Ramucirumab prolongs the survival of advance gastric cancer patients

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According to the results of a large multicenter clinical trial led by scientists at the Dana Faber Cancer Research Center, after standard treatment fails, a targeted therapeutic drug can reduce the amount of blood flowing to the tumor, thereby prolonging the survival time of patients with advanced gastric cancer.

In a randomized, controlled phase III clinical trial published in The Lancet, researchers reported that patients who received the antibody drug ramucirumab experienced a long delay before cancer progressed compared to patients in the placebo group.

Because of the selective effect of this antibody, patients receiving ramucirumab usually have moderate side effects, although these patients have a slightly increased incidence of hypertension compared to patients in the control group.

Dana Fabre cancer researcher and first author of the REGARD clinical trial report Charles Fuchs, M.D .; Master of Public Health said: “It is very impressive that this antibody has minimal side effects, but it can provide more obvious Benefit from survival. ”

This clinical trial enrolled 355 patients with gastric cancer or gastroesophageal junction cancer. These patients were treated at 119 medical centers in 29 countries.

Worldwide, gastric cancer ranks second among cancer-related deaths, but the burden of gastric cancer in the United States is much less. In 2013, an estimated 21,600 new cases and 10.990 deaths were reported. The usual treatment for advanced gastric cancer is chemotherapy, but if the cancer continues to progress, there is currently no approved second-line treatment.

“We realize that we need better treatments for gastric cancer, because for the most part, the current paradigm of using conventional chemotherapy is far from enough,” said Fuchs, director of the Gastrointestinal Oncology Department at Dana-Farber Cancer Center. “We need to develop targeted therapeutic drugs to treat this disease, which requires us to really understand and pay attention to the biological process of the disease.”

Rather than want standard toxic chemotherapeutic drugs to kill or prevent cancer cells from dividing, ramucirumab targets protein signals in the circulation that trigger new blood vessel formation to support tumor growth and spread. Ramucirumab is designed to reduce the formation of new blood vessels (angiogenesis) by blocking the VEGF receptor-2 (VEGFR-2) signaling pathway, so that the tumor can not get nutrients and starve to death. Blocking VEGFR-2 in animal models can slow the growth of gastric cancer in mice.

In the clinical trial of ramucirumab, 355 patients with advanced gastric cancer received antibody drugs plus optimal support therapy every two weeks, while another 117 patients received placebo plus optimal support therapy.

The study was completed in July 2012, and analysis revealed that the use of ramucirumab can significantly reduce the mortality rate by 22%. In addition, the median overall survival time in patients treated with ramucirumab arm was 5.2 months, compared with 3.8 months in the placebo group. The drug delayed cancer progression by 53%. In patients receiving ramucirumab, the rate of cancer progression at 12 weeks was 40%, compared with 16% in the placebo group. The researchers considered that with ramucirumab, gastric cancer was controlled at a median time of 4.2 months, compared to only 2.9 months for the placebo group.

“Our finding is that patients receiving this antibody treatment can significantly increase their survival time while significantly reducing the rate of cancer progression,” Fuchs said. “This result is encouraging, and we hope that this drug will eventually be approved and used as a routine treatment for patients with gastric cancer.” He added that clinical trials are underway to find out whether ramucirumab can be added to the combination of chemotherapy treatment Use “for better healing results.”

Side effects are relatively common in both groups, and the incidence of serious side effects is comparable. However, the incidence of hypertension in patients in the ramucirumab group was 7.6%, compared with 2.6% in the placebo group. According to research reports, the drug has not observed some side effects caused by previous anti-vascular survival drugs, such as increased bleeding thrombosis, gastrointestinal perforation, etc.

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