Tyrosine kinase inhibitors (TKI) treatment of non-small cell lung cancer (NSCLC) patients (p) based on EGFR mutations (m) status in serum only.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19088-e19088
Author(s):  
Laia Capdevila ◽  
Enric Carcereny ◽  
Itziar de Aguirre ◽  
Sara Cros ◽  
Cristina Queralt ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Complete Response ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Molecular Alterations ◽  
Former Smokers ◽  
Tki Treatment ◽  
Ecog Ps ◽  
Egfr Mutated ◽  
Egfr Tki

e19088 Background: Treatment of EGFR mutated NSCLC p with EGFR TKIs in phase III trials has shown improved efficacy to standard chemotherapy. However, it can be difficult to obtain sufficient tumor tissue for analysis of EGFR m status in a large proportion of p. Nevertheless, so far, no data exists for NSCLC p treated according to EGFR m status in serum alone. Methods: We reviewed our database to identify EGFR mutated p, excluding those for whom status was available in both serum and tissue. We analyzed p treated with an EGFR TKI for whom EGFR m status was known in serum only (status in tissue unknown due to insufficient material). At the same time, we reviewed p in whom EGFR m status in tissue was available over the same period in order to compare clinical characteristics and efficacy parameters: PFS, ORR and overall survival (OS). EGFR m analysis was performed in cell free circulating DNA (cfDNA)isolated from serum and plasma using the QIAmp DNA blood mini kit. Results: 9 p with EGFR m detected in serum and 33 p with EGFR m in tissue were included. In EGFR mutated p in serum, median age 63; male 55.6%; non-smokers 33.3%; former smokers 44.4%; ECOG PS 0-1 66.7%; adenocarcinoma 77.8%; deletion19 33.3%, L858R 66.7%; EGFR TKI treatment in 1st line 44.4%; 2nd or 3rd line 55.6%. ORR: complete response (CR) 22.2%; partial response (PR) 22.2%; stable disease (SD) 22.2%; progressive disease (PD) 11.1%. 2p had poor PS and died prior to evaluation. mPFS 4.7 months (mo). mOS 18 mo. In p with EGFR m in tissue, median age 61; male 36.4%; non-smokers 75.8%; former smokers 24.2%; adenocarcinoma 87.9%; deletion19 75.8%; L858R 24.2%; 1st line 54.5%; 2nd or 3rd line 45.5%. ORR: CR 15.2%; PR 57.6%; SD 12.1%; PD 15.2%. mPFS 8.9 mo. mOS 32.7 mo. The multivariate analysis for OS considering EGFR m in serum differed according to PS (PS 0-1 16.6 mo vs PS > 2 5.2 mo). Conclusions: Obtaining sufficient tissue from NSCLC p for analysis of EGFR m status and other molecular alterations can be difficult. Determination of EGFR m in serum alone is feasible, yields similar results to mutation status in tissue, and could permit us to take treatment decisions.

Impact of HER2 aberrations on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS STUDY subset analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9056-9056 ◽  
Author(s):  
Hiroe Kayatani ◽  
Keisuke Aoe ◽  
Kadoaki Ohashi ◽  
Hiroshige Yoshioka ◽  
Akihiro Bessho ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Her2 Protein ◽  
Epidermal Growth ◽  
Tki Treatment ◽  
Egfr Mutant ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr Tkis

