scholarly journals Clinical Characteristics and Survival Outcomes for Non-Small-Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Double Mutations

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Min Peng ◽  
Yi Ming Weng ◽  
Hua Li Liu ◽  
Gui Fang Yang ◽  
Yi Yao ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Tki Treatment ◽  
Egfr Tki ◽  
Egfr Tkis

Multiple randomized clinical trials have demonstrated that epidermal growth factor receptor (EGFR) exon 19 deletion (19Del) and exon 21 L858R mutation (L858R) are highly correlated with sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in non-small-cell lung cancer (NSCLC). A mutation in exon 20 (T790M) is reportedly associated with resistance to EGFR-TKIs. However, few studies have focused on patients harboring double mutations in these 3 mutation sites. In this retrospective study, forty-five patients (45/2546, 1.7%) harbored double mutations of 19Del, L858R, and T790M. Twenty-four patients with EGFR double mutations received EGFR-TKI therapy. Clinical characteristics of these patients, including the response to EGFR-TKIs and progression-free survival outcome for EGFR-TKI treatment (PFS-TKI), were analyzed. Patients with EGFR double mutations were more likely to be nonsmokers, have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1, have adenocarcinoma, and be at stage III-IV. The ORR, DCR, and median PFS-TKI in patients harboring EGFR double mutations were lower than in patients with a single EGFR-activating mutation. The differences in ORR and DCR were statistically insignificant between the 3 groups. Patients with double mutations of 19Del and T790M had longer PFS-TKIs than patients in the other 2 groups.

scholarly journals The Evolving Role of Maintenance Therapy Using Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) in the Management of Advanced Non-Small-Cell Lung Cancer

2012 ◽  
Vol 6 ◽  
pp. CMO.S5127 ◽  
Author(s):  
Chao H. Huang ◽  
Benjamin C. Powers
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Small Cell Lung Cancer ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Egfr Tkis

The epidermal growth factor receptor (EGFR) plays an important role in the development of many cancers, including non-small cell lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are a class of novel biologically-targeted agents widely used in the management of recurrent non-small cell lung cancer. Erlotinib, one of the EGFR TKIs, is currently FDA approved in second and third line therapy. However, recent studies showed that erlotinib is also effective as maintenance therapy after initial chemotherapy, improving disease free survival and possibly overall survival. Our current understanding of erlotinib's mechanism of action, with the discovery that EGFR mutation confers higher response rate, has propelled this agent into the first line setting. Advances in molecular testing and clinical research of this agent and other agents in this class will eventually change the way we utilize EGFR TKIs in the near future.

scholarly journals Effect of Osimertinib in Combination With Chemotherapy and Bevacizumab for Untreated Epidermal Growth Factor Receptor–Mutated Advanced Non-Small-Cell Lung Cancer: Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Haifeng Qin ◽  
Fang Wang ◽  
Zhen Zeng ◽  
Suting Jia ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Small Cell Lung Cancer ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Egfr Tki

Introduction: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. However, whether patients with EGFR mutations can be treated by osimertinib in combination with conventional therapies, remains unknown.Case presentation: We treated a 67-year-old female diagnosed with non-small-cell lung cancer with an EGFR 21 exon L858R–positive mutation. The patient was treated with 80 mg orally administered osimertinib daily, 830 mg pemetrexed, 120 mg cisplatin, and 500 mg bevacizumab. After two cycles of therapy, the patient’s intrapulmonary lesions shrank from 18 × 24 mm to 16 × 4 mm. Moreover, two cycles of evaluation were PR, and four cycles of confirmation were PR. The patient continued to receive the treatments and tolerated them well.Conclusions: The patient benefited from treatment with osimertinib in combination with chemotherapy and bevacizumab.

scholarly journals Final Results from a Phase II Trial of Osimertinib for Elderly Patients with Epidermal Growth Factor Receptor t790m-Positive Non-Small Cell Lung Cancer That Progressed during Previous Treatment

