scholarly journals ERβ localization influenced outcomes of EGFR-TKI treatment in NSCLC patients with EGFR mutations

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Zhijie Wang ◽  
Zhenxiang Li ◽  
Xiaosheng Ding ◽  
Zhirong Shen ◽  
Zhentao Liu ◽  
...  
Keyword(s):  
Egfr Mutations ◽  
Tki Treatment ◽  
Nsclc Patients ◽  
Egfr Tki

scholarly journals Non-classic EGFR mutations in a cohort of Dutch EGFR-mutated NSCLC patients and outcomes following EGFR-TKI treatment

2016 ◽  
Vol 115 (12) ◽  
pp. 1504-1512 ◽  
Author(s):  
J L Kuiper ◽  
S M S Hashemi ◽  
E Thunnissen ◽  
P J F Snijders ◽  
K Grünberg ◽  
...  
Keyword(s):  
Egfr Mutations ◽  
Tki Treatment ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki

Impact of EGFR mutation status on clinical outcome of nintedanib plus docetaxel in patients with previously treated non-small cell lung cancer (NSCLC): Retrospective analysis of Korean nintedanib named-patient usage (NPU) program in NSCLC (KCSG LU14-2).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20638-e20638
Author(s):  
Sook-hee Hong ◽  
Ho Jung An ◽  
Yun-Gyoo Lee ◽  
Hoon-Kyo Kim ◽  
Seung-Sei Lee ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Egfr Mutations ◽  
Clinical Activity ◽  
Good Tolerability ◽  
Mutation Status ◽  
Tki Treatment ◽  
Nsclc Patients ◽  
Egfr Tki

e20638 Background: Anti-angiogenic agents have been reported to have clinical activity for NSCLC harboring EGFR mutation (mutEGFR) with/without EGFR Tyrosine kinase inhibitor (TKI). We report clinical outcomes of nintedanib plus docetaxel for refractory NSCLC patients conducted by virtue of Korean NPU program. Methods: Patients with NSCLC were eligible if they failed at least one prior systemic treatment. Docetaxel was administered with 75 or 60mg/m2 on D1 or 37.5mg/m2 on D1, D8 every 3 weeks plus nintedanib 200mg orally twice daily. Nintedanib treatment was continued until disease progression or unacceptable toxicity after 4-6 cycles of combination therapy. Results: Of 62 patients enrolled, 23 patients had activating EGFR mutations (14 in exon19 deletion, 7 exon21 L858R/L861Q, 1 exon20 duplication, and 1 in both exon19 deletion and exon20 T790M) and progressed during prior EGFR-TKI treatment. Of 23 patients, 22 had progressed during or after platinum doublet chemotherapy. Only for 2 patients, EGFR mutation status was unknown. The majority of patients were heavily pretreated, with 43.7% received nintedanib plus docetaxel as ≥ 4th line therapy. 4 patients had prior bevacizumab treatment. Objective response rate (ORR) was 22.9%. Median PFS and OS were 3.9 months (95% CI 3.1-4.6) and 9.5 months (95% CI 5.3-13.7), respectively. Depending on EGFR mutation status, ORR in mutEGFR group was higher than wtEGFR group (30.4% vs 20%, p= 0.50) and median PFS in mutEGFR group was significantly longer than wtEGFR group (6.1 vs 3.3 months, p= 0.008). No treatment related death was reported. Common grade 3/4 adverse events were neutropenia (58.3%) and reversible elevated liver enzyme (18.8%). Conclusions: Taken together, nintedanib plus docetaxel showed meaningful clinical activity with good tolerability for refractory NSCLC patients. Our data suggest that this combination may be a recommendable regimen for EGFR-TKI-resistant mutEGFR NSCLC.