9056 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a key treatment for EGFR-mutated non-small-cell lung carcinoma (NSCLC). To date, a biomarker to predict whether NSCLC will exhibit a short- or long-term response to first- or second-generation EGFR-TKIs has not been established for clinical use. Human epidermal growth factor receptor-2 (HER2) aberrations are mechanisms for acquired resistance to EGFR-TKIs; however, their impact on EGFR-TKI therapy outcomes in EGFR-mutant NSCLC has not yet been systematically evaluated. Methods: Patients with advanced NSCLC were prospectively registered from more than 35 institutes (HER2-CS STUDY UMIN 000017003). EGFR mutations or anaplastic lymphoma kinase gene translocations were assessed at each institution using a commercially approved test. HER2 protein expression levels were determined by immunohistochemistry (IHC) using the Ventana I-VIEW PATHWAY anti-HER-2/neu (4B5). The IHC status scoring system applied to gastric cancer was used. Results: Of 1,126 screened patients with NSCLC, 354 (31.8%) had EGFR-mutated tumors, and the HER2 protein statuses were as follows: IHC0 (n = 71, 26%), IHC1+ (n = 148, 53%), IHC2+ (n = 51, 18%), and IHC3+ (n = 7, 3%). The patients’ demographics were almost identical in those with lung tumors harboring EGFR mutations and HER2-IHC2+/3+ (group P) or EGFR mutations and HER2-IHC0/1 (group N). The EGFR-TKI response rates were not different between these groups (Table). However, group P showed significantly shorter time to EGFR-TKI treatment failure than group N (median 19.1 vs. 13.3 months; log rank p = 0.038). Conclusions: These data from a large prospective cohort show that HER2 protein expression in EGFR-mutant NSCLC may have a negative impact on the effect of EGFR-TKIs. A clinical trial of EGFR/HER2-TKIs (e.g., afatinib) is warranted for this population. [Table: see text]

Activity of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients (pts) with NSCLC with uncommon EGFR mutations: A real-world cohort study (UpSwinG).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9072-9072
Author(s):  
Satoru Miura ◽  
Te-Chun Hsia ◽  
Jen-Yu Hung ◽  
Hyun Ae Jung ◽  
Jin-Yuan Shih ◽  
...  
Keyword(s):  
Real World ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Pathology Reports ◽  
Multi Center Study ◽  
Line Of Therapy ◽  
Ecog Ps ◽  
Egfr Tki ◽  
Egfr Tkis

9072 Background: EGFR TKIs are an established treatment (tx) option for pts with EGFR mutation-positive NSCLC with common mutations (Del19 or L858R); however, 7–23% of NSCLC tumors harbor uncommon EGFR mutations, where EGFR TKI efficacy is less established. These mutations are highly heterogeneous, and developments in detection by NGS are helping to identify mutations with little or no clinical data. Methods: In this non-interventional, global, multi-center study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve pts with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q or S768I], ‘other’ or compound mutations) treated with erlotinib, gefitinib, afatinib, osimertinib or other systemic therapy. Endpoints were time to tx failure (TTF), ORR, OS and duration of response (DoR). Results: Overall, 246 pts (median age: 69.5 yrs; Asian: 84%; brain metastases: 8%; ECOG PS ≥2: 16%) were recruited from 9 countries. Most pts (n=226; 92%) received an EGFR TKI as 1st-line therapy; 132 (54%), 105 (43%) and 7 (3%) received afatinib, 1st-gen TKIs and osimertinib, respectively. 57% of pts received >1 line of therapy. Most pts (73%) had a major uncommon mutation, 9% had other mutations and 33% had a compound mutation; these were detected using PCR (75%) or sequencing (25%), mainly based on tissue biopsy (86%). Pathology reports varied in quality, often lacking detail on specific mutations e.g. 21% of ex18 and 72% of ex20ins were undefined. Median TTF and OS with EGFR TKIs were 9.9 and 24.4 mos; ORR was 42%. In pts treated with 1st-line chemotherapy (n=20), median TTF and ORR were 6.6 mos and 41%. Outcomes were most favorable in major uncommon and compound mutations (Table). TTF appeared to be higher with afatinib vs 1st-gen EGFR TKIs. In most mutation categories, median OS was >2 yrs, possibly reflecting high subsequent therapy uptake. Conclusions: In a real-world setting, EGFR TKIs were the preferred tx option in pts with uncommon EGFR mutations; strongest outcomes were seen in major uncommon and compound mutations, and in pts treated with afatinib. Data were in line with recent analyses of afatinib in uncommon mutations. Tx with an EGFR TKI should be considered as standard for most pts with uncommon mutations. Optimal tx for pts with uncommon mutations requires improvements in pathology reports, with more emphasis on NGS methodology and precise definition of mutations. Clinical trial information: NCT04179890. [Table: see text]

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

scholarly journals Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1520
Author(s):  
Alessandro Leonetti ◽  
Mjriam Capula ◽  
Roberta Minari ◽  
Giulia Mazzaschi ◽  
Alessandro Gregori ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Dynamic Change ◽  
Complete Response ◽  
Dynamic Evaluation ◽  
Tki Treatment ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr Tkis

Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of EGFR-mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR-21, miR-27a and miR-181a) as a surrogate for predicting EGFR-TKI performance in EGFR-mutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFR-mutated NSCLC patients treated with EGFR-TKIs were collected at different points in time and miRNA levels were assessed by RT-PCR. Results: Higher basal values of miR-21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR-21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR-TKI treatment showed that patients who experienced SD had an increase in miR-21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miR-27a (FC = 3.1) and miR-181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR-21 levels in NSCLC cells that became resistant after exposure to EGFR-TKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR-21, and their dynamic change over time in predicting EGFR-TKI response in EGFR-mutated NSCLC.

EGFR-activating mutations and treatment with tyrosine-kinase inhibitors (TKI) to revert poor-prognosis (PP) associated with liver metastases (LM) in stage IV non-small cell lung cancer (NSCLC) patients (pts).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19106-e19106
Author(s):  
Eduardo Castanon ◽  
Maria D. Lozano ◽  
Juan Pablo Fusco ◽  
Estefania Arevalo ◽  
Omar Esteban Carranza ◽  
...  
Keyword(s):  
Survival Rate ◽  
Clinical Outcome ◽  
Kinase Inhibitors ◽  
Stage Iv ◽  
Egfr Mutations ◽  
Wild Type ◽  
Molecular Alterations ◽  
Activating Mutations ◽  
One Year ◽  
Egfr Tki

e19106 Background: LM appear in 20-30% of pts diagnosed with NSCLC and they confer PP. However, whether the clinical outcome of NSCLC pts with LM harboring molecular alterations in EGFR, KRAS and EML4-ALK genes is substantially different depending on their distinct status is still unknown. Methods: A total of 268 consecutive stage IV NSCLC pts were included. The tumor molecular analysis for EGFR, KRAS and EML4-ALK was available in 205 pts (76.5%), 136 pts (50.7%) and 31 pts (11.6%), respectively. An EGFR mutation was observed in 32 pts (15.6%), KRAS was mutated in 28 pts (20.6%) and EML4-ALK gene rearrangement was observed in 3 pts (9.6%). We aimed to determine whether the molecular status of EGFR, KRAS and EML4-ALK has an impact on the clinical outcome of stage IV NSCLC pts. Results: Most of the pts were men (71.3%). The most common histology was adenocarcinoma (59.3%). Overall, 34% of the pts showed LM at any time of the disease course. Among the whole cohort, median OS for LM pts was 16 months vs 42 months for pts with metastases other than LM (p<0.001). Among pts with LM and EGFR mutations, the one-year survival rate was 85.7% vs 54.3% for pts with LM and EGFR wild-type (p=0.03). We analyzed whether pts received EGFR TKI or standard chemotherapy (SC). For the subgroup of pts carrying EGFR mutations and receiving TKI, the 18-month survival rate was 75% for those showing LM vs 80% (p=0.44) for those without LM. In contrast, for the subgroup of EGFR wild-type pts receiving SC, the 18-month survival rate was 32.4% for those showing LM vs 74.9% for those without LM (p<0.001). No impact of KRAS or EML4-ALK molecular alterations on OS of pts with LM was observed. Conclusions: The presence of LM at any time of the disease curse negatively impacts on the clinical outcome of NSCLC pts. However, the presence of EGFR activating mutations significantly improves the OS of those with liver spread, reaching a similar OS to subjects with no LM. Pts with EGFR mutations and LM may revert the PP associated to LM when an EGFR TKI is prescribed.

scholarly journals First- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large, real-world cohort of patients with non-small cell lung cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110357
Author(s):  
Allen Chung-Cheng Huang ◽  
Chi-Hsien Huang ◽  
Jia-Shiuan Ju ◽  
Tzu-Hsuan Chiu ◽  
Pi-Hung Tung ◽  
...  
Keyword(s):  
Real World ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Rank Test ◽  
Third Generation ◽  
Log Rank Test ◽  
Epidermal Growth ◽  
Tki Treatment ◽  
Egfr Tki

