Treatment outcomes with tyrosine kinase inhibitors in patients with uncommon EGFR mutations in non-small cell lung cancer: A multi-centre retrospective analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20678-e20678
Author(s):  
Sarah Hunter ◽  
Guillermina Nickless ◽  
Karim El-Shakankery ◽  
Nadia Yousaf ◽  
Daniel Smith ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Stable Disease ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Tki Treatment ◽  
Exon 20 ◽  
Nsclc Patients

e20678 Background: The clinical significance of common epidermal growth factor receptor (EGFR) mutations (exon 19 deletions and exon 21 L858 mutations) in non-small cell lung cancer is well known1. However, 2-8% of NSCLC patients harbour an uncommon EGFR mutation2. Prognosis and response to tyrosine kinase inhibitors (TKIs) is unclear in this subgroup. The most frequent uncommon EGFR mutations are exon 18 G719 and exon 21 L861. Although not frequently reported, these appear to have favourable outcomes with TKIs3. Methods: We conducted a retrospective review of all patients with uncommon EGFR mutations identified at laboratories in 4 UK centres, between 2012 and 2016. Patient’s not treated with a TKI were excluded. Techniques including cold PCR were in use at contributing laboratories. The T790M resistance mutation was excluded from our study. For patients with uncommon EGFR mutations, patient characteristics and response to TKIs were analysed. Results: 29 patients with uncommon EGFR mutations, with both rare point mutations (86%) and deletions (14%), were identified. All patients were treated with a TKI. Age ranged from 37 to 85 (median 67). The majority (86%) of patients were performance status 1. TKIs used were afatinib (31%), gefitinib (24%) and erlotinib (45%). 19 patients (66%) benefitted from TKI treatment (38% partial response (PR), 28% stable disease (SD). 10 patients (34%) did not respond, including all four with exon 20 mutations. 15 mutations were exon 18 G719 mutations: 40% had a PR and 40% stable disease with TKI therapy. There were two L861 mutations, both responded with a PR. 13 patients remained on TKI treatment at data cut off. The median progression free survival at this time was 8.1months. Tabulated details of response according to mutation will be presented. Conclusions: The majority (66%) of NSCLC patients with uncommon EGFR mutations benefitted from TKI therapy in this series. These high clinical benefit rates, typified by patients with G719 mutation, are in line with the limited previous reports 1,3. Exon 20 mutations were associated with TKI resistance, in line with the literature4.

Response to Osimertinib in a Patient With Non-Small Cell Lung Cancer and Two Uncommon EGFR mutations

2020 ◽  
pp. 10-13
Author(s):  
Christoforos Astaras ◽  
Adrienne Bettini ◽  
Daniel C. Betticher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Genetic Alterations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20

In advanced non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations are one of the most frequent oncogenic drivers. They confer a favorable prognosis and strongly predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Over the last decades, several EGFR genetic alterations, common and uncommon mutations, have been described in exons 18−21. Common mutations are exon 19 deletions (most frequently E746-A750) and exon 21 L858R substitution. Uncommon mutations include exon 18 G719X, exon 20 S768l, exon 21 L861Q and many other rare ones. This report describes the case of a 55-year-old woman with a newly diagnosed metastatic lung adenocarcinoma harboring two rare EGFR mutations and showing sustained response to osimertinib.

Assessment of EGFR mutations in patients diagnosed of squamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18106-e18106
Author(s):  
Francisco Lobo ◽  
Manuel Domine ◽  
Federico Rojo ◽  
Yann Izarzugaza ◽  
Ana Leon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20 ◽  
Nsclc Patients

e18106 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better outcome to EGFR tyrosine kinase inhibitors than platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies with Caucasian patients have shown a prevalence of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in squamous-cell NSCLC patients from an area of influence of 500,000 habitants. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletion, 9 (50%) exon 21 mutations (7 L858R and 2 L861Q) and 3 (16.6%) cases exon 20 insertion. In the EGFR mutated population, 16 (88.88%) patients were diagnosed as adenocarcinoma and 2 (11.11%) as squamous cell carcinoma. The characteristics of these squamous cell cancer patients were: 2 male; 1 non-smoker, 1 former-smoker; 1 stage IV and 1 stage IB at diagnosis; one case exon 20 insertion and one exon 21 mutation (L858R). Conclusions: The EGFR mutation rate in squamous-cell NSCLC patients in our referral area is superior (11.17%) than previously reported, reinforcing the importance of including EGFR mutation testing in squamous-cell NSCLC population for selecting optimal therapy for these patients.

scholarly journals Clinical characteristics of advanced non-small cell lung cancer patients with EGFR exon 20 insertions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chie Morita ◽  
Tatsuya Yoshida ◽  
Masayuki Shirasawa ◽  
Ken Masuda ◽  
Yuji Matsumoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Characteristics ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Line Therapy ◽  
Exon 20 ◽  
Nsclc Patients

