The Evolving Standard of Care in Gastric Cancer

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Presentation transcript:

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

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. www.cancer.gov

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;20:1529-1534.

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;72:37-41. 2. