| General information |
| Database: | DB00423 |
| Objective: | Esophageal adenocarcinomas commonly express the epidermal growth factor receptor. This trial assessed the 6month overall survival probability in metastatic esophageal cancer patients treated with cetuximab as secondline therapy. |
| Authors: | Gold PJ, et al |
| Title: | Cetuximab as secondline therapy in patients with metastatic esophageal adenocarcinoma: a phase II Souththeyst Oncology Group Study (S0415). |
| Journal: | J Thorac Oncol. |
| Year: | 2010 |
| PMID: | 20631636 |
| Trial Design |
| Clinical Trial Id: | NCT00096031 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the thoracic esophagus orgastroesophageal junction |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase II, openlabel, multicenter trial |
| Key Patients Feature: | 1) a histologic diagnosis of adenocarcinoma of the thoracic esophagus orgastroesophageal junction; 2) measurable disease by Response Evaluation Criteria in SolidTumors (RECIST); 3) one prior regimen of chemotherapy for metastatic or recurrentdisease. Patients may have received one prior regimen of adjuvant or neoadjuvantchemotherapy if administered at the time of initial diagnosis with localized disease. 4) Noprior cetuximab or other therapy targeting the EGF pathway. 5) Patients were required tohave a Zubrod performance status of 0, 1, or 2, and adequate bone marrow, hepatic and renalfunction. Prior radiation and thoracoabdominal surgery were allowed |
| Biomarker: | EGFR, EGF, IL8, COX2, VEGF, CCND1, NRP1 and Kras mutational status |
| Biomark Analysis: | Germline polymorphisms of epidermal growth factor receptor, epidermal growth factor, interleukin (IL)8, cyclooxygenase (COX)2, vascular epidermal growth factor receptor (VEGF), CCND1, neuropilin 1 (NRP1), and Kras mutational status were not associated with response or survival. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received cetuximab 400 mg/m intravenously (IV) on week 1 and 250 mg/m IV weekly thereafter. Tumor tissue was collected for correlative studies. |
| Primary End Point: | 6month overall survival |
| Secondary End Point: | progression free survival, response rate, and toxicity. |
| Patients Number: | 63 |
| Trial Results |
| DLT_MTD: | Two patientsexperienced grade 4 fatigue. Twenty patients experienced grade 3 toxicities, including fourpatients with grade 3 rash. There was one treatmentrelated death due to pneumonitis. Dosereductions or treatment delays were reported for Twentynine of 55 patients (53%). |
| Objective Response Rate: | Twenty patients survived > 6 months for a 6month overall survival rate of 36% (95% CI: 24%, 50%). The median overall survival was 4.0 months (95% CI: 3.2, 5.9). Median progression free survival was 1.8 months (95% CI: 1.7, 1.9). One partial response and 2 unconfirmed partial responses were observed. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.8 months (95% CI: 1.7, 1.9) |
| Median OS A vs. C: | 4.0 months (95% CI: 3.2, 5.9) |
| Adverse Event(agent arm): | Two patients experienced grade 4 fatigue. There was one treatmentrelated death due to pneumonitis. Germline polymorphisms of EGFR, EGF, IL8, COX2, VEGF, CCND1, NRP1 and Kras mutational status were not associated with response or survival. |
| Conclusions: | The 6month overall survival rate of 36% observed on this study failed to meet the primary survival objective. Thus, cetuximab alone cannot be recommended in the secondline treatment of metastatic esophageal cancer. |