| General information |
| Database: | DB00725 |
| Objective: | Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2; also known as ERBB2), was investigated in combination with chemotherapy for firstline treatment of human epidermal growth factor receptor 2positive advanced gastric or gastrooesophageal junction cancer. |
| Authors: | Bang YJ, et al |
| Title: | Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of human epidermal growth factor receptor 2positive advanced gastric or gastrooesophageal junction cancer (ToGA): a phase 3, openlabel, randomised controlled trial. |
| Journal: | Lancet. |
| Year: | 2010 |
| PMID: | 20728210 |
| Trial Design |
| Clinical Trial Id: | NCT01041404 |
| Agent: | trastuzumab
|
| Target: | Receptor proteintyrosine kinase erbB2
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced adenocarcinoma of the stomach or gastroesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Trastuzumab + chemotherapy |
| Study Type: | a randomised, openlabel, multicentre, international, phase III, randomised controlled trial |
| Key Patients Feature: | Men or women older than18 years of age were eligible for inclusion if they hadhistologically confi rmed inoperable locally advanced, recurrent, or metastatic adenocarcinoma of the stomachor gastrooesophageal junction; Eastern CooperativeOncology Group (ECOG) performance status 0-2;adequate organ function; and measurable or nonmeasurable disease. Tumours were centrally tested forhuman epidermal growth factor receptor 2 status with immunohistochemistry (HercepTest, Dako, Denmark]) and fl uorescence insitu hybridisation(FISH; human epidermal growth factor receptor 2 FISH pharmDx, Dako). Because of theinherent biological diff erences between breast andgastric tumours, notably tumour heterogeneity and theoccurrence of baso(lateral) membrane staining, a newset of immunohistochemistry scoring criteria weredeveloped that are specifi c for gastric cancer. Thesescoring criteria were modifi ed on the basis of the studyby Hofmann and colleagues, 10 and are described intable 1. patients were eligible if their tumour sampleswere scored as 3+ on immunohistochemistry or if theywere FISH positive (human epidermal growth factor receptor 2:CEP17 ratio more than and equal to 2) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Trastuzumab in combination with chemotherapy VS chemotherapy alone |
| Treatment Info: | Participants were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab. |
| Primary End Point: | overall survival in all randomised patients who received study medication at least once. |
| Secondary End Point: | NA |
| Patients Number: | 594 |
| Trial Results |
| DLT_MTD: | The most common adverse events in both groups were nausea (trastuzumab pluschemotherapy, 197 [67%] vs chemotherapy alone, 184 [63%]), vomiting (147 [50%] vs 134 [46%]), and neutropenia(157 [53%] vs 165 [57%]). Rates of overall grade 3 or 4 adverse events (201 [68%] vs 198 [68%]) and cardiac adverseevents (17 [6%] vs 18 [6%]) did not diff er between groups. |
| Objective Response Rate: | Median followupwas 18.6 months (IQR 11-25) in the trastuzumab plus chemotherapy group and 17.1 months (9-25) in thechemotherapy alone group. Median overall survival was 13.8 months (95% CI 12-16) in those assigned to trastuzumabplus chemotherapy compared with 11.1 months (10-13) in those assigned to chemotherapy alone (hazard ratio 0 74;95% CI 0 60-0 91; p=0 0046). |
| Disease Control Rate: | NA |
| Median Time to Progression: | Trastuzumab plus chemotherapy: 7.1 (6-8) months; Chemotherapy alone: 5.6 (5-6) months |
| Median PFS A vs. C: | 6.7 months (95% CI 6-8) in the trastuzumab plus chemotherapy group compared with 5.5 months (5-6) in the chemotherapy alone group (HR 0.71, 95% CI 0.59-0.85; p=0.0002) |
| Median OS A vs. C: | 13.8 months (95% CI 12-16) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months (10-13) in those assigned to chemotherapy alone (hazard ratio 0 74; 95% CI 0 60-0 91; p=0 0046). |
| Adverse Event(agent arm): | The most common adverse events in both groups were nausea (trastuzumab plus chemotherapy, 197 [67%] vs chemotherapy alone, 184 [63%]), vomiting (147 [50%] vs 134 [46%]), and neutropenia (157 [53%] vs 165 [57%]). Rates of overall grade 3 or 4 adverse events (201 [68%] vs 198 [68%]) and cardiac adverse events (17 [6%] vs 18 [6%]) did not diff er between groups. |
| Conclusions: | Trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with human epidermal growth factor receptor 2positive advanced gastric or gastrooesophageal junction cancer. |