ASCO GI: Modest Gain With Avastin for Advanced Colorectal Cancer

ORLANDO, Jan. 22 -- Avastin (bevacizumab) added to Eloxatin (oxaliplatin)-based chemotherapy modestly extended progression-free survival in metastatic colorectal cancer, according to results of a randomized phase III trial.

But the improvement, although statistically significant (P=0.0023), only added a little over a month to progression-free survival, which was about 9.4 months, said Leonard Saltz, M.D., of the Memorial Sloan-Kettering Cancer Center in New York, at a gastrointestinal cancers symposium here.

The benefit, said Dr. Saltz, was "more modest than we expected."

"Although previous studies have not examined its use in the first-line setting, oxaliplatin-based chemotherapy plus bevacizumab is nonetheless currently a widely used first-line treatment regimen in standard practice in the United States for advanced colorectal cancer," said Dr. Saltz.

The modest benefit notwithstanding, he added, "it shows that doctors who have been adding Avastin have been doing the right thing in treating patients."

In addition to a less than robust improvement in progression-free survival, Dr. Saltz said, it was also disappointing to learn that "the inclusion of Avastin did not improve the response rate in these patients."

Another finding of the trial, and one that has the potential for greater clinical impact than the Avastin benefit, was the observation that the XELOX chemotherapy regimen, which combined Xeloda (capecitabine) and Eloxatin, was as effective as the standard FOLFOX4 regimen, which contains 5FU (5 fluorouracil), Wellcovorin (leucovorin), and Eloxatin.

"We found that the XELOX regimen resulted in progression-free survival that was basically the same as treatment with the FOLFOX4," he said.

Based on that finding, he added, "we think that XELOX is an acceptable alternative to FOLFOX and because XELOX included Xeloda which is an oral medication we believe that it should be offered to patients who are likely to be compliant with a complicated oral regimen."

Neal Meropol, M.D., of the Fox Chase Cancer Center in Philadelphia, commented that the results confirm that "Xeloda plus Eloxatin is an acceptable backbone of frontline treatment based on these results showing that the XELOX arm is equivalent to FOLFOX arm."

He also agreed that the "study validates the use of Avastin as a component of frontline therapy with Eloxatin-based chemotherapy for metastatic breast cancer."

Dr. Meropol, who was not involved in the study, chaired a press conference where the results of phase III trial were discussed.

The multicenter trial enrolled 1,401 patients who were receiving chemotherapy with either FOLFOX4 or XELOX regimens. The patients were randomized to regimen plus Avastin or placebo.

The complicated trial was designed to compare XELOX to FOLFOX4 in a non-inferiority trail that enrolled 317 patients in each arm from June 2003 to May 2004.

The trial was expanded in February 2004 to include the Avastin versus placebo arms.

That added 350 patients who received XELOX plus placebo, 350 Avastin plus XELOX, 351 who received FOLFOX4 plus placebo, and 349 randomized to FOLFOX4 plus Avastin.

Irrespective of chemotherapy regimen, the median progression-free survival for patients randomized to Avastin was 9.4 months versus eight months for the placebo groups.

Dr. Meropol reported that he acted as a consultant or adviser to Amgen, Genomic Health, Genentech, Pfizer, Bristol-Myers Squibb, and also received research funding from Amgen and Genentech.

The American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, the American Gastroenterological Association Institute, and the Society of Surgical Oncology, jointly sponsored the Gastrointestinal Cancer Symposium.