scholarly journals Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: Are They Different from Those with Common EGFR Mutations?

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 326
Author(s):  
Hyun Ae Jung ◽  
Sehhoon Park ◽  
Jong-Mu Sun ◽  
Se-Hoon Lee ◽  
Jin Seok Ahn ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Response Rate ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Compound Mutation ◽  
Egfr Tki ◽  
Egfr Tkis

Approximately 10% of the epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are uncommon EGFR mutations. Although the efficacy of second (2G) or third generation (3G) EGFR tyrosine kinase inhibitors (EGFR-TKIs) in the patients with uncommon EGFR mutation has been proven, further studies are warranted to define the optimal treatment approach for uncommon EGFR mutation-positive NSCLC. This study retrospectively investigated the treatment patterns and outcomes of patients with uncommon EGFR mutation-positive NSCLC from January 2011 to December 2019 at the Samsung Medical Center, Seoul, Korea. During the study, 2121 patients with EGFR mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy. Of this, 135 (6.4%) patients harbored uncommon EGFR mutations. Of 135, 54 (40%, 54/135) patients had overlapping mutations with major EGFR mutations. The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8–13.5), 11.7 months (95% CI: 6.6–16.7), 7.7 months (95% CI: 4.9–17.4), and 5.0 months (95% CI: 3.7–6.1) for major uncommon EGFR mutation (G719X, L861Q), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The median overall survivals (OSs) were 25.6 months (16.9–34.2), 28.8 (95% CI: 24.4–33.4), 13.5 months (95% CI: 7.4–27.8), and 9.4 months (95% CI: 3.4–10.5) for major uncommon EGFR mutation (G719X), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The response rate, median PFS, and OS were 63.3%, 16.3 months (95% CI: 15.6–16.9), and 37.5 months (95% CI: 35.4–39.6) for common EGFR mutation-positive NSCLC. After failing 1L EGFR-TKI, repeated tissue or liquid biopsy were carried out on 44.9% (35/78) of patients with T790M detected in 10/35 (28.6%) patients. With subsequent 3G EGFR-TKI after failing the first-line EGFR-TKI, the ORR and PFS for 3G EGFR-TKI were 80% and 8.9 months (95% CI: 8.0–9.8). These patients showed a median OS of 34.6 months (95% CI: 29.8–39.4). The ORR, PFS and OS were poorer in patients with uncommon (especially other compound and other uncommon mutation) than those with common EGFR mutations. T790M was detected in 28.6% of the uncommon EGFR mutation-positive patients for whom prior 1G/2G EGFR-TKIs failed and underwent repeat biopsy at the time of progression.

A practical decision-making strategy based on clinical triple features for EGFR-TKIs to treat advanced non-small cell lung cancer patients with unknown EGFR mutation status.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19082-e19082
Author(s):  
Di Zheng ◽  
Jiying Wang ◽  
Bing Lu
Keyword(s):  
Lung Cancer ◽  
Salvage Therapy ◽  
Egfr Mutation ◽  
Response Rate ◽  
Small Cell ◽  
Smoking History ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Egfr Tki ◽  
Egfr Tkis

