1. The Evolving Standard of Care in Gastric Cancer
Josep Tabernero, MD
Head of the Gastrointestinal Tumors and Phase I Program Medical Oncology Department Vall d'Hebron University Hospital Barcelona, Spain

2. Gastric Cancer: A Prevalent Disease
Worldwide: 934,000 new cases and 700,000 deaths /year
5-year survival rate  20%
Gastric cancer
incidence
 20 / 100,000
 10 to  20 / 100,000
< 10 / 100,000
Parkin DM et al. CA Cancer J Clin .2005;55:74–108. Yang L. World J Gastroenterol. 2006;12;17–20.

3. Superior Overall Survival With Capecitabine: ML17032/REAL-2 Meta-Analysis
1.0
ITT population
0.8
Capecitabine (n = 654)
5-FU (n = 664)
0.6
Estimated probability
HR = 0.87 (95% CI: 0.77–0.98)
P = .027
0.4
0.2
9.4
10.6
0.0 1 2 3 4 5 6
Years
5-FU = 5-fluorouracil; ITT = intent-to-treat
Okines AF et al. Ann Oncol. 2009;20:

4. Progress in Advanced Gastric Cancer: Overall Survival With Capecitabine-Based Regimens
BSC1
FAMTX2
CF3
IF4
ECF5
EOF5
DCF3
XP6
ECX5
EOX5
Months
1. Murad AM et al. Cancer. 1993;72: Vanhoefer U et al. J Clin Oncol. 2000;18: Van Cutsem E et al. J Clin Oncol. 2006;24: Dank M et al. J Clin Oncol. 2005;23[Suppl 16S]: Cunningham et al. N Engl J Med. 2008;358: Kang Y et al. J Clin Oncol ;22[Suppl 18S]:LBA4018.

5. HER2-Positivity Rate in Advanced Gastric Cancer
ToGA population
Exploratory analysis
EMA licensed population
(IHC 2+/FISH+
or IHC 3+)
Eligible
for ToGA
(IHC 3+ and/or FISH+)
16%
22%
IHC 0/FISH+ or
IHC 1+/FISH+ 6%
78%
78%
Not eligible
for ToGA
Not eligible
for ToGA
AGC = advanced gastric cancer; FISH = fluorescence in situ hybridization; HER2 = human epidermal growth factor receptor 2; IHC = immunohistochemistry
Chung H et al. Eur J Cancer Suppl. 2009;7:364.

6. ToGA: Trastuzumab + XP/FP Improves OS vs XP/FP Alone
Events
Median OS HR
95% CI
P value
Trastuzumab + XP/FP
167
13.8 mo
0.74
0.60, 0.91
.0046
XP/FP
182
11.1 mo
1.0
0.9
0.8
0.7
0.6
Probability
0.5
0.4
0.3
0.2
11.1
13.8
0.1
0.0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Time (mo)
No. at risk
294
290
277
266
246
223
209
185
173
143
147
117
113 90 90 64 71 47 56 32 43 24 30 16 21 14 13 7 12 6 6 5 4 1
CI = confidence interval; HR = hazard ratio; OS = overall survival; XP/FP = capecitabine/5-FU + cisplatin
Van Cutsem E et al. J Clin Oncol. 2009;27[Suppl 15S]:Abstract 4509.

7. ToGA: OS in IHC 2+/FISH+ and IHC 3+ Subgroup (Exploratory Analysis)
Events
Median OS HR
95% CI
Trastuzumab + XP/FP
120
16.0 mo
0.65
0.51, 0.83
XP/FP
136
11.8 mo
1.0
0.9
0.8
0.7
0.6
Probability
0.5
0.4
0.3
0.2
0.1
11.8
16.0
0.0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Time (mo)
No. at risk
170
141
142
112
122 96
100 75 84 53 65 39 51 28 39 20 28 13 20 11 12 4 11 3 5 3 4 1
Van Cutsem E et al. J Clin Oncol. 2009;27[Suppl 15S]:Abstract 4509.

8. AVAGAST: Overall Survival
XP + Placebo
XP + Bevacizumab
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
HR = 0.87
95% CI 0.73–1.03
P = .1002
12.1
Survival rate
10.1 3 6 9 12 15 18 21 24
Study month
Number at risk
XP + Placebo
XP + Bev
387
343
355
271
291
204
232
146
178 98
104 54 50 15 19
Kang Y et al. J Clin Oncol. 2010;28[18Suppl]:Abstract LBA4007.

9. AVAGAST: PFS and ORR Survival rate 6.7 5.3 Study month
XP + Bevacizumab (n = 387)
XP + Placebo (n = 387)
ORR
143 (46%)
111 (37%)
P = .0315
1.0
0.8
0.6
0.4
0.2
XP + Placebo
XP + Bevacizumab
6.7
Survival rate
5.3
HR = 0.80
95% CI 0.68–0.93
P= .0037 3 6 9 12 15 18 21 24
Study month
PFS = progression-free survival; ORR = overall response rate
Kang Y et al. J Clin Oncol. 2010;28[18Suppl]:Abstract LBA4007.

10. AVAGAST: Regional Differences in Efficacy
XP + Placebo
Median, mo
XP + Bev
Delta, mo
Hazard Ratio
95% CI OS
Asia
12.1
13.9
1.8
0.97
0.75–1.25
Europe
8.6
11.1
2.5
0.85
0.63–1.14
Pan-America
6.8
11.5
4.7
0.63
0.43–0.94
PFS
5.6
6.7
1.1
0.92
0.74–1.14
4.4
6.9
0.71
0.54–0.93
5.9
1.5
0.65
0.46–0.93
Kang Y et al. J Clin Oncol. 2010;28[18Suppl]:Abstract LBA4007.

11. Conclusions
Advanced gastric cancer continues to be an important malignant disease
With capecitabine-based chemotherapy, patients with advanced gastric cancer have attained a mean OS of months
Patients with HER-2 IHC 2+/FISH+ or IHC 3+ disease clearly benefit from addition of trastuzumab to standard chemotherapy
Some patients with advanced gastric cancer benefit from addition of antiangiogenic therapy to standard chemotherapy