Antiangiogenesis in Early-Stage Colon Cancer—Microscopically Busted
Mené sur 573 patients atteints d'un cancer du côlon de stade II ayant été réséqué et à haut risque de récidive, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans maladie et de la survie globale, de l'ajout du bévacizumab à une chimiothérapie adjuvante à base d'oxaliplatine (de type FOLFOX ou de type XELOX)
The final report by Chibaudel et al1 on the patients with stage II disease in the large, prospective, randomized phase 3 AVANT (Bevacizumab-Avastin Adjuvant) colon adjuvant therapy trial presents more questions than answers. With only 573 patients randomized to 3 groups, this study is underpowered to show disease-free survival or overall survival benefit for patients with stage II colon cancer. This report1 includes a subset of the larger AVANT trial, and because there are fewer than 200 patients in each group, it only has the power to detect approximately 25% improvement in disease-free survival (which is far more improvement than is possible). Furthermore, the negative results agree with the already reported results from the larger, complete AVANT data set2 and the NSABP (National Surgical Adjuvant Breast and Bowel Project) C-08 study,3 both of which studied the specific role of adjuvant bevacizumab, an antibody directed against vascular endothelial growth factor. We know this antibody essentially binds all free circulating vascular endothelial growth factor and is active in advanced colon cancer and other malignant neoplasms.4 According to the proposed mechanisms of angiogenesis, this drug should work in microscopic disease as tumors activate via the angiogenic switch, which is required to grow from microscopic to macroscopic metastases.5 These events should happen with reasonable frequency over the year of adjuvant antiangiogenic therapy in the experimental groups. Chibaudel et al1 have not provided the same time analysis as provided in the NSABP C-08 study.3 These data showed massive effects during the early months of treatment with bevacizumab (with very positive hazard ratios for recurrence) but then gradual loss of effect over the year of treatment. It would be very interesting to see whether this was also the case for AVANT in both stage II and III cancers.
JAMA Network Open , commentaire, 2019