1. 1Cancer Research UK, Glasgow, United Kingdom
Surgery with curative intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer (mCRC): First BEAT and NO16966
J. Cassidy,1 D. Cunningham,2 S. Berry,3 F. Rivera,4 S. Clarke,5 A. Kretzschmar,6 E. Diaz-Rubio,7 E. Van Cutsem,8 L. Saltz,9 on behalf of the First BEAT and NO16966 investigators
1Cancer Research UK, Glasgow, United Kingdom

2. First BEAT: study overview
First-line metastatic CRC (1,965)
Bevacizumab + standard chemotherapy PD
Bevacizumab: 5mg/kg q2w or 7.5mg/kg q3w
Chemotherapy at physician’s discretion
Primary endpoint: safety
surgery prospectively assessed
Enrolment: June 2004–February 2006
At follow-up 1 February 2008, data available for 1,914 patients
Median follow-up 21.1 months
Data for surgery were assessed prospectively

3. BEAT: Hepatic metastasectomy – all patients
Hepatic metastasectomy with R0 resection
n=145
7.6%
Bevacizumab + CT
(all; n=1,914)
n=114
6.0%
n=99
10.5%
Bevacizumab + CT incl. oxaliplatin (n=946)
n=76
8.0%
n=43
6.5%
Bevacizumab + CT incl. irinotecan (n=662)
n=34
5.1%
Patients (%)

4. BEAT: Surgery-related complications
Grade 3/4 adverse events or serious adverse events
n=225
Wound-healing complications
1.3%
Bleeding
0.4%

5. BEAT: Overall survival – hepatic metastasectomy with R0 resection
Patients with curative hepatic metastasectomy and R0 resection (n=114)
Patients without curative hepatic metastasectomy (n=1,791)
1.00
0.75
0.50
0.25
89%
Overall survival estimate
47%
p<0.001
Months

6. NO16966: study overview Recruitment June 2003–May 2004
Recruitment February 2004–February 2005
XELOX + placebo
(n=350)
FOLFOX4 + placebo (n=351)
XELOX + bevacizumab
FOLFOX4 + bevacizumab
(n=349)
XELOX (n=317)
FOLFOX4
(n=317)
Initial two-arm open-label study (n=1,000)
Protocol amended to 2x2 placebo- controlled design after bevacizumab phase III data became available (n=1,400)
Data for surgery with curative intent were assessed retrospectively

7. NO16966: Overall survival in patients with R0 resection
FOLFOX4/XELOX + placebo
n=665
38%
FOLFOX4/XELOX + bevacizumab
Patients without R0 resection
n=649
40%
Patients with R0 resection
FOLFOX4/XELOX + placebo
n=34
82%
FOLFOX4/XELOX + bevacizumab
91%
n=44
2-year overall survival (%)

8. Conclusions
Hepatic metastasectomy was performed in ~8% of patients receiving bevacizumab-based therapy
R0 outcome in ~80%
low rate of bleeding and wound-healing complications
2-year overall survival rates of ~90% in patients with R0 resection
Safety and feasibility of hepatic metastasectomy with curative intent does not appear to be compromised in patients receiving bevacizumab plus chemotherapy