects in a dose and time-dependent manner, especially neurotoxicity. NGF plays an important role in growth and differentiation of neuronal components. Our goal was to study NGF levels in plasma and correlate it with patient’s clinico-pathologic characteristics. Methods: The study was performed with 451 patients with advanced NSCLC, stages IIIB-IV and treated with cisplatin and docetaxel. Peripheral blood was collected before therapy. NGF were assessed by commercial ELISA (detection limit, 5 pg/ml). Plasma from 32 age and gender-matched controls was used. Results: 91% of males, mean age 61 y [35–82]. 86 patients in ECOG PS 0–1 and 14 PS2. 71% in stage IV and 29% in IIIB. The histological subtypes were 38% squamous cell, 37% adenocarcinoma, 5% anaplasic large cell and 20% undifferentiated. 77.5% of the metastasis was out of the lung. Patients received a median of 6 cycles of chemotherapy [1–7]. 4% presented complete response (CR), 38% partial response (PR), 25% stable disease (SD) and 30% progressive disease (PD). Patient’s median plasma levels of NGF did not differ significantly from controls: 44 pg/ml [6–176] vs 31 pg/ml [14–144] respectively. There were not differences according to histology, site of metastasis and ECOG; however we could observe significant differences with stage: 25 pg/ml [10–70] in stage IIIB vs 47 pg/ml [6–176] in stage IV (p = 0.008). We could not observe any differences in response to therapy: CR+PR patients presented median NGF of 35 pg/ml [6–92] vs 39 pg/ml [10–165] in the SD+PD group. Splitting the cohort according to NGF median we found two significantly different groups in terms of Overall Survival (OS): patients with NGF <44 pg/ml had a median OS of 10.9 months (m) [7.9–13.9] vs 7.3 m [3–11.5] for patients with NGF >44 pg/ml (p = 0.03). In the multivariate analysis, NGF levels was not predictor for time to progression (TTP) and OS. Conclusions: NGF plasma levels did not differ in patients and controls. In our cohort with advanced NSCLC we have not found any relationship between NGF levels with histology, response, site of metastasis and TTP. By contrast NGF levels are higher in those patients in stage IV and in those presenting poorer OS. No significant financial relationships to disclose.

Ca-15.3 antigen as predictor of response to EGFR inhibitors in patients with bronchiolo-alveolar carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18151-18151
Author(s):  
A. Bearz ◽  
R. Talamini ◽  
E. Vaccher ◽  
M. Spina ◽  
C. Simonelli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Marker ◽  
Growth Factor Receptor ◽  
Female Gender ◽  
Complete Response ◽  
Serum Levels ◽  
Egfr Inhibitors ◽  
First Line Therapy ◽  
Close Relationship ◽  
Epidermal Growth

18151 Background: Bronchiolo-alveolar carcinoma (BAC) is a subtype of non-small cell lung cancer (NSCLC). Incidence of pure BAC ranges between 2% and 5% of NSCLC although a BAC histotype may be present in up to 20%. There is no established treatment for BAC, although promising results have been achieved from the use of inhibitors of the Epidermal Growth Factor Receptor (EGFR). It has been demonstrated that there is a very close relationship between responsiveness to EGFR inhibitors Erlotinib and Gefitinib and some factors, including female gender; adenocarcinoma histotype, with BAC features; Asian origin; and never having smoked. No tumor marker has been validated in the diagnosis and follow-up of lung cancer. Ca 15–3 antigen serum levels are reported to be pathologically abnormal in adenocarcinoma of the lung, although it does not seem to be related to the EGFR pathway. We studied this tumor marker in relation with the treatment with EGFR inhibitors in patients affected by BAC. Methods: We collected data from 16 caucasian, female and never smoker pts with BAC. All pts received EGFR inhibitors as first-line therapy. In compliance with the EAP, dosage of Gefitinib and Erlotinib was 250 mg/day and 150 mg/day, respectively. Results: One (6%) pt had a complete response and 6 (38%) showed a partial response to EGFR inhibitors, 1 (6%) pt remained stable for 4 months, while 8 (50%) pts progressed. All 7 pts with normal Ca 15–3 levels before treatment with EGFR inhibitors’ achieved a partial or complete response, but the 8 pts with abnormal Ca 15–3 levels did not (p=0.0001). Among the responders we noticed an increase of Ca 15–3 serum levels at progression. In particular, 5 pts had an increase of Ca 15–3 serum levels up to normal value when their disease progressed; 2 pts have not progressed yet and Ca 15–3 serum levels remain normal. Conclusions: We suggest that Ca 15–3 levels may be a prognostic factor to predict the response to EGFR inhibitors in pts with BAC. We are studying its role in a larger population with BAC and in other NSCLC subtypes as well. No significant financial relationships to disclose.

