| General information |
| Database: | DB00333 |
| Objective: | Head and neck cancer associated with the chewing of betel preparations, including tobacco, is common to South East Asia. they report a phase IIB study in which ninetytwo treatment na ve patients with advanced squamous cell carcinoma received standard therapy with or without an antiEpidermal Growth Factor Receptor (EGFR) monoclonal antibody (Nimotuzumab). |
| Authors: | Basavaraj C, et al |
| Title: | Nimotuzumab with chemoradiation confers a survival advantage in treatmentna ve head and neck tumors over expressing EGFR. |
| Journal: | Cancer Biol Ther. |
| Year: | 2010 |
| PMID: | 20647773 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | nimotuzumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Nimotuzumab+chemoradiation |
| Study Type: | a phase IIB study |
| Key Patients Feature: | patients with advanced squamous cell carcinoma |
| Biomarker: | EGFR overexpression |
| Biomark Analysis: | Although EGFR expression showed a significant relationship to patient survival in patients treated with Nimotuzumab and chemoradiation (p=0.02), pMAPK expression did not (p=0.07). Interestingly, EGFR overexpression (as defined by mR3) correlated directly with overall survival in this group (p=0.01). |
| Control Group Info: | single arm |
| Treatment Info: | Marker expression in tumor adjacent sections was evaluated by immunohistochemistry. The clinical benefit of Nimotuzumab (200 mg/dose, once a week for six weeks) in combination with radiotherapy or chemoradiation was assessed with respect to EGFR expression and intensity. |
| Primary End Point: | OS, and correlation study with EGFR expression |
| Secondary End Point: | NA |
| Patients Number: | 92 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Two antibodies, which recognized independent epitopes, were used to assess EGFR expression levels by immunohistochemistry. EGFR detection using mR3, an antibody with similar specificity to Nimotuzumab, correlated significantly with the expression of ErbB3 (p<0.05), PCNA and pMAPK (p<0.001). Although EGFR expression showed a significant relationship to patient survival in patients treated with Nimotuzumab and chemoradiation (p=0.02), pMAPK expression did not (p=0.07). Interestingly, EGFR overexpression (as defined by mR3) correlated directly with overall survival in this group (p=0.01). This data supports a model of basal activation of the EGFR signal transduction pathway in these oropharyngeal tumors. Detection of EGFR by immunohistochemistry could define a subset of treatment na ve Head and Neck cancer patients who may benefit from receiving EGFR targeted therapies in combination with chemoradiation. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | This data supports a model of basal activation of the EGFR signal transduction pathway in these oropharyngeal tumors. Detection of EGFR by immunohistochemistry could define a subset of treatment na?ve Head and Neck cancer patients who may benefit from receiving EGFR targeted therapies in combination with chemoradiation. |