| General information |
| Database: | DB00807 |
| Objective: | Patients with EGFRmutant non small cell lung cancer generally have a progression free survival of 913 months while being treated with the EGFR tyrosinekinase inhibitors gefitinib or erlotinib. however, resistance inevitably develops, and more effective EGFR inhibitors are needed. Dacomitinib is a covalent panHER inhibitor that has shown clinical activity in patients previously treated with gefitinib or erlotinib. they did a trial of dacomitinib as initial systemic therapy in clinically and molecularly selected patients with advanced non small cell lung cancer. |
| Authors: | J nne PA, et al |
| Title: | Dacomitinib as firstline treatment in patients with clinically or molecularly selected advanced non small cell lung cancer: a multicentre, openlabel, phase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 25456362 |
| Trial Design |
| Clinical Trial Id: | NCT00818441 |
| 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: | openlabel, multicentre, phase II trial |
| Key Patients Feature: | treatmentnaive patients with advanced lung cancer who had clinical (neversmokers [<100 cigarettes per lifetime] or former light smokers [<10 packyears per lifetime] and more than and equal to 15 years since last cigarette) or molecular (EGFR mutation, regardless of smoking status) characteristics associated with response to EGFR inhibitors. |
| Biomarker: | EGFR mutation, regardless of smoking status |
| Biomark Analysis: | progression free survival at 4 months was 76.8% (95% CI 66.484.4) in the asenrolled population, and was 95.5% (95% CI 83.298.9) in the EGFRmutant population. |
| Control Group Info: | single arm |
| Treatment Info: | they gave dacomitinib orally once daily (45 mg or 30 mg) until progressive disease, unacceptable toxicity, or patient withdrawal. They used Response Evaluation Criteria in Solid Tumors criteria (version 1.0) to investigate the activity of dacomitinib in all patients with a baseline scan and at least one posttreatment scan, with investigator assessment of response and progression. |
| Primary End Point: | progression free survival at 4 months in the asenrolled population, with a null hypothesis of progression free survival at 4 months of 50% or less. |
| Secondary End Point: | NA |
| Patients Number: | 89 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 75.6% (95% CI 60.5-87.1) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 11.5 months (95% CI 9.0-12.9) |
| Median OS A vs. C: | 29.5 months (95% CI 22.8-35.6) |
| Adverse Event(agent arm): | The most common treatmentrelated adverse events were diarrhoea in 83 (93%) patients, dermatitis acneiform in 69 (78%) patients, dry skin in 39 (44%) patients, and stomatitis in 36 (40%) patients |
| Conclusions: | Dacomitinib had encouraging clinical activity as initial systemic treatment in clinically or molecularly selected patients with advanced non small cell lung cancer |