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.

scholarly journals Tetracyclines increase the survival of NSCLC patients treated with EGFR TKIs: a retrospective nationwide registry study

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000864
Author(s):  
Virve Alanen ◽  
Sanna Iivanainen ◽  
Martti Arffman ◽  
Jussi Pekka Koivunen
Keyword(s):  
Second Generation ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Epidermal Growth ◽  
Prophylactic Use ◽  
Nsclc Patients ◽  
First And Second Generation ◽  
Egfr Tki ◽  
Egfr Tkis

BackgroundWith the first and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), clinical benefit and rash correlate together. EGFR TKI-induced rash can be alleviated with tetracyclines, but it is unknown whether the use of tetracyclines can increase the survival of non-small-cell lung cancer (NSCLC) patients treated with EGFR TKIs.MethodsWe collected all the patients (n=1271) who had reimbursement for EGFR TKIs (gefitinib, erlotinib and afatinib) in Finland 2011–2016, had purchased TKIs, and had data available at nationwide cancer registry. The survival was analysed from the first EGFR TKI purchase to death or end-of follow-up, and patients were stratified according to TKIs, purchases of antibiotics, their ATC class and timing.Results802 (63.1%) patients had antibiotic purchases −14 to +200 days from the first EGFR TKI purchase, 447 of these tetracyclines. 322 (25.3%) had had purchased antibiotics −14 to +14 days (prophylaxis) from the first EGFR TKI purchase, 188 of these tetracyclines. Purchase of antibiotics was associated with improved survival (HR 0.80, 95% CI 0.71 to 0.91), which limited to tetracycline purchases only (HR 0.72, 95% CI 0.64 to 0.82). The largest survival benefit was seen with the prophylactic use of tetracyclines (HR 0.74, 95% CI 0.62 to 0.88). The benefit from tetracyclines was limited to erlotinib only (HR 0.68, 95% CI 0.58 to 0.78) which was retained in multivariate analysis. Prophylactic use of tetracyclines was associated with a longer erlotinib treatment duration (HR 0.81, 95% CI 0.61 to 0.96) but not with dose reductions or treatment breaks.ConclusionsTetracyclines improve the survival of NSCLC patients treated with the first and second-generation EGFR TKIs and they should be considered as a prophylaxis when initiating EGFR TKIs with high incidence of rash.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

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 Successful treatment of a patient with NSCLC carrying uncommon compound EGFR G719X and S768I mutations using osimertinib: A case report

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092879
Author(s):  
Yangyang Cai ◽  
Yizhuo Wang ◽  
Jingnan Sun ◽  
Xu Wang ◽  
Yinghui Xu ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Postoperative Outcome ◽  
Postoperative Recurrence ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
First And Second Generation ◽  
Egfr Tkis

The discovery of epidermal growth factor receptor ( EGFR) somatic mutations and the availability of tyrosine kinase inhibitors (TKIs) as targeted therapies have altered the therapeutic prospects of advanced non-small-cell lung cancer (NSCLC). G719X and S768I are uncommon mutations, and they often exist as compound mutations. A few reports have described the efficacy of first- and second-generation EGFR-TKIs. However, the efficacy of osimertinib in patients with these uncommon compound mutations is unknown. In this study, we reported the postoperative outcome of a patient with NSCLC and uncommon compound EGFR G719X and S768I mutations. After postoperative recurrence, the patient was treated with osimertinib, and an excellent and long-lasting clinical response was achieved. The patient has taken osimertinib for 31.0 months and exhibited a partial response, and her follow-up is ongoing.

RAS mutations and their correlation with survival of patients with advanced pancreatic adenocarcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 325-325
Author(s):  
Thiago Lins Almeida ◽  
Jessica Ribeiro Gomes ◽  
Marcel Cerqueira Cesar Machado ◽  
Antonio C. Buzaid ◽  
Fernando C. Maluf
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Predictive Factor ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Free Survival ◽  
First Line Therapy ◽  
Ras Status ◽  
Epidermal Growth