scholarly journals ASCO Provisional Clinical Opinion: Epidermal Growth Factor Receptor Mutation Testing in Practice

2011 ◽  
Vol 7 (3) ◽  
pp. 202-204 ◽  
Author(s):  
Mary Beth Beasley ◽  
Daniel T. Milton
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Mutation Testing ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Epidermal Growth

ASCO has recently provided guidance on emerging data on EGFR testing for the purpose of selecting first-line therapy for persons with advanced NSCLC through its Provisional Clinical Opinion.

scholarly journals Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xinghao Ai ◽  
Zhengbo Song ◽  
Hong Jian ◽  
Zhen Zhou ◽  
Zhiwei Chen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Growth Factor Receptor ◽  
Small Cell Lung ◽  
Open Label ◽  
Once Daily ◽  
Epidermal Growth ◽  
Exon 20 ◽  
Nsclc Patients

Abstract Background Standard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. The clinical benefits with pan-HER inhibitors (afatinib, neratinib, and dacomitinib), anti-HER2 antibody drug conjugate (ADC) trastuzumab emtansine, and an emerging irreversible tyrosine kinase inhibitor (TKI) poziotinib were modest. Another new ADC trastuzumab deruxtecan showed encouraging outcomes, but only phase I study was completed. Pyrotinib, another emerging irreversible epidermal growth factor receptor (EGFR)/HER2 dual TKI, has been approved in HER2-positive breast cancer in 2018 in China. It has shown promising antitumor activity against HER2-mutant NSCLC in phase II trials, but pyrotinib-related diarrhea remains an issue. The antiangiogenic and immunomodulatory drug thalidomide is a cereblon-based molecular glue that can induce the degradation of the IKAROS family transcription factors IKZF1 and IKZF3. The use of thalidomide can also decrease gastrointestinal toxicity induced by anti-cancer therapy. Methods This is an open-label, single-arm phase II trial. A total of 39 advanced NSCLC patients with HER2 exon 20 insertions and ≤ 2 lines of prior chemotherapy will be recruited, including treatment-naïve patients who refuse chemotherapy. Patients are allowed to have prior therapy with immune checkpoint inhibitors and/or antiangiogenic agents. Those who have prior HER2-targeting therapy or other gene alterations with available targeted drugs are excluded. Eligible patients will receive oral pyrotinib 400 mg once daily and oral thalidomide 200 mg once daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate. Discussion The addition of thalidomide to pyrotinib is expected to increase the clinical benefit in advanced NSCLC patients with HER2 exon 20 insertions, and reduce the incidence of pyrotinib-related diarrhea. We believe thalidomide is the stone that can hit two birds. Trial registration ClinicalTrials.gov Identifier: NCT04382300. Registered on May 11, 2020.

Soluble vascular endothelial growth factor receptor 2 (VEGFR2): New biomarker in advanced non-small cell lung cancer (NSCLC)?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22108-e22108 ◽  
Author(s):  
E. Sanmartin ◽  
E. Jantus Lewintre ◽  
R. Sirera ◽  
M. Miñana ◽  
A. Navarro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Vascular Endothelial ◽  
Time To Progression ◽  
Significant Difference ◽  
Nsclc Patients ◽  
Endothelial Growth Factor ◽  
Lower Expression

