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 Vasculogenic mimicry, a negative indicator for progression free survival of lung adenocarcinoma irrespective of first line treatment and epithelial growth factor receptor mutation status

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejun He ◽  
Jijun You ◽  
Haibing Ding ◽  
Zhisheng Zhang ◽  
Lin Cui ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Target Therapy ◽  
Vasculogenic Mimicry ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Abstract Background Vascular mimicry (VM) was associated with the prognosis of cancers. The aim of the study was to explore the association between VM and anticancer therapy response in patients with lung adenocarcinoma. Methods This was a single-center retrospective study of patients with lung adenocarcinoma between March 1st, 2013, to April 1st, 2019, at the Second People’s Hospital of Taizhou City. All included patients were divided into the VM and no-VM groups according to whether VM was observed or not in the specimen. Vessels with positive PAS and negative CD34 staining were confirmed as VM. The main outcome was progression-free survival (PFS). Results Sixty-six (50.4%) patients were male. Eighty-one patients received chemotherapy as the first-line treatment, and 50 patients received TKIs. Forty-five (34.4%) patients were confirmed with VM. There was no difference regarding the first-line treatment between the VM and no-VM groups (P = 0.285). The 86 patients without VM had a median PFS of 279 (range, 90–1095) days, and 45 patients with VM had a median PFS of 167 (range, 90–369) days (P < 0.001). T stage (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.10–1.71), N stage (HR = 1.43, 95%CI: 1.09–1.86), M stage (HR = 2.85, 95%CI: 1.76–4.61), differentiation (HR = 1.85, 95%CI: 1.29–2.65), therapy (HR = 0.32, 95%CI: 0.21–0.49), VM (HR = 2.12, 95%CI: 1.33–3.37), and ECOG (HR = 1.41, 95%CI: 1.09–1.84) were independently associated with PFS. Conclusion The benefits of first-line TKIs for NSCLC with EGFR mutation are possibly better than those of platinum-based regimens in patients without VM, but there is no difference in the benefit of chemotherapy or target therapy for VM-positive NSCLC harboring EGFR mutations.

scholarly journals Efficacy of First-Third generation EGFR inhibitor combined with chemotherapy as first-line treatment for advanced lung adenocarcinoma in a real-world setting

2021 ◽  
Author(s):  
Ming-Wei Chen Ming-Wei Chen ◽  
An-Tai He . ◽  
Yi Pei .
Keyword(s):  
Lung Adenocarcinoma ◽  
Survival Time ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Combination Group ◽  
First Line ◽  
Free Survival ◽  
Mean Survival Time ◽  
First Line Therapy ◽  
To Receive

Abstract BackgroundTo explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head-to-head study was performed to compare chemotherapy and gefitinib-erlotinip, osimertinib treatment in combination or with either agent alone as first-line therapy, in terms of efficacy and safety.MethodsA total of 200 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib-erlotinip combined with pemetrexed and carboplatin group, gefitinib-erlotinip osimertinib combined with pemetrexed and carboplatin group, pemetrexed plus carboplatin alone group, or gefitinib-erlotinip alone group, osimertinib alone group.ResultsThe progression-free survival (PFS) of patients in the gefitinib-erlotinip combination group Mean Survival Time PFS 22.00 month,95%CI[16.29,27.70] and osimertinib gefitinib-erlotinip combination group Mean Survival Time PFS 40.00 month,95%CI[28.12,51.87]was longer than that of patients in the chemotherapy alone group PFS10,81 months, 95% CI,[ 8.99–12.64],gefitinib-erlotinip alone group PFS14.00 month.95%CI[11.98-20.01], osimertinib alone group PFS 26.66 month 95%CI[24.77-29.22].The gefitinib-erlotinip osimertinib combinational resulted in longer overall survival (OS) than chemotherapy alone (HR = 0.46, p = 0.016) or gefitinib-erlotinip alone (HR = 0.36, p = 0.01). osimertinib alone (HR = 0.26, p = 0.01).ConclusionsOur finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib-erlotinip and pemetrexed plus carboplatin combined with gefitinib-erlotinip osimertinib group could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.

scholarly journals Complete Response to Afatinib of an EGFR Exon 18 delE709_T710insD-Mutated Stage IV Lung Adenocarcinoma

2021 ◽  
Author(s):  
Blandine Jelli ◽  
Olivier Taton ◽  
Nicky D'Haene ◽  
Myriam Remmelink ◽  
Zita Mekinda
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Complete Response ◽  
Egfr Mutations ◽  
First Case ◽  
Treatment Interruptions ◽  
Patient Prognosis ◽  
Lung Adenocarcinomas

