scholarly journals Clinical outcomes and secondary epidermal growth factor receptor (EGFR) T790M mutation among first‐line gefitinib, erlotinib and afatinib‐treated non‐small cell lung cancer patients with activating EGFR mutations

2019 ◽  
Vol 144 (11) ◽  
pp. 2887-2896 ◽  
Author(s):  
Yen‐Ting Lin ◽  
Jin‐Shing Chen ◽  
Wei‐Yu Liao ◽  
Chao‐Chi Ho ◽  
Chia‐Lin Hsu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
T790m Mutation ◽  
Lung Cancer Patients ◽  
Epidermal Growth ◽  
Egfr T790m

First-Line Gefitinib for Patients With Advanced Non–Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations Without Indication for Chemotherapy

2009 ◽  
Vol 27 (9) ◽  
pp. 1394-1400 ◽  
Author(s):  
Akira Inoue ◽  
Kunihiko Kobayashi ◽  
Kazuhiro Usui ◽  
Makoto Maemondo ◽  
Shoji Okinaga ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Nucleic Acid ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Epidermal Growth

Purpose This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations without indication for chemotherapy as a result of poor performance status (PS). Patients and Methods Chemotherapy-naïve patients with poor PS (patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4, 75 to 79 years of age with PS 2 to 4, and ≥ 80 years of age with PS 1 to 4) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib (250 mg/d) alone. Results Between February 2006 and May 2007, 30 patients with NSCLC and poor PS, including 22 patients with PS 3 to 4, were enrolled. The overall response rate was 66% (90% CI, 51% to 80%), and the disease control rate was 90%. PS improvement rate was 79% (P < .00005); in particular, 68% of the 22 patients improved from ≥ PS 3 at baseline to ≤ PS 1. The median progression-free survival, median survival time, and 1-year survival rate were 6.5 months, 17.8 months, and 63%, respectively. No treatment-related deaths were observed. Conclusion This is the first report indicating that EGFR mutation-positive patients with extremely poor PS benefit from first-line gefitinib. Because there previously has been no standard treatment for these patients with short life expectancy other than best supportive care, examination of EGFR mutations as a biomarker is recommended in this patient population.

scholarly journals Osimertinib in the treatment of patients with epidermal growth factor receptor T790M mutation-positive metastatic non-small cell lung cancer: clinical trial evidence and experience

2016 ◽  
Vol 10 (6) ◽  
pp. 549-565 ◽  
Author(s):  
Ivana Sullivan ◽  
David Planchard
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Epidermal Growth Factor Receptor ◽  
Resistance Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Epidermal Growth ◽  
Egfr T790m

Patients with advanced epidermal growth factor receptor ( EGFR) mutant non-small cell lung cancer (NSCLC) are particularly sensitive to treatment with first- or second-generation EGFR tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib, which block the cell-signaling pathways that drive the growth of tumor cells. Unfortunately, the majority of patients develop resistance to them after a median duration of response of around 10 months, and in over half of these patients the emergence of the EGFR T790M resistance mutation is detected. Osimertinib is an oral, highly selective, irreversible inhibitor of both EGFR-activating mutations and the T790M-resistance mutation, while sparing the activity of wild-type EGFR. This article reviews clinical trial development of osimertinib in patients with NSCLC, presenting efficacy and safety evidence for its value in the EGFR T790M mutation-positive population and in different settings, including patients with metastatic disease. The preclinical background of clinically acquired resistance to osimertinib is presented and the combination tactics being investigated in an attempt to circumvent this are addressed.

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