Elsevier

Annals of Oncology

Volume 26, Issue 4, April 2015, Pages 709-714
Annals of Oncology

original articles
gastrointestinal tumors
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)

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ABSTRACT

In this trial, stopping bevacizumab after completion of induction chemotherapy was associated with a shorter time to progression, but no statistically significant difference in overall survival compared with the bevacizumab continuation strategy. Non-inferiority could not be demonstrated. Treatment costs are substantially higher for continuous bevacizumab treatment.

Background

Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) 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 mCRC 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 end point 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. The median TTP was 4.1 [95% confidence interval (CI) 3.1–5.4] months for bevacizumab continuation versus 2.9 (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. The 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 ∼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.

Clinical trial registration

ClinicalTrials.gov, number NCT00544700.

metastatic colorectal cancer
bevacizumab
maintenance therapy

Cited by (0)

Present address: Department of Oncology, St Claraspital, Basel, Switzerland.