This international trial, published in The Lancet, is one of the largest phase III trials in second-line treatment of gastric cancer. Standard care for advanced gastric cancer, known as first-line treatment, is based on chemotherapy, but it only offers a median survival of 8 to 10 months.
The trial investigated the use of ramucirumab, an antibody developed to treat solid tumours that targets Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), a key receptor in the angiogenesis process. It showed that ramucirumab effectively inhibits a group of proteins that stimulate angiogenesis, a physiological process whereby new blood vessels are formed from pre-existing vessels, which plays a key part in malignant tumour growth. These proteins induce capillary growth in the tumour, supplying the nutrients that it needs.
The clinical trial was conducted on 355 patients with advanced gastric cancer, 238 of whom received treatment with ramucirumab, while 117 received placebo. All patients also received best supportive care. The ramucirumab treatment group showed improved median survival (5.2 months versus 3.8 months in the other group), better tumour control and a noteworthy reduction in the risk of disease progression or death. After six months of treatment with ramucirumab, patient survival in this group was 40%, while response to standard treatment was notably lower (below 20%).
Dr Josep Tabernero, Head of the Medical Oncology Department at the Vall d´Hebron University Hospital, Director of the Vall d´Hebron Institute of Oncology (VHIO), and one of the co-authors of this study, confirmed that "the results of this study are important for several reasons. First, the study revives the idea that inhibition of the angiogenesis process plays an important role in gastric cancer, which can be used to achieve results in these patients. This is important because previous studies with the drug bevacizumab - which inhibits the vascular endothelial growth factor (VEGF) - did not show any significant benefit in this disease. Second, the study results open new avenues for patients with gastric cancer, offering more treatment options. Thirdly, new studies combining ramucirumab with chemotherapy drugs in gastric cancer are making us very optimistic about the outcome of these combinations, because of the synergies between the drugs. This is likely to change the way we treat gastric cancer in the future."
A very aggressive cancer
Gastric cancer is the fourth most common cancer worldwide, and the second leading cause of cancer-related death. In Western countries, most patients with gastric adenocarcinoma have advanced disease at diagnosis, and treatment options are limited.
Following first-line gastric cancer chemotherapy, with a median survival of 8 to 10 months, most national medicines agencies have approved second-line treatment in patients with gastric cancer. However, we still need specific new systemic agents, based on our underlying understanding of gastric cancer biology, to improve outcomes in patients with advanced disease. This study opens a new avenue in second-line treatment of this type of cancer.