e19082 Background: EGFR mutated lung cancers are strongly associated with clinical characteristics of never- smoking history and adenocarcinoma histology type, and tended to develop multiple pulmonary metastases.Whether multiple pulmonary metastatic lung adenocarcinomas with never-smoking history would respond to EGFR-TKIs as those harboring EGFR active mutation remains unclear. Methods: 223 consecutive metastatic non-small cell lung cancer (NSCLC) patients with unknown EGFR status who received EGFR-TKIs as salvage therapy after failure of previous platinum-based chemotherapy in Shanghai Pulmonary hospital between 2009 and 2011 were included to the study. Available CT scans, routinely performed at baseline and one month after the start of EGFR-TKIs therapy, were reviewed independently by two investigators. For the purposes of this study, diffuse pulmonary metastatic nodules were defined as multiple nodules distributed diffusely throughout the whole lung with at least 20 nodules within the unilateral lung field. Paraffin embedded tissues were available for 45 of 223 patients for EGFR gene mutation test. Results: Of 134 never-smokers with lung adenocarcinoma,70 patients responded to EGFR-TKIs with an objective response rate (ORR) of 52.2% (70/134), and the ORR for the 62 patients with diffuse pulmonary metastatic nodules was 79% (49/62). Among the 20 patients with confirmed EGFR mutation (based on the available 45 archived specimen), the ORR was 75% (15/20). The multivariate analyses showed that the presence of diffused multiple pulmonary metastatic nodules, activating EGFR mutation and female are independent predictive factors of the response to EGFR-TKIs. Conclusions: Patient selection based on specific clinical features to recieve EGFR-TKI treatment yield high response rate comparable to that selected by EGFR mutation status. It is practical to consider EGFR-TKI as salvage therapy in non-smoking patients with lung adenocarcinoma characterized by diffuse pulmonary nodules when EGFR mutation testing is a challenge.

First-Line Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer Harboring SomaticEGFRMutations

2008 ◽  
Vol 26 (15) ◽  
pp. 2442-2449 ◽  
Author(s):  
Lecia V. Sequist ◽  
Renato G. Martins ◽  
David Spigel ◽  
Steven M. Grunberg ◽  
Alexander Spira ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Tki Resistance ◽  
Grade 3

PurposeSomatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non–small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms.Patients and MethodsChemotherapy-naïve patients with advanced NSCLC with ≥ 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. The primary outcome was response rate.ResultsNinety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification.ConclusionFirst-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care.

scholarly journals Concurrent Genetic Alterations and Other Biomarkers Predict Treatment Efficacy of EGFR-TKIs in EGFR-Mutant Non-Small Cell Lung Cancer: A Review

2020 ◽  
Vol 10 ◽  
Author(s):  
Yijia Guo ◽  
Jun Song ◽  
Yanru Wang ◽  
Letian Huang ◽  
Li Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Treatment Efficacy ◽  
Genetic Alterations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Egfr Tkis ◽  
Gene Alterations

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) greatly improve the survival and quality of life of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, many patients exhibit de novo or primary/early resistance. In addition, patients who initially respond to EGFR-TKIs exhibit marked diversity in clinical outcomes. With the development of comprehensive genomic profiling, various mutations and concurrent (i.e., coexisting) genetic alterations have been discovered. Many studies have revealed that concurrent genetic alterations play an important role in the response and resistance of EGFR-mutant NSCLC to EGFR-TKIs. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on EGFR-TKI treatment efficacy is necessary. Further exploration of other biomarkers that can predict EGFR-TKI efficacy will help clinicians identify patients who may not respond to TKIs and allow them to choose appropriate treatment strategies. Here, we review the literature on specific gene alterations that coexist with EGFR mutations, including common alterations (intra-EGFR [on target] co-mutation, TP53, PIK3CA, and PTEN) and driver gene alterations (ALK, KRAS, ROS1, and MET). We also summarize data for other biomarkers (e.g., PD-L1 expression and BIM polymorphisms) associated with EGFR-TKI efficacy.

scholarly journals Rational Application of First-Line EGFR-TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jie-Tao Ma ◽  
Yi-Jia Guo ◽  
Jun Song ◽  
Li Sun ◽  
Shu-Ling Zhang ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Formula Group ◽  
Exon 19 Deletion ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Egfr Tkis

Purpose. A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors ( A + T ) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Methods. PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs). Results. Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone ( HR = 0.60 ; P < 0.01 ) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups ( HR = 0.933 ; P = 0.551 ) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups ( RR = 0.774 ; P = 0.008 ). There was no difference in the positive rates of acquired T790M mutation between the two groups ( RR = 0.967 ; P = 0.846 ). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group ( RR = 0.881 ; P = 0.002 ). Conclusion. Addition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.

