| General information |
| Database: | DB00806 |
| Objective: | human epidermal growth factor receptor 2 mutations and amplifications have been identified as oncogenic drivers in lung cancers. Dacomitinib, an irreversible inhibitor of human epidermal growth factor receptor 2, EGFR (HER1), and HER4 tyrosine kinases, has demonstrated activity in cellline models with human epidermal growth factor receptor 2 exon 20 insertions or amplifications. Here, they studied dacomitinib in patients with human epidermal growth factor receptor 2mutant or amplified lung cancers. |
| Authors: | Kris MG, et al |
| Title: | Targeting human epidermal growth factor receptor 2 aberrations as actionable drivers in lung cancers:phase II trial of the panHER tyrosine kinase inhibitor dacomitinib in patients with human epidermal growth factor receptor 2mutant or amplified tumors. |
| Journal: | Ann Oncol. |
| Year: | 2015 |
| PMID: | 25899785 |
| Trial Design |
| Clinical Trial Id: | NCT00818441 |
| Agent: | dacomitinib
|
| Target: | Epidermal growth factor receptor, Proto oncogene proteinc mdm2, Erbb2 tyrosine kinase receptor
|
| Cancer Type: | lung cancer |
| Cancer Subtype: | advanced lung cancers with human epidermal growth factor receptor 2 mutations or amplification |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a prespecified cohort of a phase II study |
| Key Patients Feature: | patients with stage IIIB/IV lung cancers with human epidermal growth factor receptor 2 mutations or amplification. |
| Biomarker: | human epidermal growth factor receptor 2 mutations or amplification |
| Biomark Analysis: | Three of 26 patients with tumors harboring human epidermal growth factor receptor 2 exon 20 mutations [12%; 95% confidence interval (CI) 2% to 30%] had partial responses lasting 3+, 11, and 14 months. No partial responses occurred in four patients with tumors with human epidermal growth factor receptor 2 amplifications. The median overall survival was 9 months from the start of dacomitinib (95% CI 721 months) for patients with human epidermal growth factor receptor 2 mutations and ranged from 5 to 22 months with amplifications. |
| Control Group Info: | single arm |
| Treatment Info: | they gave oral dacomitinib at 3045 mg daily in 28day cycles. |
| Primary End Point: | partial response rate, overall survival, and toxicity. |
| Secondary End Point: | NA |
| Patients Number: | 30 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The overall response for the patients with human epidermal growth factor receptor 2mutant disease was 12% (95% CI 2% to 30%) and 0% (95% CI 0% to 60%) for the four patients with |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | For the human epidermal growth factor receptor 2mutant cohort, the median progression free survival was 3 months (95% CI 2-4 months). The four individuals with human epidermal growth factor receptor 2amplified tumors remained progression free for 1, 1, 5, and 5 months. |
| Median OS A vs. C: | 9 months from the start of dacomitinib (95% CI 721 months) for patients with human epidermal growth factor receptor 2 mutations and ranged from 5 to 22 months with amplifications. |
| Adverse Event(agent arm): | NA |
| Conclusions: | Dacomitinib produced objective responses in patients with lung cancers with specific human epidermal growth factor receptor 2 exon 20 insertions. This observation validates human epidermal growth factor receptor 2 exon 20 insertions as actionable targets and justifies further study of human epidermal growth factor receptor 2targeted agents in specific human epidermal growth factor receptor 2driven lung cancers. |