| General information |
| Database: | DB00322 |
| Objective: | Constitutive activation of epidermal growth factor receptor (EGFR) as a result of gene amplification, mutation, or overexpression of its ligands has been associated with response to EGFR targeting strategies. The role of these molecular mechanisms for the responsiveness of squamous cell carcinoma of the head and neck (SCCHN) to cetuximabcontaining regimens remains |
| Authors: | Tinhofer I, et al |
| Title: | Expression of amphiregulin and EGFRvIII affect outcome of patients with squamous cell carcinoma of the head and neck receiving cetuximabdocetaxel treatment. |
| Journal: | Clin Cancer Res. |
| Year: | 2011 |
| PMID: | 21653686 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| 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: | 2 |
| Therapeutic Combination Content: | cetuximab+docetaxel |
| Study Type: | a singlearmphase II multicenterstudy (²¡ÈËÀ´Ô´ÓÚÕâ¸öÑо¿, »Ø¹Ë·ÖÎöµÚµÄ²»ÊÇÁÙ´²Ñо¿) |
| Key Patients Feature: | histologically confirmed recurrent or initially metastatic SCCHN were enrolled in a phaseII multicentric clinical trial for treatment with cetuximaband docetaxel. Further eligibility criteria were tumor relapseafter platinumcontaining chemoradiotherapy or after platinumcontaining firstline chemotherapy, no intermittentanticancer treatment since platinumfailure, ECOG performance status 0-1, adequate bone marrow, liver, and renalfunction, and signed written informed consent. |
| Biomarker: | expression of EGFR, EGFRvIII, and AREG |
| Biomark Analysis: | Expression levels of EGFR had no impact on PFS or OS. High expression levels ofEGFRvIII were significantly associated with reduced DCR and shortened PFS (HR: 3.3, P 0.005) butnot with OS. Patients with high AREG expression in tumor cells had significantly shortened OS (HR: 2.2, P 0.002) and PFS (HR 2.2, P 0.019) compared with patients with low expression score. MultivariateCox analysis revealed an independent association of AREG and EGFRvIII with PFS but only AREG wasan independent prognosticator of OS. |
| Control Group Info: | single arm |
| Treatment Info: | were analyzed by immunohistochemistry for expression of EGFR, its deletion variant III (EGFRvIII) and its ligand amphiregulin (AREG). The relation between expression levels and disease control rate (DCR) was evaluated by logistic regression. Association between expression levels, progression free survival (PFS), and overall survival (OS) was determined by KaplanMeier analysis, logrank test, and uni and multivariate Cox regression analysis. |
| Primary End Point: | The relation between EGFR, EGFRvIII, and AREG immunostaining score and survival |
| Secondary End Point: | NA |
| Patients Number: | 47 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Expression levels of EGFR had no impact on PFS or OS. High expression levels ofEGFRvIII were significantly associated with reduced DCR and shortened PFS (HR: 3.3, P 0.005) butnot with OS. Patients with high AREG expression in tumor cells had significantly shortened OS (HR: 2.2, P 0.002) and PFS (HR 2.2, P 0.019) The overall response rate was 12% and theDCR (PR t SD) 54% |
| Disease Control Rate: | 54%; high AREG IHC score (DCR 40%) as compared with patients with low AREG IHC score (DCR 65%, P 0.09). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | high expression of EGFRvIII had significantly shorter PFS than patients with low expression (logrank, P =0.0028; HR: 3.3; mean PFS, 2.0 vs. 5.4 months); Patients with tumors with high AREG expression had significantly shortened PFS (HR: 2.2, logrank P = .016, mean PFS, 3.1 vs. 5.9 months); |
| Median OS A vs. C: | OS (HR: 2.2, logrank P = 0.0016, mean OS 5.5 vs 9.5 months); Patients with tumors with high AREG expression had significantly shortened OS (HR: 2.2, logrank P =0.0016, mean OS 5.5 vs 9.5 months) compared with patients with low AREG expression score |
| Adverse Event(agent arm): | NA |
| Conclusions: | High EGFRvIII and AREG expression levels identify SCCHN patients who are less likely to benefit from combination treatment with cetuximab and docetaxel. |