EGFR gene mutation is not a significant prognostic factor in patients with EGFR mutated non-small cell lung cancer who receive best supportive care alone.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21736-e21736
Author(s):  
Takeshi Masuda ◽  
Yu Wakabayashi ◽  
Kiyofumi Shimoji ◽  
Kakuhiro Yamaguchi ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Supportive Care ◽  
Egfr Mutation ◽  
Best Supportive Care ◽  
Small Cell ◽  
Significant Prognostic Factor ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki

e21736 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), are less toxic than conventional chemotherapy drugs, and benefit patients with EGFR-mutated non-small cell lung (NSCLC) cancer. However, there are a few patients who are not able to receive EGFR-TKI due to poor performance status, older age, or sever comorbidities. Here, we aimed to determine the prognostic significance of EGFR mutation in NSCLC patients who received best supportive care (BSC) alone, and compare the anti-tumor outcomes of only EGFR-TKI-treated patients vs. BSC patients. Methods: We retrospectively reviewed the medical records of patients diagnosed with NSCLC at Higashihiroshima Medical Center during April 1991–January 2019 and Hiroshima University Hospital during April 2008–August 2018. Results: A total of 1163 patients diagnosed with unresectable NSCLC were included in this analysis. Of these 1163 patients, 234 patients received BSC alone.Among 196 patients who underwent EGFR mutation analysis, 38 and 158 did and did not harbor an EGFR mutation, respectively, and the mean survival times (MST) did not differ significantly between these groups (121 vs. 85 days, p = 0.789). Consistent with the survival analysis, the multivariate Cox regression analyses showed EGFR mutation was not an independent prognostic factor. After propensity score matching, a comparison of only EGFR-TKI-treated (n = 35) and BSC patients (n = 35) with EGFR mutation revealed that the former had a significantly longer MST than the latter (372 vs. 121, p < 0.001). Conclusions: EGFR mutation itself was not a significant prognostic factor in untreated NSCLC patients. The patients who received EGFR-TKI had a significantly longer MST than their untreated counterparts. Our results may help to explain the benefit of EGFR-TKI, particularly for patients who would be directed towards treatment with BSC.

scholarly journals Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

Exon-16-skipping ERBB2 (ERBB2ΔEx16) as a novel resistance mechanism against EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9528-9528
Author(s):  
Xin Zhao ◽  
Linling Jin ◽  
Man Yu ◽  
Qiuxiang Ou ◽  
Hua Bao ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Small Cell ◽  
Large Fragment ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr T790m ◽  
Erbb2 Amplification

9528 Background: In addition to ERBB2 amplification/protein overexpression, activating ERBB2 alterations have been increasingly discovered in diverse human cancers with varying incidence. ERBB2ΔEx16 is an alternatively spliced isoform of ERBB2, lacking the entire exon 16 which encodes a small extracellular domain. ERBB2ΔEx16 was recently reported to lead to oncogenic activation of ERBB2 and osimertinib resistance in EGFR T790M+ non-small cell lung cancer (NSCLC). Methods: A total of 38,680 Chinese cancer patients whose tumor specimen or circulating cell-free DNA underwent genomic profiling by targeted next-generation sequencing of cancer-related genes were retrospectively reviewed. Clinicopathological features and treatment history of ERBB2ΔEx16+ patients were evaluated. RNA sequencing was performed to validate the presence of exon-16-skipping ERBB2 at the transcriptional level. Results: A total of eighteen ERBB2ΔEx16+ patients (11 NSCLC, 2 colorectal cancer, 2 gastric cancer, and 3 others) were identified (0.047%, 18/38,680). ERBB2 exon 16 skipping may result from large fragment deletion spanning the whole or partial region of exon 16 (72.2%, 13/18), base substitution at the splice acceptor site (16.7%, 3/18) and deletion of the splice donor site (11.1%, 2/18). ERBB2 exon 16 skipping, including large fragment deletion and splice site deletion, was validated at the RNA level by RNA sequencing in 3 patients with available samples. Co-occurrence of ERBB2 amplification and ERBB2 mutations were found in 83.3% (15/18) and 50% (9/18) of cases, respectively. Concurrent copy number variations were prevalent in CDK12 (55.6%, 10/18), CDKN2B (44.4%, 8/18), NKX2.1 (38.9%, 7/18) and PTPRD (33.3%, 6/18). Among the 11 cases of ERBB2ΔEx16+ NSCLC, 9 had coexisting activating EGFR mutations (exon 19 deletions, exon 21 L858R) and received prior treatment with EGFR tyrosine kinase inhibitors (TKIs), with 2 harboring acquired EGFR T790M mutation and 1 EGFR copy number gain. Further analysis of the matched pretreatment samples in 3 EGFR-mutated NSCLC patients confirmed that ERBB2ΔEx16 was acquired during EGFR TKI therapy. In the 7 cases of other cancers, 4 to 31 non- ERBB2 mutations were identified in each sample, with TP53 being the most frequently mutated gene. Conclusions: Our data suggest that ERBB2ΔEx16 may be a general mechanism of EGFR TKI resistance in a subset of EGFR-mutated NSCLC patients, in addition to being an oncogenic driver as reported in some solid malignancies including colorectal, gastric and ovarian cancers.