325 Background: The prognosis of pancreatic adenocarcinoma (PA) remains poor despite FOLFIRINOX and nab-paclitaxel-gemcitabine based chemotherapy. The epidermal growth factor receptor (EGFR) has a major role in pancreatic cancer carcinogenesis.The RAS status showed to be a predictive factor for response to anti-EGFR therapy in colon cancer. We aim to analyze the K-RAS and N-RAS status in PA and its prognostic impact. Methods: Retrospective analysis included 24 patients with metastatic (67%) or locally advanced (29%) PA at diagnosis (AEMOC, Brazil). K-RAS and N-RAS profile were performed by polymerase chain reaction and bidirectional sequencing (codons 12, 13, 61, 117, 146). The results were then analyzed in regards to overall survival (OS) and progression-free survival (PFS) in PA. Results: The sample showed: median age of 63 years (28-86), 62.5% male, 45.8% smoker, head site (67%), ductal (68%), and mild differentiation features (45%). The first-line therapy was FOLFIRINOX (62.5%) and gemcitabine (33.3%). The median PFS and OS were 6.5 and 13 months (mo), respectively. Nineteen patients (79.1%) presented mutation in K-RAS: four c.35G>A (G12D), four c.34G>C (G12R), four c.35G>T (G12V), three c.35G>C (G12A), one c.437C>T (A146V), and one c.34G>T (G12C). Mutation in N-RAS (c.38G>A (G13D) was detected in only one patient (4%). The only independent factor for survival was K-RAS status: the c.35G>A (G12D) polymorphism yielded worse PFS and OS when compared to non-c.35G>A (G12D) mutation: 3 vs 7 mo [HR 0.25, 95% CI, (0.04–1.63)] for PFS (p<0,0043) and 3.5 vs13 mo [HR 0.17, 95% CI, 0.01-1.58)] for OS (p<0,0001), respectively. Conclusions: K-RAS was the only prognostic factor for PFS and OS, with the polymorphism c.35G>A (G12D) being related to a worse prognostic. Further studies are necessary to better evaluate whether K-RAS and N-RAS status is prognostic and/or predictive factor.

scholarly journals A Lung Adenocarcinoma Patient With a Rare EGFR E709_T710delinsD Mutation Showed a Good Response to Afatinib Treatment: A Case Report and Literature Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Wei ◽  
Yueli Cui ◽  
Yao Guo ◽  
Lei Li ◽  
Liang Zeng
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Insertion Mutation ◽  
Lung Cancer Patients ◽  
First Line Therapy ◽  
Lung Adenocarcinoma Patient ◽  
Epidermal Growth ◽  
L858r Mutation

For advanced lung adenocarcinoma patients with common epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or the exon 21 L858R mutation), tyrosine kinase inhibitors (TKIs) are the standard therapies, and achieve favorable responses. However, for the rare EGFR deletion-insertion mutation of exon 18, there is no evidence of the efficacy of EGFR TKIs. Herein, we report a lung adenocarcinoma patient harboring a rare EGFR E709_T710delinsD mutation who was treated with afatinib as the first-line therapy and achieved a progression-free survival of 23 months. After the disease progressed, the patient received almonertinib treatment and exhibited a stable disease. This case indicated that non-small cell lung cancer patients harboring the EGFR E709_T710delinsD mutation could benefit from afatinib treatment, followed with almonertinib treatment, as a potential therapeutic strategy.

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.

scholarly journals Case Report: Long Progression-Free Survival of Immunotherapy for Lung Adenocarcinoma With Epidermal Growth Factor Receptor Mutation

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianfeng Peng ◽  
Xianguang Zhao ◽  
Kaikai Zhao ◽  
Xiangjiao Meng
Keyword(s):  
Case Report ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
T790m Mutation ◽  
Free Survival ◽  
Epidermal Growth ◽  
L858r Mutation ◽  
Egfr Tkis

BackgroundImmune checkpoint inhibitors (ICIs) have been clinically proven to be efficient in non-small cell lung cancer (NSCLC). However, it has also been found that immunotherapy is not effective for all patients. For instance, some patients with epidermal growth factor receptor (EGFR) mutation tumors have a low overall response rate to ICIs. As a result, we retrospectively analyzed the efficacy of anti-programmed death-ligand 1 (anti-PD-L1) blockade (atezolizumab) treatment for a patient with EGFR mutation, and we explored the interaction between immunotherapy and EGFR mutations in NSCLC.Case PresentationA patient, 62-year-old non-smoking female, with lung adenocarcinoma was initially misdiagnosed as EGFR wild type and received a third-line treatment with atezolizumab, experiencing partial response (PR) and progression-free survival (PFS) for 23 months. She had later been confirmed with EGFR L858R mutation prior to taking atezolizumab. On top of that, the patient developed T790M mutation after being administered with atezolizumab instead of EGFR tyrosine kinase inhibitors (TKIs). She started with osimertinib, although the lesion continued to progress. Tumor mutational burden (TMB), PD-L1 expression, and tumor-infiltrating lymphocytes (TILs) had been tested for further analysis.ConclusionThe case report and literature review indicate that ICIs might be more effective for L858R mutation than for other EGFR mutant subtypes, which correlates with certain potential predictors such as TMB and concurrent PD-L1 plus CD8+ TIL expression. However, there is no report on progression from non-primary EGFR T790M mutation to T790M mutation of patients who neither previously suffered from EGFR-TKIs nor responded to osimertinib. This case report will offer some information to guide the investigation on how to identify those who can benefit from immunotherapy and those who do not respond to EGFR-TKIs among the patients with EGFR mutations.

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