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31-05-2012 | Gastroenterology | Article

Poor results for panitumumab in REAL3

Abstract

Meeting website

MedWire News: American Society of Clinical Oncology (ASCO) Annual Meeting; Chicago, IL, USA: 1-5 June, 2012. Addition of the anti-epidermal growth factor receptor (EGFR) antibody panitumumab to a regimen of epirubicin, oxaliplatin, and capecitabine (EOC) for treatment of advanced esophagogastric cancer results in reduced overall survival compared with EOC treatment alone, show findings from the REAL3 trial.Between 27% and 50% of esophagogastric adenocarcinomas overexpress the EGFR protein, which correlates with a poor prognosis for patients.Tom Waddell (Royal Marsden Hospital NHS Foundation Trust, London, UK) and colleagues therefore investigated whether adding panitumumab to EOC, which was found to result in greater survival than a regimen of epirubicin, cisplatin, and fluorouracil (ECF) in the REAL2 trial, would improve outcomes in untreated patients with advanced or metastatic esophagogastric cancer, aged 62 years on average, with unknown EGFR tumor status.The REAL3 trial randomly assigned 275 patients to treatment with EOC (E, 50 mg/m2 on day 1; O, 130 mg/m2 on day 1; and C, 1250 mg/m2 per day on days 1-21) and 278 patients to treatment with modified EOC (E, 50 mg/m2 on day 1; O, 100 mg/m2 on day 1; and C, 1000 mg/m2 per day on days 1-21) plus panitumumab (P; 9 mg/kg on day 1).The EOC and EOC+P patients were followed up for a median of 5.0 and 5.2 months, respectively. The primary endpoint was overall survival, with progression-free survival, response rate, toxicity, and biomarker evaluation also assessed as secondary endpoints.Owing to a significantly reduced overall survival rate in the EOC+P arm, the trial was stopped prematurely after an annual independent data review in October 2011 revealed a 53% increased mortality in the EOC+P versus the EOC group (p=0.006). At this point, all patients in the EOC+P arm were transferred to the EOC arm of the study.Waddell reported results from an updated analysis showing that median overall survival was 8.8 months in the EOC+P group compared with 11.3 months in the EOC alone group (hazard ratio [HR]=1.37; p=0.013).A non-significant trend towards shorter progression-free survival was also observed in the EOC+P group versus the EOC group, at 6.0 versus 7.4 months (HR=1.22; p=0.068).Response rates were similar between the two groups. The overall incidence of grade 3 or higher adverse events was also similar between the two treatment groups, but the EOC+P group did have a significantly higher rate of grade 3/4 diarrhea (17.3% vs 11.1%), skin rash (10.3% vs 0.7%), and mucositis (5.1% vs 0.0%) compared with the EOC group, as well as a lower rate of peripheral neuropathy (1.1% vs 6.7%).Skin rash proved to be a good biomarker of survival in patients treated with EOC+P, as 77% of patients with a grade 1-3 rash on treatment with EOC+P had significantly increased overall survival compared with those that did not (10.2 vs 4.3 months).KRAS and PIK3CA mutations, by contrast, seemed to be associated with reduced overall survival in patients treated with EOC+P, but Waddell noted that only a small number of patients were tested and, as a result, this relationship cannot be confirmed."The addition of panitumumab to EOC was not beneficial in an unselected esophagogastric cancer population," commented Waddell.He went on to suggest that "the poor overall survival outcome is possibly, in part, due to reduced chemotherapy delivery in the experimental arm."MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Helen Albert

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