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| |  Adding Trastuzumab to Standard Cisplatin-Based Chemotherapy Provides Benefits for Patients With Advanced Gastric Cancer: Presented at ECCO-ESMO By Chris Berrie BERLIN -- September 30, 2009 – Trastuzumab, in combination with standard cisplatin-based chemotherapy, is well tolerated and provides significant survival benefits over chemotherapy alone for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, researchers stated at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO). “Gastric cancer is a difficult disease to treat, and the median survival with advanced or metastatic gastric cancer is poor, at around 10 or 11 months, when treated with a reference cytotoxic combination,” said principal investigator Eric Van Cutsem, MD, PhD, Gastrointestinal Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium. There is, thus, an unmet need for better treatment options in advanced gastric/gastro-oesophageal junction (GEJ) cancer, he explained during his presentation of a multicentre, randomised, open-label phase 3 trial here on September 24. The main entry criteria for the study were adenocarcinoma of the stomach or GEJ, with inoperable locally advanced disease and/or metastatic disease. Subjects were required to have measurable or evaluable disease, a HER2-positive tumour, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and adequate organ function. In all, 584 patients had advanced gastric cancer, and were randomised to receive 5-fluorouracil or capecitabine plus cisplatin (FC; n = 290) or 5-fluorouracil or capecitabine plus cisplatin plus trastuzumab every 3 weeks for 6 cycles (FCT; n = 294). The main baseline demographics were evenly matched across the FC and FCT arms for median age (59.0 vs 61.0 years); gender (male, 75% vs 77%); type of gastric cancer (about 75% intestinal and 15% mixed); and prior gastrectomy (21.4% vs 24.1%). For the stratification factors, Dr. Van Cutsem noted the main primary tumour site (80% stomach), the ECOG performance status (90% 0/1), and prior capecitabine treatment (almost 90%). The primary endpoint of median overall survival showed significant benefit for the addition of trastuzumab to FC: median overall survival was 11.1 months for the FC group versus 13.8 months for the FCT group (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.60-0.91; P = .0046). Similarly, the secondary endpoint of median progression-free survival was 5.5 months for the FC group versus 6.7 months for the FCT group (HR, 0.71; 95% CI, 0.59-0.85; P = .0002). Further efficacy endpoints included significant benefits for median time to progression; overall response rate; patients with measurable disease; median duration of response; and clinical benefit rate. For the preplanned subgroup efficacy analysis of overall survival by HER2 status, the higher immunohistochemistry (IHC) scores (2+ and 3+ being borderline and positive) correlated with increased trastuzumab efficacy. Indeed, significant further benefit was indicated in the risk ratio with the addition of trastuzumab (HR, 0.65; 95% CI, 0.51-0.83) during an exploratory analysis for IHC2+/ fluorescence in situ hybridisation assay-positive or IHC3+ status. In the safety analysis, there were no differences between the standard FC group and the experimental FCT group for different haematological adverse events, as seen for nonhaematological adverse events. “Trastuzumab in combination with chemotherapy is a reference treatment for patients with HER2-positive gastric and GEJ cancers, and patients with advanced gastric/GEJ cancer should be offered HER2 testing,” noted Dr. Van Cutsem, adding that trastuzumab is the first biological therapy to show survival benefit in gastric/GEJ adenocarcinoma. Funding for this study was provided by Roche. [Presentation title: Trastuzumab Added to Standard Chemotherapy (CT) as First-Line Treatment in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer (GC): Efficacy and Safety Results From the Phase III ToGA Trial. Abstract 7BA]
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