Bevacizumab's Indication Extended in Colorectal Cancer

Zosia Chustecka

January 24, 2013

Bevacizumab (Avastin, Genentech/Roche) is already approved for use in combination with chemotherapy as a first-line treatment for metastatic colorectal cancer, but the drug now has an extended indication. The US Food and Drug Administration has approved new labeling, which allows the use of bevacizumab to be continued after disease progression. The European product labeling has also been updated.

"The majority of people diagnosed with metastatic colorectal cancer receive [bevacizumab] plus chemotherapy as their initial treatment," said Hal Barron, MD, chief medical officer at Genentech, in a press release. "These people now have the option to continue with [bevacizumab] plus a new chemotherapy after their cancer worsens, which may help them live longer than changing to a new chemotherapy alone," he explained.

The clinical data to support this indication come from the phase 3 ML18147 study, which was presented last year at the annual meeting of the American Society of Clinical Oncology, and reported at the time by Medscape Medical News.

Many oncologists in the United States are already extending bevacizumab beyond first progression; this study gives justification for that, said Bruce J. Roth, MD, professor of medicine in the division of oncology at Washington University School of Medicine in St. Louis, Missouri.

At the meeting last year, Dr. Roth explained that the trial was well designed and demonstrated the benefit of continuation, but didn't address the magnitude of that benefit. "That's...for individual physicians and their patients to decide," he added.

One issue is the high cost of the drug, and the question of "whether it is worth these months of second-line therapy," Dr. Roth said. "It's hard to know where that breakpoint is, but this study provides a scientific benefit for that strategy."

Improved Survival

The ML18147 study involved 820 patients with metastatic colorectal cancer whose disease had progressed after bevacizumab plus standard first-line chemotherapy (fluoropyrimidine plus either irinotecan or oxaliplatin). All patients were then treated with a chemotherapy different than their first-line regimen, and half continued on bevacizumab.

The results, calculated from the initiation of this second-line treatment, show significantly better median overall survival with bevacizumab continuation than with chemotherapy alone (11.2 vs 9.8 months; hazard ratio [HR], 0.81; P = .0057), and significantly better median progression-free survival (5.7 vs 4.1 months; HR, 0.68; P < .0001).