scholarly journals Successful Treatment of Afatinib-Refractory Non-Small Cell Lung Cancer with Uncommon Complex EGFR Mutations Using Pembrolizumab: A Case Report

2019 ◽  
Vol 12 (2) ◽  
pp. 564-567
Author(s):  
Yuri Taniguchi ◽  
Momoko Yamamoto ◽  
Hiroaki Ikushima ◽  
Sayaka Ohara ◽  
Hideyuki Takeshima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Stage ◽  
Nsclc Patient ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Rapid Progression ◽  
Small Cell Lung

Although there has been significant progress in immune-checkpoint inhibitor (ICI) treatment, it remains controversial whether they should be used in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). We herein report the case of an NSCLC patient with uncommon complex EGFR mutations (G719S and L861Q) who was refractory to afatinib treatment but who showed a good response to pembrolizumab treatment. A 65-year-old female ex-smoker was diagnosed with right upper lobe NSCLC (clinical stage IVB; cT2bN3M1c). She had received afatinib for two months, but her disease showed rapid progression. Pembrolizumab treatment was initiated because more than 75% of her tumor cells expressed PD-L1. Her tumor responded well to pembrolizumab treatment and it remained effective for more than 1 year. Our case suggests that pembrolizumab treatment is a treatment option for NSCLC patients with uncommon EGFR mutations and high PD-L1 expression levels who are refractory to EGFR-TKI treatment.

scholarly journals Continued gefitinib retreatment beyond progression in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052095503
Author(s):  
Xuhong Jiang ◽  
Xiaoqing Li ◽  
Lingli Tu ◽  
Jin Cai ◽  
Man Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung

Purpose To evaluate the effectiveness and safety of gefitinib retreatment beyond disease progression in patients with advanced non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor ( EGFR) mutations. Methods Data from patients with stage III/IV NSCLC were analyzed retrospectively. Patients with sensitive EGFR mutations received first-line treatment with gefitinib followed by retreatment with gefitinib after disease progression. Progression-free survival (PFS) after the first treatment (PFS-1) was defined as the time to progression or death using the Response Evaluation Criteria in Solid Tumors criteria (RECIST) v1.1 criteria. The second PFS (PFS-2) was defined as the interval between the first and second progressions, at the investigator’s discretion. Toxicities were recorded in accordance with the National Cancer Institute (NCI)-Common Terminology Criteria (CTC) version 4.0. Results Sixteen patients aged 53 to 80 years (median 66 years) were included in the analysis. The median PFS-1 and PFS-2 were 10.0 months and 14.0 months, respectively. The median overall survival (OS) was 36.0 months. No toxicity of grade 3 or worse was observed. Conclusions Our findings suggest that gefitinib retreatment beyond disease progression may be an effective and tolerable approach for NSCLC patients with sensitive EGFR mutations.

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.

Frequency and types of EGFR mutations in Moroccan patients with non–small cell lung cancer

2020 ◽  
pp. 030089162096457
Author(s):  
Mohamed Lemine Sow ◽  
Hind El Yacoubi ◽  
Badreddine Moukafih ◽  
Salif Balde ◽  
Gloria Akimana ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Smoking Status ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Asian Populations ◽  
Moroccan Patients

Background: Mutations in the epidermal growth factor receptor ( EGFR) gene are commonly observed in non-small cell lung cancer (NSCLC), particularly in adenocarcinoma histology. The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion reported in Asian populations than Caucasian populations. There is a lack of data on these mutations in north Africa. Methods: Tumor specimens from Moroccan patients with NSCLC were collected from five pathology laboratories between November 2010 and December 2017 to determine frequency and types of EGFR mutations. Tumors were tested in a reference center for EGFR by polymerase chain reaction and sequencing of exons 18, 19, 20, and 21. Results: A total of 334 patients were enrolled: 242 (72.5%) males and 92 females (27.5%). A total of 56.9% had a history of smoking. EGFR testing of the 334 lung adenocarcinoma samples demonstrated a wild-type EGFR in 261 (78.1%) and mutated EGFR in 73 (21.9%). Mutations were mainly detected in the exon 19 deletion (65.8%), followed by exon 21 L858 (17.8%) and other exon 21 codon mutations (5.5%) and exon 18 (6.8%), whereas primary mutations of exon 20 were less frequent (4.1%). In patients with advanced NSCLC, the detection of EGFR mutation was independently associated with sex (41.3% female vs 14.5% male; p < 0.001) and smoking status (34.8% nonsmokers vs 12.9% active smokers; p < 0.001). The mean age was significantly different between the two groups ( p = 0.041). Conclusion: Our findings confirm the genetic heterogeneity of NSCLC worldwide, reporting frequency of EGFR mutations in Moroccan patients with NSCLC between those of Asian and Caucasian populations.

scholarly journals PD-L1 expression and response to pembrolizumab in patients with EGFR-mutant non-small cell lung cancer

2020 ◽  
Vol 50 (5) ◽  
pp. 617-622
Author(s):  
Eriko Miyawaki ◽  
Haruyasu Murakami ◽  
Keita Mori ◽  
Nobuaki Mamesaya ◽  
Takahisa Kawamura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Poor Response ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Egfr Mutant

Abstract Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer is less likely to express programmed death-ligand 1 (PD-L1) than tumors with wild-type EGFR and is associated with poor response to pembrolizumab. To understand the relationship between EGFR mutation and PD-L1 expression in pembrolizumab response, we retrospectively evaluated the factors contributing to the high tumor proportion score in 155 EGFR-mutant non-small cell lung cancer cases and their associated response to pembrolizumab. Uncommon EGFR mutations were significantly associated with a PD-L1 tumor proportion score ≥ 50% compared to common EGFR mutations. The objective response rate to pembrolizumab of 14 patients was 36%, including 22% in patients with common EGFR mutations, 60% in patients with uncommon EGFR mutations and 75% in patients with both uncommon mutations and a PD-L1 tumor proportion score ≥ 50%. A PD-L1 tumor proportion score ≥ 50% was more frequent in non-small cell lung cancer patients harboring uncommon EGFR mutations and was associated with pembrolizumab efficacy.

scholarly journals Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

2022 ◽  
Vol 29 (1) ◽  
pp. 255-266
Author(s):  
Ilaria Attili ◽  
Antonio Passaro ◽  
Pasquale Pisapia ◽  
Umberto Malapelle ◽  
Filippo de Marinis
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.

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.

scholarly journals Combination of Crizotinib and Osimertinib in T790M+ EGFR-Mutant Non-Small Cell Lung Cancer with Emerging MET Amplification Post-Osimertinib Progression in a 10-Year Survivor: A Case Report

2021 ◽  
pp. 477-482
Author(s):  
Miriam Blasi ◽  
Daniel Kazdal ◽  
Michael Thomas ◽  
Petros Christopoulos ◽  
Mark Kriegsmann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Met Amplification ◽  
Egfr Mutant

Tyrosine kinase inhibitors (TKIs) represent the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The duration of the response is, however, limited in time owing to the development of resistance mechanisms to both first- and second-generation agents such as MET oncogene amplification. This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.

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