A second randomized clinical trial has confirmed what the first one found — adding Avastin to standard chemotherapy does not reduce recurrences after surgery for stage III colon cancer.
The AVANT trial compared standard FOLFOX chemotherapy to either FOLFOX plus Avastin® (bevacizumab) or XELOX plus Avastin. Chemo was given for 6 months, and Avastin was added during that time and for another 6 months after chemo ended. Nearly 2,870 stage III patients took part in the study.
Like in the C-08 trial, there was a temporary benefit during the year that patients got Avastin, but it didn’t last. By the end of three years the percentage of people who were alive and cancer-free was slightly less in the two Avastin arms.
At three years, disease-free survival was:
- 76% in the FOLFOX only arm
- 73% in the FOLFOX plus Avastin arm
- 75% in the XELOX plus Avastin arm
FOLFOX chemotherapy combines oxaliplatin with leucovorin and continuous infusion 5-FU. XELOX combines oral Xeloda® (capecitabine) with oxaliplatin.
Although it is too early to be certain, there was a trend toward poorer survival in those patients who got Avastin with their chemotherapy.
It is not clear why this might be. There was no serious addition toxicity due to Avastin, When cancer came back, the sites of recurrence weren’t different among the three arms, with most initially in the liver, leading researchers to believe that there wasn’t a “rebound” after Avastin was stopped.
AVANT included collecting tissue and studying a number of biomarkers to see if there might be some subgroups where adding Avastin to chemo might be beneficial. Those results are not yet complete.
In presenting the trial results at the 2011 GI Symposium, Aimery De Gramont, MD, PhD, concluded,
- The addition of bevacizumab to FOLFOX4 or XELOX did not improve disease-free survival in the adjuvant treatment of Stage III colon cancer.
- Immature overall survival data suggest a potential detriment. Continued follow-up is ongoing.
- Bevacizumab treatment effect was not constant over time.
- In the first year, there was a transient favorable effect, consistent with what was found in C-08.
- The treatment effect became unfavorable after one year, which is different than what C-08 discovered. In C-08 there was no difference between arms after one year.
- Bevacizumab is the third agent, after irinotecan and cetuximab, with proven efficacy in metastatic colorectal cancer and no observed benefit in the adjuvant treatment of colon cancer.
SOURCE: De Gramont et al., AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer, 2011 GI Cancers Symposium, Abstract 362.