| General information |
| Database: | DB00405 |
| Objective: | a phase II trial of the oral epidermal growth factor receptor (EGFR) inhibitor erlotinib in patients with gastroesophageal adenocarcinomas stratified according to primary tumor location into two groups: gastroesophageal junction (GEJ)/cardia and distal gastric adenocarcinomas. |
| Authors: | Dragovich T, et al |
| Title: | Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. |
| Journal: | J Clin Oncol. |
| Year: | 2006 |
| PMID: | 17050876 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the stomach or gastroesophageal junction |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase II, openlabel, multicenter trial |
| Key Patients Feature: | Patients with a histologic or cytologic diagnosis of adenocarcinoma of the GEJor stomach (ST) and measurable disease by Response Evaluation Criteria inSolid Tumors (RECIST) criteria were considered eligible for the trial. Thepatients were stratified into two groups: GEJ versus gastric (ST) adenocarcinoma. In this study, GEJ tumors included adenocarcinomas arising within 5cm of the anatomic GE junction (distal esophagus) or from gastric cardia.More distally located tumors were recorded as gastric. Only patients withmetastatic or unresectable disease were included. Adjuvant radiation or chemoradiotherapy therapy was allowed, but no prior therapy for metastatic diseasewas permitted. Additional eligibility requirements included performance status on Zubrod scale of 0 to 1, the ability to take and absorb oral medications, and adequate bone marrow and hepatic and renal function. Patients had tohave an absolute neutrophil count of at least 1, 500 per mm3, platelets at least100, 000/mm3, serum creatinine 2 upper limit of normal or lotheyr and bilirubin 1.5 upper limit of normal or lotheyr, and AST and ALT 1.5 upper limitof normal or lotheyr ( 5 upper limit of normal if due to liver metastases). |
| Biomarker: | intratumoral EGFR, transforming growth factoralpha or phosphorylated Akt kinase expression |
| Biomark Analysis: | No somatic mutations of the EGFR exons 18, 19, or 21 were detected and there was no gross amplification of EGFR by fluorescence in situ hybridization. |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated with erlotinib 150 mg/d orally. |
| Primary End Point: | overall response rate. |
| Secondary End Point: | (1) assessment of treatment related toxicity; (2) determination of the overall survival and time to treatment failure (TTF); and (3) exploratory analyses of biologic markers and the EGFR signaling pathway in patient samples. |
| Patients Number: | 70 |
| Trial Results |
| DLT_MTD: | In a phase I study, the maximumtolerated dose wasachieved at 150 mg daily dose of erlotinib administered continuously |
| Objective Response Rate: | There were no objective responses in the gastric arm In the GEJ stratum, there was one complete response and three confirmed partialresponses, with an objective response rate of9%(95%CI, 3%to 22%).There was another unconfirmed partial response in the GEJ stratum(12% unconfirmed response rate) |
| Disease Control Rate: | 23.25% in GEJ Arm; 4% in Gastric Arm |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 6.7 months in GEJ and 3.5 months in ST stratum. |
| Adverse Event(agent arm): | Percentage of common toxicities were skin rash, 86% and 72%; fatigue, 51% and 44%; and AST/ALT elevation, 28% and 28%, respectively for GEJ and ST. |
| Conclusions: | Erlotinib is active in patients with GEJ adenocarcinomas, but appears inactive in gastric cancers. The molecular correlates examined were not predictive of the patient therapeutic response. |