In advanced colorectal cancer, continuing bevacizumab (Avastin) without interruption after tumor progression improves survival modestly, clinical trial results showed.

Continuous use of the monoclonal antibody improved the odds of overall survival 19%, for a median 1.4 month advantage over a strategy of chemotherapy alone after progression (P=0.0062), Dirk Arnold, MD, of the University Cancer Center in Hamburg, Germany, and colleagues found.

Progression-free survival (PFS) also came out slightly ahead with no break in bevacizumab, the group reported here at the American Society of Clinical Oncology meeting.

These findings are the first prospective confirmation in colorectal cancer of the strategy many clinicians are already using based on observational and preclinical results, Arnold explained at an ASCO press conference.

“These findings indicate a potential new model for treatment approaches through multiple lines in metastatic colorectal cancer and across other tumor types,” he said. The phase III trial included 820 patients whose metastatic colorectal cancer progressed while on a regimen of bevacizumab and standard first-line oxaliplatin (Eloxatin) or irinotecan (Camptosar)-based chemotherapy. For second-line therapy, patients were switched to the other of the two chemotherapy regimens with randomization to take it alone or with continued bevacizumab. Overall survival after progression improved with bevacizumab to a median of 11.2 months compared with 9.8 on chemotherapy alone. While a small difference, the hazard ratio (HR) of 0.81 for death was statistically significant at P=0.0062. The same was true for PFS. The combination of bevacizumab and chemotherapy in second-line was associated with an HR of 0.68 for progression or death (P<0.0001). Median PFS was 5.7 and 4.1 months, respectively. Continuing bevacizumab after the first progression with metastatic cancer didn't appear to add significantly to toxicity. The biggest difference in the rate of serious adverse events was in neutropenia, where the rate was 16% with the combination of treatments compared with 13% on chemotherapy alone. "This provides a new treatment option in second line for patients who have been treated with bevacizumab plus standard chemotherapy in first line while maintaining an acceptable safety profile," the group concluded. The same strategy is commonly used to treat breast cancer despite little clinical trial data, noted Kathy S. Albain, MD, of Loyola University in Chicago, in an interview with MedPage Today. "There's always been concern that when we stop these VEGF [vascular endothelial growth factor] drugs, especially bevacizumab, there may be some rebound going on," she said. "With all these agents we need an answer to the question of whether to stop the targeted drug at the time of progression or continue and add a different agent to it." One study in HER2-positive metastatic breast cancer showed better PFS outcomes when trastuzumab (Herceptin) was started with chemotherapy rather than delaying it until afterward. A second showed an advantage to trastuzumab plus lapatinib (Tykerb) rather than stopping trastuzumab and giving lapatinib alone. The speculation is that this actually reflected a trastuzumab withdrawal effect in the chemotherapy-alone arm, commented Kimberly Blackwell, MD, of Duke University Medical Center, who was lead author on that trial. "I tend to continue the drug for life," she said. Albain added that the downside to these kinds of treatment strategies is that they are costly.