2020 ◽  
Vol 9 (6) ◽  
pp. 1762 ◽  
Author(s):  
Akira Nakao ◽  
Osamu Hiranuma ◽  
Junji Uchino ◽  
Chikara Sakaguchi ◽  
Tomoyuki Araya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Phase Ii Trial ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Tki Treatment ◽  
Egfr Tki ◽  
Egfr Tkis

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used for treating EGFR-mutated lung cancer, and osimertinib is effective in cases that acquired T790M mutations after treatment with the first- and second-generation EGFR-TKIs. However, no study has evaluated its safety and efficacy in older patients. This phase II trial (jRCTs071180002) evaluated osimertinib in T790M mutation-positive Japanese patients who were ≥75 years old and had experienced relapse or progression after previous EGFR-TKI treatment. Our previous report that enrolled 36 patients showed the overall response rate (58.3%) and disease control rate (97.2%), while this report describes the results for the progression-free survival (PFS), overall survival (OS), and safety analyses. The median PFS was 11.9 months (95% confidence interval (CI): 7.9–17.5), and the median OS was 22.0 months (95% CI: 16.0 months–not reached). The most frequent adverse events were anemia/hypoalbuminemia (27 patients, 75.0%), thrombocytopenia (21 patients, 58.3%), and paronychia/anorexia/diarrhea/neutropenia (15 patients, 41.7%). Pneumonitis was observed in four patients (11.1%), including two patients (5.6%) with Grade 3–4 pneumonitis. These results suggest that osimertinib was relatively safe and effective for non-small cell lung cancer that acquired T790M mutations after previous EGFR-TKI treatment, even among patients who were ≥75 years old.

scholarly journals IGFBP7 Drives Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition in Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 36 ◽  
Author(s):  
Shang-Gin Wu ◽  
Tzu-Hua Chang ◽  
Meng-Feng Tsai ◽  
Yi-Nan Liu ◽  
Chia-Lang Hsu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Tki Resistance ◽  
Epidermal Growth ◽  
Tki Treatment ◽  
Egfr Tki ◽  
Egfr Tkis

Patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer show a dramatic response to EGFR-tyrosine kinase inhibitors (TKIs). However, acquired drug resistance eventually develops. This study explored the novel mechanisms related to TKI resistance. To identify the genes associated with TKI resistance, an integrative approach was used to analyze public datasets. Molecular manipulations were performed to investigate the roles of insulin-like growth factor binding protein 7 (IGFBP7) in lung adenocarcinoma. Clinical specimens were collected to validate the impact of IGFBP7 on the efficacy of EGFR TKI treatment. IGFBP7 mRNA expression in cancer cells isolated from malignant pleural effusions after acquired resistance to EGFR-TKI was significantly higher than in cancer cells from treatment-naïve effusions. IGFBP7 expression was markedly increased in cells with long-term TKI-induced resistance compared to in TKI-sensitive parental cells. Reduced IGFBP7 in TKI-resistant cells reversed the resistance to EGFR-TKIs and increased EGFR-TKI-induced apoptosis by up-regulating B-cell lymphoma 2 interacting mediator of cell death (BIM) and activating caspases. Suppression of IGFBP7 attenuated the phosphorylation of insulin-like growth factor 1 receptor (IGF-IR) and downstream protein kinase B (AKT) in TKI-resistant cells. Clinically, higher serum IGFBP7 levels and tumors with positive IGFBP7-immunohistochemical staining were associated with poor TKI-treatment outcomes. IGFBP7 confers resistance to EGFR-TKIs and is a potential therapeutic target for treating EGFR-TKI-resistant cancers.

scholarly journals A Comparison Between First-, Second- and Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small-Cell Lung Cancer and Brain Metastases

2021 ◽  
Vol 2 (1) ◽  
pp. 1-10
Author(s):  
Salvatore Caponnetto ◽  
Ornella Cantale ◽  
Alex Friedlaender ◽  
Fabio Gomes ◽  
Sunil Daryanani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Egfr Tkis