AbstractEpidermal growth factor receptor (EGFR) exon 20 insertion mutations (Exon20ins) account for 4–12% of all EGFR mutations in non-small cell lung cancer (NSCLC) patients. Data on the differences in clinical characteristics between patients with Exon20ins and major mutations (M-mut) such as exon 19 deletion and L858R are limited. We retrospectively reviewed advanced NSCLC patients with EGFR mutations, who were treated with systemic therapy between January 2011 and December 2019. We identified 23 patients with Exon20ins and 534 patients with M-mut. In Exon20ins patients, the median age was 60 (range 27–88) years, and females and never-smokers were predominant. Clinical characteristics were similar in the two groups. In Exon20ins patients, 17 patients received platinum doublet as first-line therapy, and the overall response rate (ORR) and median progression-free survival (mPFS) were 11.8% and 8.9 months. Additionally, seven patients received conventional EGFR-tyrosine kinase inhibitors (TKIs), and eight patients anti-PD-1 antibodies in any-line therapy. ORR and mPFS of EGFR-TKIs and anti-PD-1 antibodies were 0%, 2.2 months and 25%, 3.1 months, respectively. Overall survival was significantly shorter in Exon20ins patients than in M-mut patients (29.3 vs. 43.4 months, p = 0.04). The clinical outcomes in Exon20ins patients were not satisfactory compared to M-mut patients.

Immunotherapy in advanced non-small-cell lung cancer with EGFR mutations

Immunotherapy ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1195-1207
Author(s):  
Fangfang Liu ◽  
Xun Yuan ◽  
Jizong Jiang ◽  
Qian Chu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tkis

EGFR-tyrosine kinase inhibitors (EGFR-TKIs) had been regarded as the front-line treatment for advanced non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to EGFR-TKIs is inevitable, it remains a major challenge. Immune checkpoint inhibitors (ICIs) had shown superior clinical efficacy in many types of solid tumors, while it exhibited impaired overall efficacy in NSCLC with  EGFR mutations. In this review, we will perform a meta-analysis to assess the relationship between the programmed death ligand 1 (PD-L1) expression and clinical benefit of EGFR-TKIs. We also overview the immunotherapy in advanced NSCLC patients with EGFR mutations to investigate the potential biomarkers predicting the ICIs efficiency, and the subgroups that could benefit from ICIs treatment.

scholarly journals Real-world Outcomes of First-line Afatinib in Patients with Non-small Cell Lung Cancer and Uncommon EGFR Mutations in South Korea

2021 ◽  
Author(s):  
Mi-Hyun Kim ◽  
Chang Min Choi ◽  
Sung Yong Lee ◽  
Cheol Kyu Park ◽  
Yoon Soo Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20

Abstract Uncommon epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are heterogeneous and show variable prevalence and clinical responses to EGFR-tyrosine kinase inhibitors. We investigated the characteristics of uncommon EGFR mutations and the clinical efficacy of afatinib in patients. In this multicenter, retrospective study, we analyzed patients with NSCLC and uncommon EGFR mutations; these were categorized according to their incidence: (1) major uncommon mutations (G719X and L861Q), (2) compound mutations, and (3) minor uncommon mutations (exon 20 insertion, S768I, and de novo T790M). Sixty-four patients (9.1%, 64/703) with uncommon EGFR mutations were identified in 16 South Korean institutes. Afatinib demonstrated activity against major uncommon (median time of treatment [TOT]: 20.3 months, 95% CI: 5.0-27.9; overall survival (OS): 30.6 months, 95% CI: 33.5–34.0) and compound mutations (median TOT: 11.9 months, 95% CI: 3.6–9.6; OS: 29.1 months, 95% CI: 12.1–65.4). Minor uncommon mutations showed unfavorable responses to afatinib (median TOT: 3.8 months, 95% CI: 2.1–4.2; OS: 8.5 months, 95% CI: 4.7–18.2). S768I mutation was present in 14 patients (1.99%, 14/703). Median TOT and OS were not significantly different between S768I and resistant exon 20 mutations. Afatinib is active in patients with NSCLC harboring major uncommon and compound EGFR mutations.

Targeting HER2 Alterations in Non–Small-Cell Lung Cancer: A Comprehensive Review

2020 ◽  
pp. 411-425 ◽  
Author(s):  
Jing Zhao ◽  
Yang Xia
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Antitumor Agents ◽  
De Novo ◽  
Point Mutations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Exon 20

PURPOSE HER2 is a critical gene that drives various solid tumors in addition to those of breast cancer. For example, HER2 plays a role in non–small-cell lung cancer (NSCLC). Overexpression, amplification, and point mutations in HER2 have been described in patients with NSCLC; however, the potential roles of these alterations remain unclear. METHODS We summarize the evidence regarding the distinct impacts of different HER2 aberrations on antitumor agents. Also, we update the therapeutic efficacy of HER2-targeted agents, including anti-HER2 antibodies, antibody-drug conjugates, and small-molecule tyrosine kinase inhibitors, tested in HER2-aberrant NSCLC. RESULTS Although these drugs are not yet standard treatments, certain patients may benefit from these therapies. In this review, we aim to provide an improved understanding of HER2 aberrations in NSCLC, including NSCLC biology and the impacts of each aberration on prognosis and standard treatment. We also highlight the potential of novel anti-HER2 therapies approved by regulatory bodies and those in clinical development. CONCLUSION Compared with HER2 amplification or overexpression, HER2 mutations, especially HER2 exon 20 mutations, are emerging as the most clear targetable driver for HER2-directed therapies in lung cancer. De novo and inducible HER2 pathway activation need to be differentially managed. Further investigations with new strategies are needed.

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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