scholarly journals Optimal sequencing strategies in the treatment of EGFR mutation–positive non–small cell lung cancer: Clinical benefits and cost-effectiveness

2020 ◽  
Vol 77 (18) ◽  
pp. 1466-1476
Author(s):  
Vera Hirsh ◽  
Jaspal Singh
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
First Generation ◽  
Egfr Mutation ◽  
Cost Effective ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Optimal Sequencing ◽  
Egfr Tkis

Abstract Purpose To summarize current understanding of the efficacy, role, and cost-effectiveness of the available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and to evaluate sequencing strategies based on the available evidence. Summary. EGFR TKIs are the current standard of care for patients with EGFR mutation–positive non–small cell lung cancer (NSCLC). Five EGFR TKIs are currently approved in the United States for use in a first-line setting; these TKIs differ in mechanism of action, efficacy, safety, and cost. Most patients develop resistance to first-line EGFR TKIs and require subsequent therapy with additional EGFR TKIs, chemotherapy, and/or other targeted agents. A major consideration when selecting EGFR TKIs, both as first-line or subsequent treatment options, is cost-effectiveness. Although clinical trials have shown that the second- and third-generation EGFR TKIs are superior in efficacy to the first-generation agents, pharmacoeconomic studies suggest that the first-generation agents are the most cost-effective, with the second-generation TKI afatinib also considered cost-effective in some studies. Despite its impressive efficacy, osimertinib appears to be less cost-effective due to substantially higher acquisition costs. Conclusion Preliminary data suggest that first-line afatinib followed by osimertinib may offer promising survival outcomes and, on the basis of efficacy alone, may represent an optimal sequencing strategy in the majority of patients with EGFR mutation–positive NSCLC, in particular Asian patients and those with Del19-positive tumors. However, considerably more research into outcomes and costs associated with consecutive sequencing of EGFR TKIs is needed before any conclusions can be reached.

scholarly journals Effectiveness and Safety of EGFR-TKI Rechallenge Treatment in Elderly Patients with Advanced Non-Small-Cell Lung Cancer Harboring Drug-Sensitive EGFR Mutations

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 929
Author(s):  
Yutaka Yamada ◽  
Hisao Imai ◽  
Tomohide Sugiyama ◽  
Hiroyuki Minemura ◽  
Kenya Kanazawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Elderly Patients ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Tki Treatment ◽  
Egfr Tki

Background and Objectives: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are effective first-line chemotherapeutic agents for patients with advanced non-small-cell lung cancer (NSCLC) harboring drug-sensitive EGFR mutations. However, the effectiveness of EGFR-TKI rechallenge after first-line EGFR-TKI treatment is not sufficient in elderly patients (over 75 years of age) harboring drug-sensitive EGFR mutations. Therefore, we investigated the effectiveness and safety of EGFR-TKI rechallenge after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations. Materials and Methods: Between April 2008 and December 2015, we analyzed 78 elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations with first-line EGFR-TKI treatment at four Japanese institutions. We retrospectively evaluated the clinical effectiveness and safety profiles of EGFR-TKI rechallenge after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Results: Twenty-two patients in the cohort were rechallenged with EGFR-TKI. The median age was 79.5 years (range 75–87 years). Despite the fact that it was a retrospective analysis, even with EGFR-TKI rechallenge treatment the response rate was 23%, progression-free survival was 5.3 months, and overall survival was 14.4 months. Common adverse events included rash acneiform, paronychia, diarrhea, and anorexia. There were no treatment-related deaths. Due to the occurrence of adverse events of grade 2 or more, dose reduction was performed in 15 (68.2%) of 22 cases. Conclusions: EGFR-TKI rechallenge treatment after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations was one of the limited, safe and effective treatment options for elderly EGFR-positive lung cancer patients.

Sign in / Sign up

Export Citation Format

Share Document