Patients with non-small-cell lung cancer (NSCLC), harboring Epidermal Growth Factor Receptor (EGFR) mutations, are more susceptible to brain metastases (BM). Comparisons of the efficacy of different-generation EGFR-tyrosine kinase inhibitors (TKI) on BMs from NSCLC are currently limited. We identified studies comparing different EGFR-TKIs for NSCLC through Pubmed literature search and selected those with neurological outcome data. By two retrospective analyses, Erlotinib showed longer neurological time-to-progression (30 months vs. 15.8 months, P = 0.024) and reduced the risk of central nervous system (CNS) progression (Hazard Ratio (HR) 0.25; 95% CI, 0.08–0.81; P = 0.021) compared to Gefitinib. In a phase 2b randomized trial, 16% of patients with BMs had a similar Progression Free Survival (PFS) (HR 0.76, 95% CI 0.41–1.44) or Overall Survival (OS) (HR 1.16, 95% CI 0.61–2.21) with Afatinib versus Gefitinib; a lower risk of developing subsequent BMs with Afatinib than Gefitinib (HR 0.49; 95% CI 0.34–0.71; P < 0.001) was reported by a retrospective study. A randomized phase 3 trial proved that patients with BMs treated with Osimertinib had longer PFS (HR 0.47, 95% CI 0.30–0.74) and OS (HR 0.79, 95% CI 0.61–1.01) than with Gefitinib, and lower incidence of CNS progression (6% vs. 15%, respectively). Although there is limited evidence, differences in CNS activity may exist between EGFR-TKIs.

scholarly journals Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer and Choroidal Metastases: Long-Term Outcome and Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

2020 ◽  
Author(s):  
Clémentine Bouchez ◽  
Johan Pluvy ◽  
Ghassen Soussi ◽  
Marina Nguenang ◽  
Solenn Brosseau ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Choroidal Metastasis ◽  
Epidermal Growth ◽  
Egfr Mutant ◽  
Egfr Tki

Abstract Background: Although previously reported, little is known about choroidal metastasis in Epidermal Growth Factor Receptor (EGFR)-mutant Non-small cell lung cancer (NSCLC). Methods: In this single-center retrospective cohort including 83 consecutive metastatic EGFR-mutant NSCLC patients, from Sept. 2015 to Oct. 2018, six exhibited symptomatic choroidal metastases. All brain MRI scans performed in the EGFR-mutant patients were reviewed, with one case of asymptomatic choroidal metastasis identified. Kaplan-Meier analysis and log-rank test were conducted to assess median overall survival (OS) from diagnosis for the two groups, with or without choroidal metastases.Results: Prevalence of choroidal metastases in EGFR-mutated NSCLCs was 8.4% (7/83). Five were women, and four current or former smokers. Molecular analysis showed three tumors with exon 19 deletion, three with L858R mutation, and one with complex exon 21 mutation. The choroidal metastases were symptomatic in six/seven patients. Visual disturbances decreased in all but one symptomatic cases upon EGFR TKI, and the choroidal response was maintained over time. Median follow-up was 42.2 mo (95%CI [37.2 - 47.1]). Median OS in the choroidal metastasis group was 23.4 mo (95%CI [0.1 - 51.4]) versus 27.9 mo (95%CI [16.9 - 38.9]) in the non-choroidal metastasis group (p=0.32). In the choroidal metastasis group, 2-year and 5-year OS were 47.6% and 0%, respectively, versus 55.8% and 26.3% in the non-choroidal metastasis subset.Conclusions: Choroidal metastases in NSCLC EGFR-mutant patients are rare but should be systematically suspected in case of visual disturbance. TKIs are efficient for treating visual symptoms. Whether choroidal metastases confer a worse prognosis remains unclear owing to the third-generation EGFR TKI osimertinib first-line registration.

Sign in / Sign up

Export Citation Format

Share Document