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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
First- or second-line therapy with gefitinib produces equal survival in non-small cell lung cancer
Jenn-Yu Wu1, Chong-Jen Yu, Chih-Hsin Yang
1Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 10002, Taiwan.
Rationale:
Gefitinib is effective in treating patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Deletions in exon 19 and L858R in exon 21 are the best-documented EGFR mutations that are associated with effective gefitinib responsiveness.
Objectives:
To clarify the influence of gefitinib timing, we conducted a study to compare the outcomes of different lines of gefitinib treatment in patients with exon 19 deletions or L858R.
Methods:
We surveyed the clinical data and mutational studies of patients with NSCLC with EGFR mutations in the National Taiwan University Hospital (Taipei, Taiwan).
Measurements And Main Results:
Three hundred and twenty-eight patients, who received gefitinib for stage IIIb or IV NSCLC, were adequately sequenced for EGFR mutations; 192 patients had mutant EGFR, including 77 patients with exon 19 deletions and 75 patients with L858R. The 152 patients with exon 19 deletions or L858R and who were receiving gefitinib were classified into a chemonaive group (91 patients) or a chemotherapy-treated group (61 patients). Chemonaive status before gefitinib and female sex were associated with clinical response to gefitinib (P = 0.006 and 0.053, respectively). Neither overall survival after the start of antitumor therapy nor progression-free survival after gefitinib therapy was significantly different between these two groups (P = 0.207 and 0.804, respectively). Clinical response to gefitinib was the only factor associated with better overall survival (P = 0.001).
Conclusions:
This study suggests that gefitinib is effective in patients with EGFR mutations. The gefitinib response rate in chemonaive patients is higher than in chemotherapy-treated patients; however, there is no difference in overall survival.
Insights
Gefitinib is effective for non-small cell lung cancer (NSCLC) with EGFR mutations. While response rates are higher in treatment-naive patients, overall survival remains similar regardless of prior chemotherapy.
Area of Science:
- Oncology
- Medical Genetics
Background:
- Gefitinib is a targeted therapy for non-small cell lung cancer (NSCLC) patients with specific epidermal growth factor receptor (EGFR) mutations.
- Exon 19 deletions and L858R in exon 21 are key EGFR mutations linked to gefitinib efficacy.
Purpose of the Study:
- To investigate the impact of gefitinib treatment timing.
- To compare outcomes of gefitinib as a first-line versus later-line therapy in NSCLC patients with specific EGFR mutations (exon 19 deletions or L858R).
Main Methods:
- Retrospective analysis of clinical and mutational data from NSCLC patients at National Taiwan University Hospital.
- Patients with stage IIIb or IV NSCLC and EGFR mutations (exon 19 deletions or L858R) receiving gefitinib were categorized into treatment-naive or previously chemotherapy-treated groups.
Main Results:
- Of 328 sequenced patients, 192 had mutant EGFR. Among 152 patients with exon 19 deletions or L858R, 91 were treatment-naive and 61 had prior chemotherapy.
- Treatment-naive status and female sex were associated with higher clinical response rates to gefitinib.
- No significant differences in overall survival or progression-free survival were observed between the treatment-naive and chemotherapy-treated groups.
Conclusions:
- Gefitinib demonstrates effectiveness in NSCLC patients with EGFR mutations.
- Although gefitinib shows a higher response rate in treatment-naive patients, this does not translate to improved overall survival compared to patients who received prior chemotherapy.
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