John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. Stomach cancer is the fifth most common cancer and third leading cause of cancer-related deaths worldwide. Molecular-targeted therapy is one of the newer treatments and a new Cochrane Review in July 2016 looks at the evidence from randomized trials. Lead author, Huan Song from the Karolinska Institutet in Sweden, tells us more in this Evidence Pod.

Huan: Molecular-targeted therapy uses drugs to target specific molecules involved in the growth and spread of cancer cells. Blocking these molecules may kill cancer cells or keep cancer cells from growing or spreading; and because, in theory, the therapy only affect cancer cells, it may cause fewer side effects than other types of cancer treatment. With growing understanding of the underlying molecular basis of carcinogenesis, several targeted agents have been developed, delivering promising outcomes for treating people with lung, colon, breast, and kidney cancer. Clinical trials have also shown some favorable results for stomach cancer generally, even though this type of cancer seems to have a more complicated genetic mechanism for its carcinogenesis. However, the size of any benefit for advanced cancer remains unclear and therefore we did this review to try to tackle this uncertainty.
We investigated whether adding molecular-targeted agents to first-line chemotherapy can improve the survival outcomes for patients with late-stage stomach cancer. We also looked at outcomes such as tumor response rate, quality of life, and adverse events.
We included 11 studies that had randomized a total of just over 4000 patients to molecular-targeted therapy plus conventional chemotherapy or chemotherapy alone. The overall quality of the evidence was low, mainly due to the use of open-label designs in the studies and inconsistencies between the results of individual studies. Combining these findings suggests that molecular-targeted therapy may only have a small effect on mortality and on progression-free survival, compared with conventional chemotherapy alone. We did not find evidence from subgroup analyses that survival outcomes differed by tumor type or the type of molecular-targeted agent, meaning that we were unable to explain the variation in effect across the studies by the presence or absence of particular prognostic biomarkers or use of certain types of molecular-targeted agent.
Based on the low quality evidence, we also found that the addition of molecular-targeted therapy to chemotherapy may increase tumor response by 24%; but the risk of having general or severe adverse events also significantly increased. Furthermore, since quality of life outcomes were only reported in one small trial, we have insufficient data to determine the effect of these therapies on patient’s quality of life.
In summary, our review indicates that the existing trials cannot resolve the uncertainty about whether adding targeted therapy to first-line chemotherapy improves survival outcomes in people with advanced stomach cancer, but the trials do show an increased risk of adverse events, including those regarded as serious. Unfortunately, ongoing studies in this area are small and unlikely to improve our understanding of the effects of targeted therapy, and therefore we think larger trials are really needed.”

John: If you would like to find out more about the closed studies in Huan’s review, the studies that are ongoing, and the more detailed findings of the review, you can find all the details at Cochrane library dot com with a simple search for ‘molecular targeted therapy and gastric cancer’. That’s also how to watch for any updates of the review that are able to take account of any new, larger trials of this topic should those studies be done.

Hello, I'm John Hilton, editor of the Cochrane Editorial unit.