| General information |
| Database: | DB00429 |
| Objective: | REAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that perioperative epirubicin, cisplatin and infused 5fluorouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. |
| Authors: | Okines AF, et al |
| Title: | Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials. |
| Journal: | Eur J Cancer. |
| Year: | 2013 |
| PMID: | 23481512 |
| Trial Design |
| Clinical Trial Id: | NCT00824785 |
| Agent: | panitumumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophageal cancer |
| Cancer Subtype: | esophagogastric cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | EOC+panitumumab(Epirubicin, oxaliplatin, and capecitabine (EOC) is a standard treatment in advanced esophagogastric cancer) |
| Study Type: | analysis of results from the REALIII and TransMAGIC trials |
| Key Patients Feature: | NA |
| Biomarker: | KRAS, BRAF and PIK3CA mutations and PTEN expression |
| Biomark Analysis: | Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%), PIK3CA (2.5%) and loss of PTEN expression (15.0%). Noneof the biomarkers evaluated predicted resistance to mEOC + P. In MAGIC, mutations in KRAS, BRAF and PIK3CA and loss of PTEN (phosphatase and tensin homolog) were found in 6.3%, 1.0%, 5.0% and 10.9%, respectively, and were not associated with survival. |
| Control Group Info: | A: EOC B: EOC+panitumumab |
| Treatment Info: | Analysis of response rate (RR; the primary endpoint ofphase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC + P in REAL3was preplanned to determine if molecular selection for the ongoing study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pretreatment biopsies and results correlated with response to mEOC + P. Association between these biomarkers and overallsurvival (OS) was assessed in MAGIC patients to determine any prognostic effect. |
| Primary End Point: | biomarker analysis |
| Secondary End Point: | NA |
| Patients Number: | 200 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Eleven mEOC + P and 14 EOC patients who withdrew or died prior to radiological (or clinical) assessment of response are analysed as no response. Overall RR in 100 patients randomised to mEOC + P was 52% (95% confidence interval (CI) 42-62%), comprising complete response (CR) in three patients, partial response (PR) in 49, stable disease (SD) in 19 and disease progression (PD) in 18. RR to EOC was 48% (95%CI 38-58%), with CR in 4 patients, PR in 44, SD in 24 and PD in 14. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | The RR of 52% in REAL3 with mEOC+P met predefined criteria to continue accrual tophase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect. |