| General information |
| Database: | DB00062 |
| Objective: | Dacomitinib is an irreversible panEGFR family tyrosine kinase inhibitor. Findings from a phase 2 study in non small cell lung cancer showed favourable efficacy for dacomitinib compared with erlotinib. they aimed to compare dacomitinib with erlotinib in a phase 3 study. |
| Authors: | Ramalingam SS, et al |
| Title: | Dacomitinib versus erlotinib in patients with advancedstage, previously treated non small cell lung cancer (ARCHER 1009): a randomised, doubleblind, phase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 25439691 |
| Trial Design |
| Clinical Trial Id: | NCT01360554 |
| 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 (ARCHER I009): a randomised, doubleblind trial |
| Key Patients Feature: | 134 centres in 23 countries |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | erlotinib (150 mg/day) |
| Treatment Info: | they they randomly assigned patients in a 1:1 ratio to dacomitinib (45 mg/day) or erlotinib (150 mg/day) with matching placebo. Treatment allocation was masked to the investigator, patient, and study funder. |
| Primary End Point: | progression free survival per independent review for all randomly assigned patients, and for all randomly assigned patients with KRAS wildtype tumours. |
| Secondary End Point: | NA |
| Patients Number: | 878 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 33 patients (13%) in the dacomitinib group and 29 (11%)in the erlotinib group (twosided CochranMantelHaenszel p=0.261) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.6 vs 2.6;0.941, 95% CI 0.8021.104, onesided logrank p=0.229 |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | diarrhoea (47 [11%] );rash (29 [7%] ;stomatitis 15[3%];serious ADE 52 (12%) |
| Conclusions: | Irreversible EGFR inhibition with dacomitinib was not superior to erlotinib in an unselected patient population with advanced non small cell lung cancer or in patients with KRAS wildtype tumours. Further study of irreversible EGFR inhibitors should be restricted to patients with activating EGFR mutations. |