| General information |
| Database: | DB00274 |
| Objective: | They sought to evaluate the correlation between tissue biomarker expression (using standardized, quantitative immunofluorescence) and clinical outcome in the E2303 trial. |
| Authors: | Psyrri A, et al |
| Title: | Prognostic biomarkers inphase II trial of cetuximabcontaining induction and chemoradiation in resectable HNSCC: Eastern cooperative oncology group E2303. |
| Journal: | Clin Cancer Res. |
| Year: | 2014 |
| PMID: | 24700741 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | resectable stage III/IV head and neck squamous cell cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | induction chemotherapy with weekly cetuximab, paclitaxel, + carboplatin followed by chemoradiation |
| Study Type: | a phase II trial |
| Key Patients Feature: | eligible patients with operable stage III/IV head and neck squamous cell cancer (HNSCC) |
| Biomarker: | EGF receptor (EGFR), ERK1/2, Met, Akt, STAT3, ¦Âcatenin, Ecadherin, EGFR Variant III, insulinlike growth factor1 receptor, NF¦ÊB, p53, PI3Kp85, PI3Kp110a, PTEN, NRAS, and pRb protein expression levels |
| Biomark Analysis: | Clustering analysis revealed that clusters indicative of activated RAS/MAPK/ERK and/or PI3K/Akt pathways were associated with inferior OS and/or PFS and maintained significance in multivariable analysis. |
| Control Group Info: | single arm |
| Treatment Info: | pts received induction chemotherapy with weekly cetuximab, paclitaxel, and carboplatin followed by chemoradiation with the same regimen. A tissue microarray (TMA) was constructed |
| Primary End Point: | overall survival (OS), progression free survival (PFS), and eventfree survival (EFS) |
| Secondary End Point: | NA |
| Patients Number: | 63 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Tumor extracellular signalregulated kinase (ERK)1/2 levels were significantly associated with PFS [HR (low/high), 3.29; P = 0.026]. ERK1/2 remained significantly associated with PFS (P = 0.022) after controlling for primary site (oropharynx vs. nonoropharynx) and disease stage (III vs. IV). |
| Median OS A vs. C: | Tumor extracellular signalregulated kinase (ERK)1/2 levels were significantly associated with OS [HR (low/high), 4.34; P = 0.008]. ERK1/2 remained significantly associated with OS (P = 0.024) after controlling for primary site (oropharynx vs. nonoropharynx) and disease stage (III vs. IV). Clustering analysis revealed that clusters indicative of activated RAS/MAPK/ERK and/or PI3K/Akt pathways were associated with inferior OS and/or PFS and maintained significance in multivariable analysis. |
| Adverse Event(agent arm): | NA |
| Conclusions: | These results implicate PI3K-Akt and RAS-MAPK-ERK pathways in resistance to cetuximabcontaining chemoradiation in HNSCC. Large prospective studies are required to validate these results. |