scholarly journals Prognostic factor of patients with advanced non-small cell lung cancer receiving best supportive care

2017 ◽  
Vol 28 ◽  
pp. ix110
Author(s):  
Takayuki Kishikawa ◽  
Shingo Masuda ◽  
Shinya Oda ◽  
Keisuke Yamaguchi ◽  
Yuichiro Furusato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Supportive Care ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Best Supportive Care ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Patterns and Treatment Strategies of Osimertinib Resistance in T790M-Positive Non-Small Cell Lung Cancer: A Pooled Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunsheng Wang ◽  
Kewei Zhao ◽  
Shanliang Hu ◽  
Minghuan Li ◽  
Yipeng Song
Keyword(s):  
Lung Cancer ◽  
Clinical Characteristics ◽  
Egfr Mutation ◽  
Treatment Strategies ◽  
Pooled Analysis ◽  
Small Cell ◽  
Resistance Pattern ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tki

IntroductionOsimertinib resistance is inevitable. The purpose of this study was to explore the predictive value of pretreatment clinical characteristics in T790M-positive non-small cell lung cancer NSCLC patients for the resistance pattern of osimertinib during tumor progression as well as the treatment strategy.MethodsWe performed a literature search in the NCBI PubMed database to identify relevant articles and completed a pooled analysis based on 29 related published studies. The relationship between clinical characteristics, EGFR mutation type, previous treatment history and the gene mutation pattern at resistance to osimertinib was analyzed.ResultsA total of 38 patients were included in the pooled analysis. Patients with an initial epidermal growth factor receptor EGFR mutation status of 19 deletions were more likely to have T790M loss (HR: 12.187, 95% CI: 2.186–67.945, p = 0.004). Patients with an initial EGFR mutation of L858R were more likely to have C797S mutations (HR: 0.063, 95% CI: 0.011–0.377, p = 0.002). The other factors (age, gender, ethnicity, smoking history, previous EGFR-TKI targeted therapy history, history of radiotherapy and chemotherapy) were not associated with the resistance pattern of osimertinib (all p &gt; 0.05).ConclusionsThe type of EFGR mutation in T790M-positive NSCLC patients prior to treatment can predict the resistance pattern to osimertinib. This finding plays a vital role and theoretical basis in guiding clinicians to formulate treatment strategies at the early stage of treatment and rationally combine drugs to overcome EGFR-TKI resistance.

Elevated serum level of sialylated glycoprotein KL-6 predicts a poor prognosis in patients with non-small cell lung cancer treated with gefitinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18162-18162
Author(s):  
Y. Fujiwara ◽  
K. Kiura ◽  
S. Toyooka ◽  
K. Hotta ◽  
M. Tabata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
High Serum ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Nsclc Patients

18162 Background: The Factors affecting survival after gefitinib treatment in patients with non-small cell lung cancer (NSCLC) remain to be fully elucidated, although epidermal growth factor receptor (EGFR) mutation is a substantial prognostic factor. KL-6 has been studied as a useful indicator for interstitial lung diseases, however, it was first discovered as a pulmonary adenocarcinoma-related antigen. The aim of this study was to investigate the prognostic value of the serum KL-6 levels in advanced NSCLC patients treated with gefitinib and thus determine its association with the EGFR mutation status. Methods: Between September 2002 and September 2005, 41 patients with NSCLC were treated with gefitinib after having their serum KL-6 levels measured at Okayama University Hospital. EGFR mutations were analyzed by direct sequence methods. Results: The serum KL-6 levels ranged from 199 to 9080 U/ml (median, 550 U/ml), and 54% of 41 patients showed a level higher than the cut-off level of 500 U/ml. The median progression-free survival (PFS) time and the median overall survival (OS) time were 4.7 months and 13.9 months, respectively. Multivariate analyses revealed that the elevated KL-6 level was an independent adverse prognostic factor for PFS (hazard ratio: 2.278, p = 0.040) as well as OS (hazard ratio: 4.858, p = 0.002) in NSCLC patients treated with gefitinib. The EGFR mutation status was analyzed in 22 patients (54%). Among those with wild-type EGFR, the patients with high serum KL-6 levels also had a worse survival than those within normal serum KL-6 levels (6.5 months versus 13.3 months, p = 0.0194). Conclusions: Our data suggest that NSCLC patients with high serum KL-6 levels tended to have a poor clinical outcome when treated with gefitinib. No significant financial relationships to disclose.