e22108 Background: An increase in VEGF expression in tumour or some blood compartments (i.e. serum or plasma) has been found in solid tumours of various origins. Several studies have suggested that ligands and receptors of the VEGFs/VEGFR system play an important role in tumour growth and is associated with metastasis and poor prognosis. The aim of our study was to investigate the usefulness of plasmatic VEGFR2 quantification as a new biomarker in advanced NSCLC. Methods: We studied 106 healthy controls (c) and 467 advanced NSCLC patients (p) (stage IIIB and IV) treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy and the plasmatic levels of the VEGFR2 were determined by ELISA. Results: In the NSCLC group, the median age was 59.9, range (31–80); 82% were males. The histological subtypes were: 31.4% squamous, 49.8% adenocarcinoma, 15.3% large cell and undifferentiated and 3.5% other. There was a significant difference in the plasmatic levels of VEGFR2 between c and p (mean± SEM): 6318±152 ng/ml and 8141± 119 ng/ml, respectively (p<0.0001). On the other hand, we found no statistical differences according to sex, histology, or stage. The area under the ROC curve was 0.743 indicating that VEGFR2 is an adequate biomarker for the discrimination between c and p. Dividing the cohort in two subgroups according to VEGFR2 levels: high (>9473,9 ng/ml) and low (≤ 9473,9 ng/ml), we found significant difference in terms of Time to Progression (TTP). Patients with higher levels of VEGFR2 had a median TTP of 204 days whereas in the group with lower expression the median was 164 days, (p= 0.039). Conclusions: In advanced NSCLC, we found higher levels of soluble VEGFR2 in p than in c. There was a correlation between higher expressions of soluble VEGFR2 with better prognosis, in terms of TTP, therefore a more thorough understanding in the role of the plasmatic quantification of this angiogenic receptor in advanced NSCLC p seems to be an important task. No significant financial relationships to disclose.

scholarly journals Efficacy of Osimertinib in NSCLC Harboring Uncommon EGFR L861Q and Concurrent Mutations: Case Report and Literature Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruiting Lin ◽  
Ruilian Chen ◽  
Zhiqiang Chen ◽  
Leihao Hu ◽  
Wei Guo ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Free Survival ◽  
First Line Therapy ◽  
Epidermal Growth ◽  
Good Treatment Option ◽  
Nsclc Patients ◽  
First And Second Generation ◽  
Egfr Tkis

The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on the efficacy of osimertinib in NSCLC patients with uncommon mutations. Here, we report the case of a 68-year-old man with advanced NSCLC with concurrent EGFR L861Q mutation as well as TP53 and RB1 mutations. The patient was treated with osimertinib as first-line therapy and achieved a remarkable progression-free survival of 15 months. His symptoms were significantly alleviated and the dose was well tolerated. The findings of the present study indicate that osimertinib might be a good treatment option for NSCLC patients with the L861Q mutation.

Prophylactic cranial irradiation after reaching complete response, partial response, or stable disease in non-small cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (ProACT).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS7617-TPS7617
Author(s):  
Amanda Tufman ◽  
Claus Belka ◽  
Heike Kuenzel ◽  
Rudolf M. Huber
Keyword(s):  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Complete Response ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Epidermal Growth ◽  
Nsclc Patients ◽  
Egfr Tkis

TPS7617 Background: Patients with non-small cell lung cancer (NSCLC) who respond to treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) seem to be at increased risk of central nervous system relapse, and may benefit from prophylactic cranial irradiation (PCI) more than other NSCLC patients. Methods: This study investigates the safety and efficacy of combining PCI with EGFR TKIs in stage IV NSCLC. Patients with stage IV NSCLC, no evidence of brain metastases, and an indication for first or later line therapy with an EGFR TKI will be enrolled. Those with complete response (CR), partial response (PR), or stable disease (SD) following 6 weeks of therapy and no evidence of brain metastases on MRI will be treated with PCI. Neurocognitive function, depression indices, quality of life, symptoms, and ability to function independantly will be assessed at baseline, before PCI, and at 6 week and then 3 month intervals following PCI. MRI will be repeated 6 weeks following PCI and at 3 month intervals, and serum markers of blood brain barrier permeability (neuron-specific enolase (NSE), protein S100 beta) will be assessed at all visits. Safety data will be formally reviewed after the first 10 patients. The primary endpoint for efficacy is overall survival. Secondary endpoints include progression free survival, site of progression, quality of life and neurological disability. Planed subgroup analyses based on mutation status, line of treatment with TKIs, comorbidity, precise histology and molecular biology will be carried out.

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