EGFR-TKI after disease progression with central nervous system metastasis in advanced non-small cell lung cancer with EGFR mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19083-e19083
Author(s):  
Takashi Sone ◽  
Kazuo Kasahara ◽  
Koji Kurokawa ◽  
Asao Sakai ◽  
Toshiyuki Kita ◽  
...  
Keyword(s):  
Good Prognosis ◽  
Egfr Mutations ◽  
Group Differences ◽  
Cns Metastasis ◽  
Free Treatment ◽  
Never Smokers ◽  
Tki Treatment ◽  
A Prospective Study ◽  
Nsclc Patients ◽  
Egfr Tki

e19083 Background: Several retrospective studies have reported that continued treatment with EGFR-TKI after developing progressive disease (PD) by RECIST improved survival compared to TKI-free treatment in NSCLC patients with EGFR mutations. However, it is unclear which patients would benefit from EGFR-TKI after PD. We hypothesized that patients with CNS progression only, without systemic deterioration, would show a good prognosis with EGFR-TKI after PD. Methods: In order to clarify the survival benefits in patients treated by EGFR-TKI after developing PD, particularly patients with CNS metastasis alone, NSCLC patients with EGFR mutations who were treated with EGFR-TKI and showed progression were analyzed retrospectively. The patients were categorized into two groups: patients continuing with EGFR-TKI treatment after progression (continuation group) and patients switched to chemotherapy or BSC (discontinuation group). Patients were also classified into two groups by site of progression: patients who showed deterioration involving only CNS metastasis (CNS group) and patients who showed progression of the primary lesion, lymph nodes, bone, liver, adrenal glands, CNS, or other sites (systemic group). Differences in post-EGFR-TKI progression survival (PPS) and overall survival were compared between the groups. Results: A total of 75 patients, including 54 women, 56 never smokers, 73 patients with adenocarcinomas, and 57 patients with good PS (0, 1), were analyzed. There were 40 patients with deletions in exon 19, 29 patients with L858R, and 6 with minor mutations. The continuation group (n=36) had a significantly longer PPS than the discontinuation group (n=39) (16.2 m vs. 8.5 m, p<0.01). Although it was not significant, the CNS group (n=14) showed longer PPS than the systemic group (n=61) (17.3 m vs. 9.2 m, p=0.10). The PPS of 9 patients (continuation and CNS groups) was 21.0 m, while PPS of 34 patients (discontinuation and systemic group) was 7.2 m. Conclusions: In this retrospective analysis, continued treatment with EGFR-TKI after PD resulted in longer PPS. A prospective study of patients with progression involving only CNS metastasis treated with EGFR-TKI is needed.

scholarly journals Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury

2021 ◽  
Vol 22 (2) ◽  
pp. 792
Author(s):  
Tohru Ohmori ◽  
Toshimitsu Yamaoka ◽  
Koichi Ando ◽  
Sojiro Kusumoto ◽  
Yasunari Kishino ◽  
...  
Keyword(s):  
Lung Injury ◽  
Tyrosine Kinase ◽  
Performance Status ◽  
Cytotoxic Agents ◽  
Egfr Mutations ◽  
Poor Performance Status ◽  
Chronic Obstructive ◽  
Tki Treatment ◽  
Egfr Tki ◽  
Egfr Tkis

The tyrosine kinase activity of epidermal growth factor receptors (EGFRs) plays critical roles in cell proliferation, regeneration, tumorigenesis, and anticancer resistance. Non-small-cell lung cancer patients who responded to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and obtained survival benefits had somatic EGFR mutations. EGFR-TKI-related adverse events (AEs) are usually tolerable and manageable, although serious AEs, including lung injury (specifically, interstitial lung disease (ILD), causing 58% of EGFR-TKI treatment-related deaths), occur infrequently. The etiopathogenesis of EGFR-TKI-induced ILD remains unknown. Risk factors, such as tobacco exposure, pre-existing lung fibrosis, chronic obstructive pulmonary disease, and poor performance status, indicate that lung inflammatory circumstances may worsen with EGFR-TKI treatment because of impaired epithelial healing of lung injuries. There is limited evidence from preclinical and clinical studies of the mechanisms underlying EGFR-TKI-induced ILD in the available literature. Herein, we evaluated the relationship between EGFR-TKIs and AEs, especially ILD. Recent reports on mechanisms inducing lung injury or resistance in cytokine-rich circumstances were reviewed. We discussed the relevance of cytotoxic agents or immunotherapeutic agents in combination with EGFR-TKIs as a potential mechanism of EGFR-TKI-related lung injury and reviewed recent developments in diagnostics and therapeutics that facilitate recovery from lung injury or overcoming resistance to anti-EGFR treatment.

