Source: Kardiologiia  |  Posted 8 years ago

By Roberta Friedman, PhD

SAN FRANCISCO, CA -- January 26, 2004 -- The new standard chemotherapy for advanced colorectal cancer is boosted by adding bevacizumab, and the combination is safe, according to Phase III data on 925 patients presented here January 24th at the First Annual Gastrointestinal Cancers Symposium, a meeting sponsored jointly by the American Society of Clinical Oncology and other societies.

The study had enrolled three arms, including one with the prior standard chemotherapy 5-fluorouracil (5-FU) and leucovorin and one with the new standard, irinotecan, 5-FU, and leucovorin (IFL). Safety of adding the antibody bevacizumab to the IFL treatment was assured by an interim analysis. Since the new combination was proving safe, the investigators stopped enrolling patients in the study arm with the old chemotherapy lacking irinotecan.

Bevacizumab was given at 5 mg/kg every 2 weeks.

Analysis of that dropped arm, with 100 patients, was presented at the meeting. These patients had improved rates of objective response, duration of response, and acceptable toxicities, as did the patients who got antibody combined with IFL.

In comparing the 100 patients in each arm at the time of the third arm's discontinuation, median survival was 20.5 months and 18.3 months, for the IFL group and the group treated with 5-FU and leucovorin plus bevacizumab, respectively, compared to 15.1 months for patients on IFL alone.

Progression free survival was 10.9 and 8.8 months, compared to 6.7 months, for these three groups respectively.

Investigator Herbert Hurwitz, Duke University, Durham, North Carolina, said the antibody is an appreciable addition to the arsenal aimed at colorectal cancer, and has acceptable toxicity.

Dr. Hurwitz said that bleeding in the trial was primarily epistaxis. Half of the six patients who experienced bowel perforation - that might be attributable to the antibody - recovered and continued treatment. Hypertension was another toxicity linked to the antibody, which blocks vascular endothelial growth factor.

Findings are from the same trial presented last June at the ASCO annual meeting, and were part of the submission for approval of bevacizumab by U.S. Food and Drug Administration (FDA).

Subgroup analysis of the Phase III date was also reported at this meeting. Hazard ratio for death remained below 1.0 for adding bevacizumab, compared to chemotherapy alone, for each risk factor that the study pre-selected: poor performance status, advanced age, and site of cancer.

Dr. Hurwitz said the across-the-board efficacy of the antibody for all subgroups speaks to its worth as a helpful addition to chemotherapy for colorectal cancer. He said the FDA is reviewing the data for approval for the new antibody treatment.

Genentech funded the study.

[Study titles: Bevacizumab in combination with 5-fluorouracil and leucovorin: A promising regimen for first-line metastatic colorectal cancer. Abstract OP286; Bevacizumab demonstrated a survival benefit in all pre-specified patient subgroups. Abstract OP223]