Results from a large, Phase III clinical trial show that combination treatment with bevacizumab and standard chemotherapy in the second line setting in patients with advanced colorectal cancer who have received bevacizumab combination treatment first-line extends overall survival.

These findings validate the treatment that many U.S. oncologists already provide, and they will likely alter the standard of care in Europe and elsewhere where use of bevacizumab is generally restricted to either first- or second-line treatment.

“These findings confirm what many physicians and researchers have long suspected – that extended bevacizumab treatment provides meaningful benefits for patients with advanced colorectal cancer, without adding significant side effects,” said Dirk Arnold, MD, Director of the Hubertus Wald Tumor Center, University Cancer Center (UCCH) of University Clinic Eppendorf, Hamburg, Germany, and Speaker of the German AIO Colorectal Cancer Collaborative Study Group (which initiated the trial).

“But the findings also provide an important new insight about the biology of advanced colorectal cancer, showing us that if the disease develops resistence to chemotherapy, it does not necessarily mean that tumours become resistant to anti-angiogenic therapy. By simply switching chemotherapy drugs when the cancer progresses and continuing with bevacizumab, we can make second-line treatment even more powerful. This finding will likely spur research into other cancer types that are sensitive to both bevacizumab and chemotherapy.”

Bevacizumab is known as an anti-angiogenic targeted therapy, meaning it works by blocking the development of blood vessels that tumours need to grow and spread. In the U.S., bevacizumab is already approved for first and/or second-line therapy for advanced colorectal cancer, together with standard oxaliplatin or irinotecan chemotherapy.

These approvals were based on trials evaluating the combination of bevacizumab and chemotherapy in either first- or second-line therapy, not both. This is the first randomised trial to evaluate the combination regimen in second-line in patients who have previously been treated with a bevacizumab regimen in the first-line setting.

In this Phase III randomised trial, 820 patients with metastatic, inoperable colorectal cancer were treated with standard first-line chemotherapy (physician’s choice of oxaliplatin- or irinotecan- based) plus bevacizumab. Following disease progression, patients were randomised to receive the opposite chemotherapy drug plus bevacizumab or placebo. Researchers observed that both overall survival (11.2 months vs. 9.8 months) and progression-free survival were significantly longer (5.7 vs. 4.1 months) among patients who received bevacizumab.

Overall, treatment was well-tolerated by patients in both arms: side effects associated with bevacizumab therapy were comparable with those observed in past studies. 

Source: ASCO