| General information |
| Database: | DB00366 |
| Objective: | EGFR overexpression occurs in 2755% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. They aimed to assess addition of the antiEGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. |
| Authors: | Waddell T, et al |
| Title: | Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, openlabelphase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2013 |
| PMID: | 23594787 |
| Trial Design |
| Clinical Trial Id: | NCT00824785 |
| Agent: | panitumumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Epirubicin, oxaliplatin, and capecitabine with or without panitumumab |
| Study Type: | openlabel, multicentre, phase III, randomised controlled trial, |
| Key Patients Feature: | eligible patients hadhistologically verified, untreated, metastatic or locallyadvanced inoperable adenocarcinoma or undifferentiatedcarcinoma of the oesophagus, gastrooesophagealjunction, or stomach. patients were aged at least 18 yearsand had measurable disease on CT or MRI. Othereligibility criteria included WHO performance status of 0-2, and adequate cardiac, renal, liver, and bonemarrow function. Cardiac function was not formallymeasured at baseline unless there were concerns basedon previous medical history. Renal, liver, and bonemarrow function were assessed via routine blood tests(full blood count and biochemistry). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A:panitumumab B:panitumumab+EOC |
| Treatment Info: | Eligible patients were randomly allocated (1:1) to receive up to eight 21day cycles of openlabel EOC (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1250 mg/m(2) per day on days 121) or modifieddose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m(2) and oxaliplatin 100 mg/m(2) on day 1, capecitabine 1000 mg/m(2) per day on days 121, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. |
| Primary End Point: | overall survival |
| Secondary End Point: | NA |
| Patients Number: | 553 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 61 patients who were still on treatment (37 in the EOC group and 24 in the mEOC+P group) and had not reached their first response assessment at the time of data censoring were excluded from the response analysis. Patients who died, progressed, or withdrew before response assessment were classed as nonresponders. 116 (46%) of 254 patients in the mEOC+P group had a complete or partial response compared with 100 (42%) of 238 patients in the EOC group (odds ratio 1.16, 95% CI 0.81-1.66, p=0.42; |
| Disease Control Rate: | 25.5% in the experimental group vs 16.0% in controls, p=0.014 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6.0 months (95% CI 5.5-6.5) in the mEOC+P group and 7.4 months (6.3-8.5 ) in the EOC group. |
| Median OS A vs. C: | patients allocated EOC was 11.3 months (95% CI 9.6-13.0) compared with 8.8 months (7.7-9.8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1.37, 95% CI 1.07-1.76; p=0.013). |
| Adverse Event(agent arm): | mEOC+P was associated with increased incidence of grade 3-4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two [1%]), mucositis (14 [5%] vs none), and hypomagnesaemia (13 [5%] vs none) but reduced incidence of haematological toxicity (grade more than and equal to 3 neutropenia 35 [13%] vs 74 [28%]). |
| Conclusions: | Addition of panitumumab to EOC chemotherapy does not increase overall survival and cannot be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma. |