| General information |
| Database: | DB00063 |
| Objective: | Dacomitinib is an irreversible panHER tyrosinekinase inhibitor with preclinical and clinical evidence of activity in non small cell lung cancer. they designed BR.26 to assess whether dacomitinib improved overall survival in heavily pretreated patients with this disease. |
| Authors: | Ellis PM, et al |
| Title: | Dacomitinib compared with placebo in pretreated patients with advanced or metastatic non small cell lung cancer (NCIC CTG BR.26): a doubleblind, randomised, phase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 25439692 |
| Trial Design |
| Clinical Trial Id: | NCT01000025 |
| Agent: | dacomitinib
|
| Target: | Epidermal growth factor receptor, Proto oncogene proteinc mdm2, Erbb2 tyrosine kinase receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase III (NCIC CTG BR.II6):doubleblind, randomised, placebocontrolled, |
| Key Patients Feature: | from 75 centres in 12 countries |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo |
| Treatment Info: | pts were then randomly allocated 2:1 to oral dacomitinib 45 mg oncedaily or matched placebo centrally via a theybbased system. Treatment continued until disease progression or unacceptable toxicity. |
| Primary End Point: | overall survival in the intentiontotreat population |
| Secondary End Point: | overall survival in predefined molecular subgroups, progression free survival, the proportion of patients who achieved an objective response, safety, and quality of life. |
| Patients Number: | 720 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | a significantly greater proportion of patients inthe dacomitinb group achieved an objective response than in the placebo group (34 [7%] of 480 patients vs three [1%] of240 patients, respectively; p=0.001). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.66 vs 1.38; 0.66 [95% CI 0.55-0.79]; p<0.0001 |
| Median OS A vs. C: | 6.83 vs 6.31;1.00 [95% CI 0.83-1.21]; p=0.506 |
| Adverse Event(agent arm): | diarrhoea, acneiform rash, oral mucositis, fatigue |
| Conclusions: | Dacomitinib did not increase overall survival and cannot be recommended for treatment of patients with advanced non small cell lung cancer previously treated with chemotherapy and an EGFR tyrosinekinase inhibitor. |