Bevacizumab continuation versus no continuation after first-line chemo-bevacizumab therapy in patients with metastatic colorectal cancer: a randomized phase III non- inferiority trial Koeberle D, Betticher D, von Moos R, Dietrich D, Brauchli P, Baertschi D, Matter K, Winterhalder R, Borner M, Anchisi S, Moosmann P, Kollar A, Saletti P, Roth A, Frueh M, Kueng M, Popescu R, Schacher S, Hess V, Herrmann R Swiss Group for Clinical Cancer Reseach
Transcript
Bevacizumab continuation versus no continuation after first-line
chemo-bevacizumab therapy in patients with metastatic colorectal cancer:
a randomized phase III non-inferiority trial
Koeberle D, Betticher D, von Moos R, Dietrich D, Brauchli P, Baertschi D, Matter K, Winterhalder R, Borner M, Anchisi S, Moosmann P, Kollar A, Saletti P, Roth A, Frueh M, Kueng M, Popescu R, Schacher S, Hess V, Herrmann R
Swiss Group for Clinical Cancer Reseach
Background
• Chemotherapy plus Bevacizumab (BEV) is a standard option for first-line treatment in patients with metastatic colorectal cancer
• In many countries duration of first line chemotherapy in the absence of disease progression or severe toxicity is usually limited to 4-6 months
• After stopping first-line chemotherapy plus BEV the value of BEV monotherapy as maintenance strategy until disease progression is unknown
Study design
First-line chemo-therapy + BEVfor 4-6 months
No PDNo PD
Randomization1: 1
BEV continuation(7.5 mg/kg q 3 w)
until PD
No antitumor treatment(no BEV) until PDStratification factors:
• Best response during first-line chemotherapy + BEV (CR/PR vs SD)• Duration of first-line chemotherapy + BEV (16-20 vs 21-24 weeks)• Type of chemotherapy (Irinotecan + 5-FU vs Oxalipaltin + 5-FU vs Fluoropyrimidine mono)• Disease burden (metastases in one organ vs multiple organs)• Center
Study conducted in 26 sites in Switzerland (accrual period 2007-2012)
Main eligibility criteria
• Patients ≥ 18 years with pathologically confirmed diagnosis of colorectal adenocarcinoma
• First-line chemotherapy for metastatic disease with oral or intravenous fluoropyrimidine alone, or in combination with irinotecan or oxaliplatin
• Chemotherapy must have been given in combination with standard dose of BEV for at least 16, but no longer than 24 weeks as part of the first-line treatment
• Last administration of BEV within 4 weeks before randomization
• Stable disease (SD), partial response (PR) or complete response (CR) after end of chemotherapy/BEV first-line treatment (tumor assessment within 21 days before randomization)
Endpoints
Primary endpoint:
• Time to progression (TTP)– Measured by CT-scans q 6 weeks from randomization until PD
Secondary endpoints:
• Progression free survival (PFS)• Time to second-line treatment • Overall survival (OS) • Adverse events related to BEV • Treatment costs
Statistical considerations• Non-inferiority study
– Assumption: TTP of ≤ 22 weeks for BEV continuation TTP of ≥16 weeks for no BEV
– Hypothesis: BEV vs. no BEV Hazard Ratio (HR) HR ≥ 16/22 = 0.727
• 219 events required for a significance level of 10%, a power of 85% to detect a HR=1, one interim analysis
• Analysis based on 262 evaluable patients (131 in each arm)
Patient characteristicsCharacteristic (% patients) BEV (n=131) No BEV (n=131)
