| General information |
| Database: | DB00463 |
| Objective: | Amplification of the MET protooncogene in gastroesophageal cancer (GEC) may constitute a molecular marker for targeted therapy. They examined a GEC cohort with followup and reported the clinical response of four additional patients with METamplified tumors to the small molecule inhibitor crizotinib as part of an expandedphase I cohort study. |
| Authors: | Lennerz JK, et al |
| Title: | MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 22042947 |
| Trial Design |
| Clinical Trial Id: | NCT00585195 |
| Agent: | crizotinib
|
| Target: | Hepatocyte growth factor receptor, ALK, ROS1
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the lower oesophagus, oesophagealjunction or stomach |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | survival analysis |
| Key Patients Feature: | patients with GEC and with biopsyproven carcinoma (all types) seen at Massachusetts General Hospital (MGH) Cancer Center/Dana Farber Harvard Cancer Center |
| Biomarker: | MET, EGFR, and human epidermal growth factor receptor 2 amplification status |
| Biomark Analysis: | Survival analysis in patients with stages III and IV disease showed substantially shorter median survival in MET/EGFRamplified groups, with a rank order for all groups by median survival (from most to least aggressive): MET (7.1 months; P < .001) less than EGFR (11.2 months; P = .16) less than human epidermal growth factor receptor 2 (16.9 months; P = .89) when compared with the negative group (16.2 months). Two of four patients with METamplified tumors treated with crizotinib experienced tumor shrinkage (30% and 16%) and experienced progression after 3.7 and 3.5 months. |
| Control Group Info: | single arm |
| Treatment Info: | patients with GEC were genetically screened as a consecutive series of 489 tumors (stages 0, I, and II, 39%; III, 25%; IV, 36%; n = 222 esophageal, including n = 21 squamous carcinomas). MET, EGFR, and human epidermal growth factor receptor 2 amplification status was assessed by using fluorescence in situ hybridization. |
| Primary End Point: | overall survival |
| Secondary End Point: | NA |
| Patients Number: | 489 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Specifically, both patients had stage IV junctional GEC; after 1 week of crizotinib, patient Cr3 experienced rapid symptomatic response with improvement in appetite, reduction of pain, and improvement in performance status. A computed tomography scan at the end of cycle 2 (8 weeks) showed a partial response to treatment with a 39% reduction in tumor measurements, which was confirmed at 12 weeks (41% reduction) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | patients with stages III and IV disease showed substantially shorter median survival in MET/EGFRamplified groups, with a rank order for all groups by median survival (from most to least aggressive): MET (7.1 months; P .001) less than EGFR (11.2 months; P .16) less than human epidermal growth factor receptor 2 (16.9 months; P .89) when compared with the negative group (16.2 months) |
| Adverse Event(agent arm): | NA |
| Conclusions: | MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib (PF02341066). |