Lung Cancer in 2013: State of the Art Therapy for Metastatic Disease

2013 ◽  
pp. 339-346
Author(s):  
Frances A. Shepherd ◽  
Paul A. Bunn ◽  
Luis Paz-Ares
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Poor Performance ◽  
Initial Therapy ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Molecular Features ◽  
Platinum Doublet

Lung cancer is the leading worldwide cause of cancer death and the majority of patients present with metastatic stage IV disease. At diagnosis, clinical, histologic, and molecular features must be considered in therapeutic decision-making for systemic therapy. Molecular testing for at least epidermal growth factor receptor ( EGFR) and ALK should be performed in all patients before therapy. Platinum doublet chemotherapy may be considered for “fit” patients who do not have a molecular driver genetic abnormality. Bevacizumab can be considered for addition to the doublet in patients with nonsquamous cancers who have no contraindications. A pemetrexed combination is considered only in nonsquamous histology. Patients with EGFR mutations or ALK fusions should be treated with erlotinib or crizotinib, respectively, even in patients with tumor-related poor performance. The tyrosine-kinase inhibitors (TKIs) may be continued until multisite, symptomatic progression. For patients initially treated with a platinum doublet, maintenance chemotherapy with pemetrexed, erlotinib, gemcitabine, or possibly docetaxel is an option with selection based on clinical features, histology, type of initial therapy, and response to first-line therapy.

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 Next-Generation Sequencing Reveals High Uncommon EGFR Mutations and Tumour Mutation Burden in a Subgroup of Lung Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Gang Guo ◽  
Gaofeng Li ◽  
Yinqiang Liu ◽  
Heng Li ◽  
Qi Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Kinase Inhibitors ◽  
The Cancer Genome Atlas ◽  
Egfr Mutations ◽  
Next Generation ◽  
Molecular Features ◽  
Mutation Burden ◽  
Incidence And Mortality ◽  
Generation Sequencing

Xuanwei County in Southwest China shows the highest incidence and mortality rate of lung cancer in China. Although studies have reported distinct clinical characteristics of patients from Xuanwei, the molecular features of these patients with non-small cell lung cancer (NSCLC) remain unclear. Here, we comprehensively characterised such cases using next-generation sequencing (NGS). Formalin-fixed, paraffin-embedded tumour samples from 146 patients from Xuanwei with NSCLC were collected for an NGS-based target panel assay; their features were compared with those of reference Chinese and The Cancer Genome Atlas (TCGA) cohorts. Uncommon EGFR mutations, defined as mutations other than L858R, exon 19del, exon 20ins, and T790M, were the predominant type of EGFR mutations in the Xuanwei cohort. Patients harbouring uncommon EGFR mutations were more likely to have a family history of cancer (p = 0.048). A higher frequency of KRAS mutations and lower frequency of rearrangement alterations were observed in the Xuanwei cohort (p < 0.001). Patients from Xuanwei showed a significantly higher tumour mutation burden than the reference Chinese and TCGA cohorts (p < 0.001). Our data indicates that patients from Xuanwei with NSCLC harbouring G719X/S768I co-mutations may benefit from treatment with EGFR-tyrosine kinase inhibitors. Our comprehensive molecular profiling revealed unique genomic features of patients from Xuanwei with NSCLC, highlighting the potential for improvement in targeted therapy and immunotherapy.

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.

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