Background: There are limited comparisons of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in large, real-world cohorts of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR) mutations. Methods: Patients with advanced NSCLC ( N = 612) with common EGFR mutations receiving first-line gefitinib/erlotinib and afatinib were grouped and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutations were analyzed. Results: The gefitinib/erlotinib and afatinib groups each contained 206 patients after matching. Compared with gefitinib/erlotinib, patients receiving afatinib achieved longer median PFS (16.3 versus 14.2 months; log-rank test p = 0.020) and had a lower risk of progression [hazard ratio (HR) 0.73 (95% confidence interval (CI), 0.57–0.94); p = 0.017]. Median OS (37.3 versus 34.2 months; log-rank test p = 0.500) and reduction in risk of death [HR 0.89 (95% CI, 0.65–1.23); p = 0.476] did not differ significantly between groups. T790M positivity was significantly higher in the gefitinib/erlotinib than afatinib group (70.9% versus 44.6%, p < 0.001). Multivariate analysis demonstrated that afatinib was independently associated with lower T790M positivity [odds ratio (OR) 0.27 (95% CI, 0.14–0.53); p < 0.001], whereas ⩾12 months PFS after EGFR-TKI treatment [OR 3.00 (95% CI, 1.56–5.98); p = 0.001] and brain metastasis [OR 2.12 (95% CI, 1.08–4.26); p = 0.030] were associated with higher T790M positivity. Sequential third-generation EGFR-TKI treatment was administered to 63 patients, in whom median OS after the second–third-generation and first–third-generation EGFR-TKI sequences were 38.8 and 29.1 months, respectively. Conclusion: Compared with gefitinib/erlotinib, afatinib had a higher treatment efficacy and a lower secondary T790M positivity in a large, real-world cohort of Asian patients with EGFR-mutated NSCLC.

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.

scholarly journals Mutation status and immunohistochemical correlation of EGFR mutations in gastrointestinal stromal tumors

2021 ◽  
Vol 24 (1) ◽  
pp. 67-72
Author(s):  
H Ozkayalar ◽  
MC Ergoren ◽  
G Tuncel ◽  
S Kurt ◽  
E Cevik ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Stromal Tumors ◽  
Molecular Alterations ◽  
Treatment Regimes ◽  
Research Areas ◽  
Turkish Patients

Abstract Being one of the leading causes of cancer deaths worldwide and their resistance to conventional treatment methods, made gastrointestinal stromal tumors (GISTs) one of the hot topics in medical research areas in the past decade. To investigate molecular alterations underlying the tumor is of great importance to be able to develop new, targeted treatment options. In this study, GIST samples obtained from 40 Turkish patients were analyzed for actionable epidermal growth factor receptor (EGFR) mutations that are related to treatment regimes in non small cell lung cancer (NSCLC) to understand whether EGFR expression is altered in GISTs. Established alterations in EGFR can make the use of tyrosine kinase inhibitors possible, which are currently used in cancer therapy, especially in NSCLC. Our results indicated that EGFR mutations are rare in GISTs. Further research is needed to sequence whole coding regions of the gene to investigate new actionable mutations in EGFR in an increased sample size.

Response with pemrbolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R

2021 ◽  
pp. 107815522110578
Author(s):  
Matthew J. Hadfield ◽  
Alla Turshudzhyan ◽  
Khalid Shalaby ◽  
Aswanth Reddy
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Durable Response ◽  
Egfr Mutated

Introduction Lung cancer is the leading cause of cancer-related deaths with non-small cell lung cancer (NSCLC) being the most common of them. About a third of NSCLC cases have an epidermal growth factor (EGFR) mutation, which is usually susceptible to tyrosine kinase inhibitors (TKIs). In rare cases where patients progress through TKI therapy, the use of immune checkpoint inhibitors (ICIs) remains controversial. Case report We describe a case of a patient with significant history of smoking and EGFR mutated programmed death ligand-1 (PD-L1) positive NSCLC who was initially treated with TKI therapy. Management/Outcome While patient progressed on TKI therapy, he was able to achieve a durable response with a single PD-L1 agent, pembrolizumab. Contrary to the available evidence, the presented EGFR mutant NSCLC responded to PD-L1 pathway inhibition. Discussion From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.

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