scholarly journals Efficacy and acquired resistance of EGFR-TKI combined with chemotherapy as first-line treatment for Chinese patients with advanced non-small cell lung cancer in a real-world setting

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting. Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity. Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.67–23.33] vs. 11.70 months [95% CI, 10.81–12.59], p < 0.001). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.30–41.70) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

Effectiveness of osimertinib plus chemotherapy and avastin for untreated EGFR-mutated advanced non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21178-e21178
Author(s):  
Fang Wang ◽  
Hui Liu ◽  
Zhen Zeng ◽  
Shasha Wang ◽  
Haifeng Qin
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Mutated

e21178 Background: Osimertinib is recommended as a novel first-line standard treatment for advanced Non-Small-Cell Lung Cancer (NSCLC) patients with EGFR mutation. However, there are also patients with concurrent mutation or/and metastases have limited benefits. According to the current remission rate, regression depth and PFS data, the main mechanism of the benefit of combined anti-angiogenesis or chemotherapy is to reduce tumor load and heterogeneous reserve to a greater extent, so as to extend the remission time, that is, to delay the occurrence of drug resistance to extend PFS. This prospective study aims to investigate the efficacy and safety of Osimertinib plus chemotherapy and Avastin for Untreated EGFR-Mutated advanced NSCLC. Methods: The study enrolled 22 patients diagnosed with untreated advanced NSCLC and tested with EGFR mutation, who received osimertinib ( 80mg QD) plus pemetrexed (500mg/m2), cisplatin (75mg/m2) and bevacizumab (7.5mg/kg) for 6 cycles, then maintained with osimertinib/pemetrexed/bevacizumab. The primary endpoint was progression free survival (PFS). The secondary endpoint was objective response rate (ORR). Treatment was continued until disease progression and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The toxicity was determined according to CTCAE 4.0. Results: From February, 2018 to July, 2020, 22 patients enrolled. All the patients were evaluated and showed partial response(PR) when make efficacy evaluation at the first time. The target lesions reduction were shown. The average reduction is 48%, ranged from 32% of Pt12 to 71% of Pt11. Up to January, 2021, all the patients are still under the treatment. Especially for Pt7 who has already benefited from the treatment protocol by 35months. The toxicities associated with this protocols were manageable. Only 1 patient was 3/4-grade Anemia, 1 patient was 3/4-grade Diarrhea and 3 patients was 3/4-grade Lymphopenia. Conclusions: Osimertinib in combination with chemotherapy and Bevacizumab. exhibits superior activity and generally manageable toxicities for the naive advanced NSCLC patients with EGFR mutant, especially for the patients with concurrent mutation or/and metastases. It may provide a new and effective therapy strategy for them, but large sample and additional clinical trials are also needed.

scholarly journals A phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected non-small-cell lung cancer with EGFR mutation (West Japan Oncology Group 11719L/ADJUST study)

2021 ◽  
Vol 13 ◽  
pp. 175883592098764
Author(s):  
Ryota Shibaki ◽  
Hiroaki Akamatsu ◽  
Terufumi Kato ◽  
Kazumi Nishino ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Egfr Mutation ◽  
Phase Ii Study ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Egfr Mutated ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is a standard treatment in EGFR-mutated advanced non-small-cell lung cancer (NSCLC); however, previous data have suggested that EGFR-TKI has limited potential as adjuvant therapy. On the contrary, based on subset analysis with the immune checkpoint inhibitor (ICI) plus platinum-doublet chemotherapy in advanced NSCLC with EGFR mutation, we hypothesized that this combination was worth testing as adjuvant therapy in patients with EGFR-mutated NSCLC. Methods: Herein, we introduce our phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected NSCLC with EGFR mutation. Accrued patients will be pathological stage II–IIIA with completely resected NSCLC and whose tumors have EGFR mutation. Treatment comprises four cycles of cisplatin plus vinorelbine combined with atezolizumab followed by maintenance with atezolizumab. The primary endpoint is the disease-free survival (DFS) rate at 2 years. Secondary endpoints are DFS, overall survival, and safety. In total, 18 patients will be enrolled in this study. Discussion: Ongoing phase III trials of adjuvant ICI allow the inclusion of patients with EGFR mutation, but our current trial will provide the earliest clinical data on the efficacy of platinum-doublet chemotherapy with atezolizumab.

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