HERCEPTIN

AVASTIN
AVEX (Bevacizumab + Capecitabine; ≥70 y/o)

Open-label, randomised phase III trial

Capecitabine:
Avastin 7.5 mg/kg q3w +
1000 mg/m² orally twice a day
Xeloda (1000 mg/m2 b.i.d, days 1-14)
(n=140) on days 1–14
Previously untreated
mCRC, age ≥70 years R Bevacizumab:
(n=280) 7·5 mg/kg intravenously on day
1), given every 3 weeks until
disease progression
Xeloda (n=140)

Reference:
Cunningham D, Lang I, Marcuello E et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously
untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013; 14: 1077–1085
AVEX: Avastin + Xeloda significantly increase PFS in patients
aged ≥70 years

PFS OS*
100 Avastin + Xeloda (n=140) 1 Avastin + Xeloda
Xeloda (n=140)
HR 0.53
0 (n=140)
80 0
8
p<0.0001
Xeloda (n=140)
0
HR 0.79
60 6

OS (%)
PFS (%)

0 p=0.182
40 4
0
20 2
0
5.1
0
9.1
0 16 20
0 6 12 18 24 30 36 42
0 6 1.8 1 .72 3 3 4 4
Time (months) 2 8 Time4 0 6 2 6
*Study was not powered to detect differences in OS between treatment arms
(months)

Reference:
Cunningham D, Lang I, Marcuello E et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously
untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013; 14: 1077–1085
AVEX: Exploratory subgroup analyses of PFS were consistent
with the overall findings
Avastin + Xeloda Xeloda
alone
Category Subgroup N better HR (95% CI)
better
All All 280 0.53 (0.41-0.69)
Sex Female 112 0.47 (0.30-0.72)
Male 168 0.57 (0.41-0.80)
Age <75 years 101 0.52 (0.32-0.83)
≥75 years 179 0.52 (0.37-0.72)
Baseline ECOG performance status 0 130 0.61 (0.41-0.89)
>1 147 0.50 (0.34-0.72)
Prior adjuvant therapy No 206 0.51 (0.37-0.69)
Yes 71 0.59 (0.33-1.04)
Liver metastases only No 162 0.53 (0.38-0.75)
Yes 106 0.54 (0.35-0.83)
Surgical resection No 86 0.27 (0.16-0.48)
Yes 192 0.62 (0.45-0.85)
Location of primary disease Colon only 157 0.67 (0.47-0.94)
Rectum and colon 42 0.22 (0.08-0.56)
Rectum only 79 0.41 (0.24-0.69)

0.2 0.5 1.0 1.5 2.0

Hazard
ratio
Reference:
Cunningham D, Lang I, Marcuello E et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously
untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013; 14: 1077–1085
AVEX: More patients treated with Avastin + Xeloda had an overall response to
treatment than those in the Xeloda group

Outcome Avastin + Xeloda Xeloda

(n=140) (n=140)

ORR (CR + PR) 27 (19%) 14 (10%)

P=0.04

CR 3 (2%) 2 (1%)

PR 24 (17%) 12 (9%)

SD 77 (55%) 67 (48%)

PD 14 (10%) 30 (21%)

Disease control rate (CR + PR + SD) 104 (74%) 81 (58%)

P=0.01

Missing 22(16%) 29 (21%)

ITT population. CR = complete response; PD = disease progression; PR = partial response; SD = stable disease.

Reference:
Cunningham D, Lang I, Marcuello E et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously
untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013; 14: 1077–1085
AVEX: Proportions of patients affected by AEs and treatment-related AEs
of any grade were similar between groups

Avastin + Xeloda (n=134) Xeloda (n=136)

Any cause Related to treatment Any cause Related to treatment

Any adverse event 129 (96%) 112 (84%) 130 (96%) 110 (81%)

Any grade ≥ adverse 81 (60%) 53 (40%) 60 (44%) 30 (22%)

event

Any serious adverse 40 (30%) 19 (14%) 42 (31%) 11 (8%)

event

Grade 5 adverse event 9 (7%) 5 (4%) 14 (10%) 4 (3%)

(death)

Any adverse event

leading to dose 74 (55%) NA* 59 (43%) NA*
interruption or
modification

Any adverse event

leading to 34 (25%) NA* 20 (15%) NA*
discontinuation

* Not recorded as being related or unrelated to treatment

Additional
Info

Reference:
Cunningham D, Lang I, Marcuello E et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously
untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013; 14: 1077–1085
 AVEX (Bevacizumab + Capecitabine; ≥70 y/o)

● Adding Avastin to Xeloda provides benefits that are statistically significant and clinically
relevant.5

● No new safety signals, and the safety profile was consistent with that reported by other
studies of Avastin + Xeloda in mCRC5

● Results from AVEX suggest that the combination of Avastin and Xeloda is an effective and
well-tolerated regimen for elderly patients with mCRC5

References:
1. Venook AP, Niedzwiecki D, Lenz HJ et al. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer:A Randomized Clinical Trial. JAMA. 2017;317(23):2392-2401.
2. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. N Engl J Med 2004;350:2335-2342.
3. Simkens LHJ, Van Tinteren H, May A et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015 May 9;385(9980):1843-1852
4. Cremolini C, Loupakis F, Antoniotti C et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015
Oct;16(13):1306-1315.
5. Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1077-1085
6. Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013 Jan;14(1):29-37
7. Giantonio BJ, Catalano PJ, Meropol NJ et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007 Apr 20;25(12):1539-1544.