Abstract | PURPOSE: PATIENTS AND METHODS:
Chemotherapy-naïve patients with advanced NSCLC with >or= 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. The primary outcome was response rate. RESULTS: Ninety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification. CONCLUSION: First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care.
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Authors | Lecia V Sequist, Renato G Martins, David Spigel, Steven M Grunberg, Alexander Spira, Pasi A Jänne, Victoria A Joshi, David McCollum, Tracey L Evans, Alona Muzikansky, Georgiana L Kuhlmann, Moon Han, Jonathan S Goldberg, Jeffrey Settleman, A John Iafrate, Jeffrey A Engelman, Daniel A Haber, Bruce E Johnson, Thomas J Lynch |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 26
Issue 15
Pg. 2442-9
(May 20 2008)
ISSN: 1527-7755 [Electronic] United States |
PMID | 18458038
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Quinazolines
- ErbB Receptors
- Gefitinib
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Topics |
- Adenocarcinoma
(drug therapy, genetics, secondary)
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(therapeutic use)
- Carcinoma, Large Cell
(drug therapy, genetics, secondary)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, genetics, secondary)
- Central Nervous System Neoplasms
(drug therapy, genetics, secondary)
- Disease-Free Survival
- ErbB Receptors
(antagonists & inhibitors, genetics)
- Female
- Gefitinib
- Humans
- In Situ Hybridization, Fluorescence
- Lung Neoplasms
(drug therapy, genetics, pathology)
- Male
- Middle Aged
- Mutation
(genetics)
- Neoplasm Staging
- Prospective Studies
- Quinazolines
(therapeutic use)
- Survival Rate
- Treatment Outcome
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