According to a new phase 2 trial published Online First in The Lancet Oncology, the combination of the widely used anti-cancer drug bevacizumab with standard chemo-radiation therapy is safe, and could prolong survival in patients with advanced nasopharyngeal carcinoma, without any apparent increased adverse side effects.

The results of the RTOG 0615 trial, conducted by the Radiation Therapy Oncology Group (RTOG), suggest that bevacizumab might be more effective at preventing the spread of nasopharyngeal carcinoma to other parts of the body. Spreading of the disease is the most common cause of mortality in patients with advanced nasopharyngeal carcinoma.

Lead Investigator Nancy Lee, MD, from the Memorial Sloan-Kettering Cancer Center in New York and her team reported that over 90% of patients treated with the new combination therapy survived for 2 years with no distant metastases and that the disease did not progress in 75% of patients.

They discovered that treatment with bevacizumab increased patients’ overall chances of survival for 2 years or more compared with findings from earlier studies of chemo-radiation alone. They reported that at 2 years, an “unexpectedly high” number of 91% of patients were still alive.

Joseph Wee, from the National Cancer Center and Duke-NUS Graduate Medical School in Singapore explains in an accompanying comment:

“[The trial]…resulted in a 2-year distant metastases-free survival rate of about 90%, which seems to be an improvement compared with the expected figure of 70-80%.”

Cancer cells

He continued saying that these findings are indeed promising and provide new hope to those suffering from nasopharyneal carcinoma.

By treating nasopharyneal carcinoma patients with intensity-modulated radiotherapy (IMRT), the researchers observed local tumor control rates of more than 90%, but the disease has the highest rate of developing metastases amongst head and neck cancers, and in about 30% of patients the cancer spreads to distant organs or lymph nodes within 4 to 5 years.

Bevacizumab, a monoclonal antibody that inhibits the vascular endothelial growth factor (VEGF-A), is linked to poor prognosis in head and neck cancers, and is over-expressed in around two-thirds of patients with nasopharyneal carcinoma. The drug has demonstrated a reduction in the rate of distant metastasis and improves disease-free survival in several types of advanced cancer, such as breast cancer, renal cell cancer, colorectal cancer and non-small cell lung cancer.

The study, funded by grants to the Radiation Therapy Oncology Group from the US National Cancer Institute, was conducted on 46 patients with loco-regionally advanced nasopharyneal carcinoma who were previously untreated. The participants came from 19 RTOG member centers in North America and Hong Kong and received Bevacizumab parallel and in addition to chemotherapy phases with cisplatin and fluorouracil.

The findings showed that the bevacizumab therapy was well tolerated, with no observed grade 3 to 4 bleeding or grade 5 adverse events. Nine patients (20%) experienced grade 1 to 2 bleeding, with the most common grade 3 or higher adverse events consisting of complications linked to blood or bone marrow (36%) and 77% of patients suffering from acute mucositis, a painful inflammation of mucous membranes in the mouth.

The researchers conclude:

“The addition of bevacizumab to chemo-radiation for nasopharyneal carcinoma is feasible in that it causes no major compromise in the delivery of standard chemo-radiation…and might delay the progression of sub-clinical disease. Although the addition of bevacizumab did not seem to result in any unusual grade 3-4 events, toxicity was still substantial and compliance to protocol treatment was not ideal…So further research is needed to identify those at risk of distant metastasis and hence those who might benefit most from additional bevacizumab.”