Introduction: Epidermal growth factor receptor (EGFR) mutations are frequently found in patients with lung adenocarcinomas, 90% being deletions in exon 19 or point mutation in exon 21. Three generations of tyrosine kinase inhibitors (TKIs) targeting EGFR mutations are available and have changed patient prognosis but less data is available on exon 18 mutations and their sensitivity to TKI therapy. Exon 18 delE709_T710insD accounts for 0.06% (16/27,294) of all EGFR mutations and is an oncogenic driver. Several partial responses to afatinib have been described. Case description: We report the first case, to the best of our knowledge, of the complete response to afatinib of a 57-year-old patient with stage IV lung adenocarcinoma with a delE709_T710insD mutation in the EGFR gene detected by next-generation sequencing. Oral afatinib was prescribed and despite treatment interruptions and dosage tapering due to cutaneous adverse events, a complete response was achieved 12 months after treatment initiation and is currently maintained at 17 months. Conclusion: When EGFR mutation is suspected, complete DNA sequencing of exons 18 to 21 should be carried out and we suggest that afatinib should be the first-line treatment for exon 18 delE709_T710insD-mutated advanced lung adenocarcinomas.

scholarly journals Neoadjuvant EGFR-TKI Therapy for EGFR-Mutant NSCLC in Traditionally Unresectable Patients

2021 ◽  
Author(s):  
Ke-Cheng Chen ◽  
Shuenn-Wen Kuo ◽  
Chen-Hao Hsiao ◽  
Jing-Shing Chen
Keyword(s):  
Thoracic Surgery ◽  
Lung Adenocarcinoma ◽  
Surgical Resection ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Multidisciplinary Management ◽  
Advanced Stage ◽  
Nsclc Patients

Abstract IntroductionAdvanced stage non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations may have benefit from tyrosine kinase inhibitors (TKI). However, the role of multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery is uncertain. This study assessed the possible impact of neoadjuvant TKI therapy and thoracic surgery in selected advanced stage patients.MethodsAdvanced stage of IIIB and IVA NSCLC patients were retrospectively reviewed from 2010 to 2013. Patients with EGFR mutations who received neoadjuvant TKI followed by surgical resection were included. All patients were followed up for 5 years or until death.ResultsThere were total 15 advanced stage lung adenocarcinoma patients in the study. 8 patients were stage IIIB and 7 were stage IVA. All tumor sizes significantly decreased after neoadjuvant TKI therapy (p value = 0.0002). 11 patients received adjuvant TKI therapy after surgical resection and others received adjuvant cisplatin-based chemotherapy. Progression-free survival was superior in the group of adjuvant TKI therapy than in the group of adjuvant chemotherapy (median 14 months versus 5.9 months, p value = 0.016). Overall survival (OS) was not different between two groups (p value = 0.755). In the group of adjuvant TKI therapy, median OS in patients harboring exon 19 deletion and exon 21 L858R was 60 months and 44.9 months, respectively (p value = 0.078). ConclusionTKI may decrease the size of EGFR mutation lung adenocarcinoma. A multidisciplinary management including neoadjuvant TKI therapy and thoracic surgery may be discussed in selected advanced stage lung adenocarcinoma.

Clinical Efficacy of Afatinib Treatment for a Patient with Leptomeningeal Carcinomatosis

Chemotherapy ◽  
2016 ◽  
Vol 62 (3) ◽  
pp. 147-150 ◽  
Author(s):  
Yo Kawaguchi ◽  
Jun Hanaoka ◽  
Hideki Hayashi ◽  
Naoki Mizusaki ◽  
Hirotoshi Iihara ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Leptomeningeal Carcinomatosis ◽  
Leptomeningeal Metastases ◽  
Egfr Tyrosine Kinase Inhibitor ◽  
Free Survival ◽  
Epidermal Growth ◽  
Egfr Mutated

Leptomeningeal metastases occur in 1% of patients with non-small-cell lung cancer. There have been several reports on the treatment of leptomeningeal metastases with afatinib. Our patient was a 41-year-old woman who had never smoked and was diagnosed with stage IV adenocarcinoma of the lung with an epidermal growth factor receptor (EGFR) mutation. She was treated with afatinib for the recurrence of leptomeningeal metastases. After the treatment with afatinib was initiated, the neurological symptoms dramatically regressed, and she achieved progression-free survival for 7 months. The concentration of afatinib in the cerebrospinal fluid (CSF) ranged from 0.05 to 0.14 ng/mL, and the penetration rate of afatinib from the plasma to the CSF ranged from 0.28 to 0.40%. This concentration might be sufficient to achieve a clinical effect for leptomeningeal carcinomatosis. Therefore, afatinib administered at the usual doses may be an effective treatment for leptomeningeal carcinomatosis of EGFR-mutated or EGFR-tyrosine kinase inhibitor-sensitive lung adenocarcinoma.

