Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)
Mené sur 262 patients atteints d'un cancer colorectal métastatique, cet essai de phase III évalue l'efficacité, du point de vue du délai avant progression, de l'interruption du traitement par bevacizumab après la fin d'une chimiothérapie de première ligne en combinaison avec du bevacizumab
Background : Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. Patients and methods : In an open-label, phase III multicentre trial, patients with metastatic colorectal cancer without disease progression after 4–6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary endpoint was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. Results : The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. Median TTP was 4.1 months (95% CI 3.1–5.4 months) for bevacizumab continuation versus 2.9 months (95% CI 2.8–3.8 months) for no continuation; HR 0.74 (95% CI 0.58–0.96). Non-inferiority could not be demonstrated. Median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63–1.1; p=0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be approximately 30,000 USD per patient. Conclusions : Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy.
Annals of Oncology 2015