| General information |
| Database: | DB00415 |
| Objective: | Cetuximab in combination with irinotecan has shown clinically significant activity in patients with irinotecanrefractory colon cancer. They evaluated the efficacy of cetuximab in combination with cisplatin and irinotecan in patients with metastatic esophagogastric cancer refractory to cisplatin and irinotecan. |
| Authors: | Janjigian YY, et al |
| Title: | Phase II trial of cetuximab plus cisplatin and irinotecan in patients with cisplatin and irinotecanrefractory metastatic esophagogastric cancer. |
| Journal: | Am J Clin Oncol. |
| Year: | 2014 |
| PMID: | 23211227 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | gastric cancer and esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced esophageal, gastroesophageal (GE) junction, gastric adenocarcinoma, orsquamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | cetuximab plus cisplatin and irinotecan |
| Study Type: | Phase II Trial |
| Key Patients Feature: | patients were eligible if they had metastatic esophageal, gastroesophageal (GE) junction, gastric adenocarcinoma, orsquamous cell carcinoma with measurable lesions showingradiographic progressive disease (PD) during treatment withcisplatin/irinotecan. patients were eligible if they had beentreated with cisplatin/irinotecan within 3 months beforeenrollment, and had experienced PD. Other chemotherapyregimens may have been administered between the time ofprogression on prior cisplatin/irinotecan and protocol therapy.A maximum of 2 prior treatment regimens for metastatic disease or as adjuvant/neoadjuvant therapy were permitted.Analysis of tumor tissue for EGFR by IHC was mandated.Both patients with EGFRpositive and EGFRnegative tumors were eligible for enrollment. Other eligibility criteria includedage of 18 years or older, Karnofsky performance statusZ70%, adequate organ and bone marrow function (leukocytesZ3000/mL, absolute neutrophil count Z1500/mL, plateletsZ100, 000/mL, hemoglobin Z9 g/dL, AST and ALT levelsr2.5 upper limit of normal (ULN) or <5 ULN if livermetastases were present, total bilirubin |
| Biomarker: | EGFR Protein Expression |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients with disease progression within 3 months of treatment with prior cisplatin and irinotecan received weekly cetuximab and cisplatin/irinotecan for 2 weeks, followed by a 1week rest period. |
| Primary End Point: | objective response rate |
| Secondary End Point: | progression free and overall survival. |
| Patients Number: | 16 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Most patients (88% each) had esophageal or GE junction primaries and adenocarcinoma histology, respectively. Fifteen patients (94%) had metastatic disease with either the primary tumor in place or locally recurrent disease with distant metastases (1 patient had local recurrence only). The majority of tumors (56%) had high EGFR expression (IHC 2+ or 3+). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.4 months (range, 0.5 to10 months) |
| Median OS A vs. C: | 6 months (range, 0.8 to 26.7 months) |
| Adverse Event(agent arm): | Grade 3/4 toxicities included anemia, fatigue, hypokalemia, hypomagnesemia, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No treatmentrelated deaths occurred. |
| Conclusions: | The addition of cetuximab did not overcome irinotecan resistance in patients with metastatic esophagogastric cancer. Further investigation of this strategy in esophagogastric cancer is not justified. The limited activity observed for cetuximab is consistent with other studies evaluating singleagent cetuximab. |