| General information |
| Database: | DB00440 |
| Objective: | The efficacy of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib was assessed in a phase II study in patients with advanced esophageal cancer. Several biologic features were investigated as potential markers of gefitinib activity. |
| Authors: | Janmaat ML, et al |
| Title: | Predictive factors for outcome in a phase II study of gefitinib in secondline treatment of advanced esophageal cancer patients. |
| Journal: | J Clin Oncol. |
| Year: | 2006 |
| PMID: | 16575012 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophageal cancer |
| Cancer Subtype: | carcinomas of the esophagus |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase II study |
| Key Patients Feature: | Entry criteria included histologically confirmed carcinomas of the esophagus, WHO performance status of 2 o rless, and measurable or assessable disease.Patients with cancers of the gastroesophageal junction were included if more than 50% of the tumor was localized in the esophagus. Patients had to have experienced relapse after one chemotherapy regimen, administered at least 4 weeks before, and have WBC count of more than 4, 000/ L, platele tcount of more than 100, 000/ L, serum creatinine within 1.5 the upper normal limit, and transaminases up to 5 the upper normal limit in case of liver metastases. Patients had to be greater than 18 years old, and life expectancy was to be 12 weeks or longer. Excluded were patients who received prior treatment with an EGFR inhibitor; patients with brain metastases, with unresolved toxicities from prior treatment, or with other active malignancies in the last 5 years; female patients who were pregnant or breast feeding; and patient susing concomitant liver enzyme-inducing medicines (eg, phenobarbital, phenytoin). |
| Biomarker: | gene mutations in EGFR, kras, and PIK3CA; protein expression levels of EGFR, pAkt, and pErk; and EGFR gene amplification |
| Biomark Analysis: | Although EGFR or PIK3CA mutations were absent, kras mutations were found in two patients with progressive disease. High EGFR gene copy number was identified in two patients experiencing partial response or progressive disease. A higher disease control rate (response plus stable disease) was observed in females (P = .038) and in patients with squamous cell carcinoma (SCC; P = .013) or high EGFR expression (P = .002). |
| Control Group Info: | single arm |
| Treatment Info: | Patients with advanced esophageal cancer, who had failed one line of prior chemotherapy, were administered gefitinib 500 mg/d.Response was evaluated every 8 weeks. Tumor material obtained before gefitinib treatment was investigated for gene mutations in EGFR, kras, and PIK3CA; protein expression levels of EGFR, pAkt, and pErk; and EGFR gene amplification. |
| Primary End Point: | tumor response |
| Secondary End Point: | duration of responses and progression free survival, the disease control rate, and the tolerability of the treatment. |
| Patients Number: | 36 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | one (2.8%) achieved a partial response, 10 (27.8%) had stable disease, 17 (47.2%) experienced progression on treatment, and eight (22.2%) were not assessable for response. |
| Disease Control Rate: | 0.306 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 59 days (95% CI, 49 to 80 days) |
| Median OS A vs. C: | 164 days (95% CI, 0 to 333 days) |
| Adverse Event(agent arm): | The most common gefitinibrelated adverse effect was diarrhea (58.3%), follotheyd by rash (47.2%). Severe adverse effects were relatively infrequent, and in general, the treatment was well tolerated. No toxic deaths were reported. |
| Conclusions: | Gefitinib has a modest activity in secondline treatment of advanced esophageal cancer. However, the patient outcome was significantly better in female patients and in patients demonstrating high EGFR expression or SCC histology. The selection of esophageal cancer patients for future studies with EGFRTKIs based on the level of EGFR expression in their tumors or SCC histology should be considered. |