| General information |
| Database: | DB00769 |
| Objective: | This randomized, openlabel trial compared dacomitinib (PF00299804), an irreversible inhibitor of human epidermal growth factor receptors (EGFR)/HER1, human epidermal growth factor receptor 2, and HER4, with erlotinib, a reversible EGFR inhibitor, in patients with advanced non small cell lung cancer (non small cell lung cancer). |
| Authors: | Ramalingam SS, et al |
| Title: | Randomizedphase II study of dacomitinib (PF00299804), an irreversible panhuman epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non small cell lung cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22753918 |
| Trial Design |
| Clinical Trial Id: | NCT00769067 |
| Agent: | dacomitinib erlotinib
|
| Target: | NA
|
| 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: | Randomizedphase II study |
| Key Patients Feature: | Patients with non small cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 2, no prior HERdirected therapy, and one/two prior chemotherapy regimens |
| Biomarker: | KRAS/EGFR mutation status |
| Biomark Analysis: | PFS benefit was observed in most clinical and molecular subsets, notably KRAS wildtype/EGFR any status, KRAS wildtype/EGFR wildtype, and EGFR mutants. |
| Control Group Info: | dacomitinib versus erlotinib |
| Treatment Info: | pts received dacomitinib 45 mg or erlotinib 150 mg once daily. |
| Primary End Point: | progression free survival (PFS), between dacomitinib and erlotinib. |
| Secondary End Point: | best overall response rate (RR), duration of response (DR), overall survival (OS), safety, and patientreported outcomes (PRO) of healthrelated quality of life (HRQoL) and disease/treatmentrelated symptoms. Exploratory end points included determination of EGFR and KRAS mutations in tumor tissue and evaluation of dacomitinib trough concentrations after repeated dosing. |
| Patients Number: | 188 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 17.00% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.86 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (hazard ratio [HR] = 0.66; 95% CI, 0.47 to 0.91; twosided P = .012) |
| Median OS A vs. C: | 9.53 months for patients treated with dacomitinib and 7.44 months for patients treated with erlotinib (HR = 0.80; 95% CI, 0.56 to 1.13; twosided P = .205). |
| Adverse Event(agent arm): | Adverse events necessitating treatment withdrawal were uncommon in both treatment arms. Seven patients discontinued in the dacomitinib arm, five with grade 1 to 3 dermatologic skin toxicity (including four during the first month of treatment), one with grade 2 diarrhea, and one with grade 3 dehydration. Two patients discontinued in the erlotinib group, one with grade 2 nausea and one with grade 2 malaise |
| Conclusions: | Dacomitinib demonstrated significantly improved PFS versus erlotinib, with acceptable toxicity. PFS benefit was observed in most clinical and molecular subsets, notably KRAS wildtypeEGFR any status, KRAS wildtypeEGFR wildtype, and EGFR mutants |