scholarly journals The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation

2020 ◽  
Vol 12 ◽  
pp. 175883592094615
Author(s):  
Shang-Gin Wu ◽  
Chong-Jen Yu ◽  
James Chih-Hsin Yang ◽  
Jin-Yuan Shih
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Tissue Samples ◽  
Epidermal Growth ◽  
Egfr Tkis ◽  
First Line Treatment

Background and aims: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are effective against classical EGFR mutations in lung cancer. However, their effectiveness and the prognosis of lung cancer patients with complex EGFR mutations are not well delineated. Therefore, we aimed to investigate the treatment effectiveness of different EGFR TKIs in patients with complex EGFR mutations. Patients and methods: From 2005 to 2020, we collected lung adenocarcinoma tissue samples for EGFR mutation analysis using direct Sanger sequencing. Patients with EGFR mutations treated with EGFR TKIs as first-line treatment were enrolled. Clinical characteristics, EGFR mutation status, treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Among 2675 patients with EGFR mutations, 239 (8.9%) had complex EGFR mutations, of whom 125 received EGFR TKI treatment as first-line treatment. Multivariate analysis revealed that afatinib was a more favorable factor for PFS than gefitinib [hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.11–3.62] and erlotinib (HR, 2.61; 95% CI, 1.31–5.22), especially in patients with uncommon mutation patterns. Afatinib treatment as first-line treatment was also associated with longer OS compared with erlotinib (HR, 2.48; 95% CI, 1.20–5.12). Classical mutation pattern was associated with longer PFS ( p = 0.001) and OS ( p = 0.020). Secondary T790M was detected in 22 of 52 (42.3%) patients who had re-biopsied tissue samples after acquiring resistance to EGFR TKIs. There was no significant difference in secondary T790M formation after acquired resistance to the three EGFR TKIs ( p = 0.261). Furthermore, three (5.8%) patients had small-cell lung cancer transformation. Conclusion: Afatinib is an effective first-line treatment for patients with lung adenocarcinoma harboring complex EGFR mutations, especially those with uncommon mutation patterns.

scholarly journals Impact of epidermal growth factor receptor gene expression level on clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients taking first-line epidermal growth factor receptor–tyrosine kinase inhibitors

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769593 ◽  
Author(s):  
Huang-Chih Chang ◽  
Yu-Mu Chen ◽  
Chia-Cheng Tseng ◽  
Kuo-Tung Huang ◽  
Chin-Chou Wang ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Free Survival ◽  
Lung Cancer Patients ◽  
Epidermal Growth ◽  
Egfr Mutant

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are first-choice treatments for advanced non-small-cell lung cancer patients harboring EGFR mutations. Although EGFR mutations are strongly predictive of patients’ outcomes and their response to treatment with EGFR-TKIs, early failure of first-line therapy with EGFR-TKIs in patients with EGFR mutations is not rare. Besides several clinical factors influencing EGFR-TKI efficacies studied earlier such as the Eastern Cooperative Oncology Group performance status or uncommon mutation, we would like to see whether semi-quantify EGFR mutation gene expression calculated by 2−ΔΔct was a prognostic factor in EGFR-mutant non-small cell lung cancer patients receiving first-line EGFR-TKIs. This retrospective study reviews 926 lung cancer patients diagnosed from January 2011 to October 2013 at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. Of 224 EGFR-mutant adenocarcinoma patients, 148 patients who had 2−ΔΔct data were included. The best cutoff values of 2−ΔΔct for in-frame deletions in exon 19 (19 deletion) and a position 858 substituted from leucine (L) to an arginine (R) in exon 21 (L858R) were determined using receiver operating characteristic curves. Patients were divided into high and low 2−ΔΔct expression based on the above cutoff level. The best cutoff point of 2−ΔΔct value of 19 deletion and L858R was 31.1 and 104.7, respectively. In all, 92 (62.1%) patients showed high 2−ΔΔct expression and 56 patients (37.9%) low 2−ΔΔct expression. The mean age was 65.6 years. Progression-free survival of 19 deletion mutant patients with low versus high expression level was 17.07 versus 12.04 months (P = 0.004), respectively. Progression-free survival of L858 mutant patients was 13.75 and 7.96 months (P = 0.008), respectively. EGFR-mutant lung adenocarcinoma patients with lower EGFR gene expression had longer progression-free survival duration without interfering overall survival.

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