| General information |
| Database: | DB00641 |
| Objective: | The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, human epidermal growth factor receptor 2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/MSCCHN). |
| Authors: | Kim HS, et al |
| Title: | Phase II clinical and exploratory biomarker study of dacomitinib in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. |
| Journal: | Clin Cancer Res. |
| Year: | 2015 |
| PMID: | 25424851 |
| Trial Design |
| Clinical Trial Id: | NCT01449201 |
| Agent: | dacomitinib
|
| Target: | Epidermal growth factor receptor, Proto oncogene proteinc mdm2, Erbb2 tyrosine kinase receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced squamous cell carcinoma of the head and neck |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multicenter, phase II study |
| Key Patients Feature: | Patients with histologically confirmed R/MSCCHN wereenrolled. Patients were at least the age of 18 years, had an EasternCooperative Oncology Group performance status (ECOGPS) of0 to 2, had at least one measurable disease, had documentedprogressive diseases after platinumbased systemic chemotherapyfor R/MSCCHN, and had a life expectancy of at least 3 months.Chemotherapyna€ ve patients with borderline renal function forplatinum administration or ECOGPS2 were allowed to enter thestudy at the physician's discretion. Previous treatmentswith EGFR mAbs were allowed. |
| Biomarker: | somatic mutation, gene copy number, gene expression, p16(INK4A) expression by IHC |
| Biomark Analysis: | Mutations in the PI3K pathway (PIK3CA, PTEN) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005). |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated with dacomitinib 45 mg/day. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16(INK4A) expression by IHC, and investigation of their relationship with clinical outcomes. |
| Primary End Point: | ORR |
| Secondary End Point: | clinical benefit (CB; PFS4 months on dacomitinib), PFS, OS, and the safety profile. Exploratory objectives were to evaluate whether tumor somatic mutation, copy number change, or gene expression is correlated with clinical outcomes. |
| Patients Number: | 48 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. |
| Disease Control Rate: | 0.858 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.9 months [95% confidence interval (CI), 2.9-5.0] |
| Median OS A vs. C: | 6.6 months (95% CI, 5.4-10.3). |
| Adverse Event(agent arm): | AEs were mostly grade 1 to 2 and easily manageable. The most common AEs were paronychia (65%) and diarrhea (52%). Treatmentrelated grade 3 AEs occurred in 6 patients. At least one dose interruption and reduction due to treatmentrelated AEs occurred in 24 patients (50%) and 9 (19%). |
| Conclusions: | Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinumfailed RMSCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which RMSCCHN patients are likely to gain benefit from dacomitinib. |