| General information |
| Database: | DB00784 |
| Objective: | Somatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non small cell lung cancer (non small cell lung cancer) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined firstline gefitinib in advanced non small cell lung cancer patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms. |
| Authors: | Sequist LV, et al |
| Title: | Firstline gefitinib in patients with advanced non small cell lung cancer harboring somatic EGFR mutations. |
| Journal: | J Clin Oncol. |
| Year: | 2008 |
| PMID: | 18458038 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer harboring epidermal growth factor receptor mutations |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II, prospective, multicenter trial |
| Key Patients Feature: | Chemotherapyna ve patients with advanced non small cell lung cancer with >or= 1 clinical characteristic associated with EGFR mutations |
| Biomarker: | EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. |
| Biomark Analysis: | EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutationpositive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q.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. |
| Control Group Info: | single arm |
| Treatment Info: | Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. |
| Primary End Point: | response rate. |
| Secondary End Point: | NA |
| Patients Number: | 98 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 55% (95% CI, 33 to 70) |
| Disease Control Rate: | 94% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 9.2 months (95% CI, 6.2 to 11.8) |
| Median OS A vs. C: | 17.5 months (95% CI, 13.5 to 21.3 months), and the 1year OS is 73% |
| Adverse Event(agent arm): | Treatmentrelated toxicity was generally mild. Rash and diarrhea were the most common events |
| Conclusions: | Firstline therapy with gefitinib administered in a genotypedirected fashion to patients with advanced non small cell lung cancer 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. |