PRIMARY TUMOR LOCATION AND AVASTIN EFFICACY

NEW YORK (Reuters Health) Aug 19 - Bevacizumab appears to be most effective for metastatic colorectal cancer when the primary tumor originates distally, a retrospective Danish study suggests.

"The main message from this hypothesis-generating study is that there may be more benefit from adding bevacizumab to chemotherapy in patients with distal primary tumors," Dr. Mogens Karsboel Boisen from Copenhagen University Hospital in Herlev told Reuters Health by email.

But, Dr. Boisen emphasized, "This hypothesis needs validation in large randomized trials before it can be used for decision-making. This is the first publication to raise this hypothesis regarding bevacizumab. We are currently working with our international collaborators to investigate this hypothesis in data from randomized phase 3 trials."

Presently, there are no prognostic markers to help select patients who are likely to benefit from treatment with bevacizumab, Dr. Boisen and colleagues wrote in a paper online July 17 in Annals of Oncology. They note, however, that expression of VEGF (bevacizumab's target) is higher in tumors from the distal colon than those in the proximal colon.

This prompted Dr. Boisen and colleagues to investigate the impact of the primary tumor location on outcomes in 880 patients with metastatic colorectal cancer (mCRC) treated with first-line capecitabine and oxaliplatin (CAPEOX) with or without bevacizumab.

Among patients who received CAPEOX and bevacizumab, median progression-free survival was significantly higher for patients with tumors arising in the sigmoid colon and rectum (9.3 months) compared to those with tumors originating in the cecum and as far as the descending colon (7.2 months), which translated to a hazard ratio of 0.68.

Corresponding figures for median overall survival were also significantly different at 23.5 versus 13.0 months, respectively (HR 0.47), the team found.

On the other hand, primary tumor location had no effect on survival among patients who received only CAPEOX.

"The addition of bevacizumab to CAPEOX in the first-line treatment of patients with mCRC may primarily benefit patients with primary tumors originating in the rectum and sigmoid colon," Dr. Boisen and colleagues conclude.

Does this mean bevacizumab isn't useful for tumors that originate proximally? "We cannot conclude on this point from our data," Dr. Boisen said, pointing out again that the study was retrospective and exploratory. "Our control group was quite different than our bevacizumab-treated group and this could have influenced our results," he continued. "Most likely, bevacizumab can benefit patients with both types of primary tumors, but maybe it more often or to a larger degree benefits patients with distal primary tumors, which is similar to what we have seen for cetuximab, an anti-EGFR agent."

While Dr. Boisen and his coauthors are careful to acknowledge the limitations of their retrospective study, they also say that "the difference in outcome we observe seems unequivocal and the effect is large, which makes it less likely to be a chance finding."

SOURCE: http://bit.ly/1ePfhIz

Ann Oncol 2013.