| General information |
| Database: | DB00644 |
| Objective: | In this study, they evaluated the efficacy of gefitinib alone without radiation therapy for the treatment of patients with BM from lung adenocarcinoma. |
| Authors: | Iuchi T, et al |
| Title: | Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFRmutant lung adenocarcinoma. |
| Journal: | Lung Cancer. |
| Year: | 2013 |
| PMID: | 24021541 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | brain metastases from EGFRmutant lung adenocarcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II trial |
| Key Patients Feature: | Eligibility criteria included newly radiographically diagnosedbrain metastasis from lung adenocarcinoma with mutations of epidermal growth factor receptor (EGFR), without history of chemotherapy using TKIs, with active extracranial lesions which required chemotherapy, age>18 years, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) score less than and equal to 2. Smoking history was not included in eligibility criteria but obtained during the patient's first evaluation. The mutation status of EGFR gene was evaluated by direct DNA sequencing using the original(primary) lung tumor. This study did not consider the types of EGFR mutations. Surgical resection of brain metastasis which caused the neurological symptoms did not preclude participation |
| Biomarker: | epidermal growth factor receptor (EGFR) mutations |
| Biomark Analysis: | In compared with L858R, exon 19 deletion was associated with better outcome of patients after treatment with gefitinib in both progression free (p = 0.003) and overall survival (p = 0.025). |
| Control Group Info: | single arm |
| Treatment Info: | Gefitinib was given at 250 mg orally once a day until tumor progression or unacceptable toxicity. |
| Primary End Point: | survival of patients after diagnosis of brain metastases |
| Secondary End Point: | progression free survival, time to salvage radiation therapy, radiologic response, and safety. |
| Patients Number: | 41 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The response rate was 87.8%. |
| Disease Control Rate: | NA |
| Median Time to Progression: | 14.5 (95% CI 10.2-18.3) months from diagnosis of brain metastases |
| Median PFS A vs. C: | 14.5 months (95% CI, 10.2-18.3 months) |
| Median OS A vs. C: | 21.9 months (95% CI, 18.5-30.3 months) |
| Adverse Event(agent arm): | Side effects were consisted mainly of skin toxicity. Skin disorders occurred in 27 (65.9%) cases. Grade 3 rash was progressed in 6 patients (14.6%), but skin disorders were not causes of discontinuity in any case. Liver dysfunction was also common after gefitinib. Grade 3 hepatobiliary events were observed in 5 (12.2%) cases, and chemotherapy was withdrawn in 1 case. Pulmonary events were very rare, but Grade 3 pneumonitis caused discontinuity of gefitinib in 1 case. |
| Conclusions: | Favorable response of BM to gefitinib even without irradiation was demonstrated. Exon 19 deletion was both a predictive and prognostic marker of patients with BM treated by gefitinib. |