Impact of HER2 expression on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS study subset analysis

Lung Cancer ◽  
2020 ◽  
Vol 150 ◽  
pp. 83-89
Author(s):  
Kadoaki Ohashi ◽  
Kiichiro Ninomiya ◽  
Hiroshige Yoshioka ◽  
Akihiro Bessho ◽  
Takuo Shibayama ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Lung Tumors ◽  
Egfr Mutations ◽  
Her2 Expression ◽  
Subset Analysis ◽  
Tki Treatment ◽  
Egfr Tki

Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC

Lung Cancer ◽  
2020 ◽  
Vol 139 ◽  
pp. 133-139 ◽  
Author(s):  
Shuo Yang ◽  
Shiqi Mao ◽  
Xuefei Li ◽  
Chao Zhao ◽  
Qian Liu ◽  
...  
Keyword(s):  
Lower Incidence ◽  
Advanced Nsclc ◽  
Egfr Mutations ◽  
T790m Mutation ◽  
Tki Treatment ◽  
Egfr Tki

scholarly journals The Clinical Significance of RAS, PIK3CA, and PTEN Mutations in Non-Small Cell Lung Cancer Using Cell-Free DNA

2020 ◽  
Vol 9 (8) ◽  
pp. 2642
Author(s):  
Won Jin Chang ◽  
Jae Sook Sung ◽  
Sung Yong Lee ◽  
Eun Joo Kang ◽  
Nak-Jung Kwon ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Stage Iv ◽  
Egfr Mutations ◽  
Sequencing Analysis ◽  
Downstream Signaling ◽  
Pathway Activation ◽  
Activating Egfr Mutation ◽  
Tki Treatment ◽  
Deep Sequencing Analysis ◽  
Egfr Tki

Mutations in the EGFR gene downstream signaling pathways may cause receptor-independent pathway activation, making tumors unresponsive to EGFR inhibitors. However, the clinical significance of RAS, PIK3CA or PTEN mutations in NSCLC is unclear. In this study, patients who were initially diagnosed with NSCLC or experienced recurrence after surgical resection were enrolled, and blood samples was collected. Ultra-deep sequencing analysis of cfDNA using Ion AmpliSeq Cancer Hotspot Panel v2 with Proton platforms was conducted. RAS/PIK3CA/PTEN mutations were frequently detected in cfDNA in stage IV NSCLC (58.1%), and a high proportion of the patients (47.8%) with mutations had bone metastases at diagnosis. The frequency of RAS/PIK3CA/PTEN mutations in patients with activating EGFR mutation was 61.7%. The median PFS for EGFR-TKIs was 15.1 months in patients without RAS/PIK3CA/PTEN mutations, and 19.9 months in patients with mutations (p = 0.549). For patients with activating EGFR mutations, the overall survival was longer in patients without RAS/PIK3CA/PTEN mutations (53.8 months vs. 27.4 months). For the multivariate analysis, RAS/PIK3CA/PTEN mutations were independent predictors of poor prognosis in patients with activating EGFR mutations. In conclusion, RAS, PIK3CA and PTEN mutations do not hamper EGFR-TKI treatment outcome; however, they predict a poor OS when activating EGFR mutations coexist.

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