| General information |
| Database: | DB00639 |
| Objective: | Icotinib is a new firstgeneration epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. a phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with wholebrain radiotherapy (WBRT) in Chinese non small cell lung cancer patients with brain metastases (BMs); the cerebrospinal fluid (CSF)/plasma concentrations of icotinib were also investigated. |
| Authors: | Fan Y, et al |
| Title: | a phase II study of icotinib and wholebrain radiotherapy in Chinese patients with brain metastases from non small cell lung cancer. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2015 |
| PMID: | 26148750 |
| Trial Design |
| Clinical Trial Id: | NCT01514877 |
| Agent: | icotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | brain metastases from non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 4 |
| Therapeutic Combination Content: | icotinib and wholebrain radiotherapy |
| Study Type: | phase II study |
| Key Patients Feature: | non small cell lung cancerpatients with BMs newly confirmed by magnetic resonanceimaging (MRI); leptomeningeal involvement were notallowed; clearly confirmed non small cell lung cancer by pathology; patientswho had not received EGFRTKI treatment; patients whohad not received WBRT; time from the last chemotherapymore than and equal to 4 weeks; evaluable lesions; multiple intracranial lesionsor single lesion not suitable for surgery or stereotacticradiotherapy; age more than and equal to 18 and less than and equal to 75 years; Eastern Cooperative Oncology Group performance status (ECOG PS)score, 0-2; EGFR detection method using the amplification refractory mutation system (ARMS). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Icotinib was administered at 125 mg orally 3 times/day until tumor progression or unacceptable toxicity, concurrently with WBRT (3.0 Gy per day, 5 days per week, to 30 Gy). CSF and plasma samples were collected simultaneously from 10 patients. Icotinib concentrations in the CSF and plasma were measured by highperformance liquid chromatography coupled with tandem mass spectrometry. |
| Primary End Point: | median PFS (including intracranialand extracranial lesions) |
| Secondary End Point: | the OS, the overall response rate (ORR), and safety. |
| Patients Number: | 20 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 0.95 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.0 months (95 % CI 1.2-13.2 months) |
| Median OS A vs. C: | 14.6 months (95 % CI 12.5- 16.7 months) |
| Adverse Event(agent arm): | During the icotinibcombined WBRT, 45.0 % of patients had nausea, 35.0 % of patients experienced headaches, and 10 % of patients had vomiting, which were grade 1 adverse reactions. The most common AEs reported during icotinib alone therapy were rash (40.0 %), diarrhea (15.0 %), and increased AST/ALT (15.0 %). These were predominantly of grade 1/2, with only one case of increased AST/ALT reported as grade 3. |
| Conclusions: | Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from non small cell lung cancer. This clinical benefit was related to the presence of activating EGFR mutations. |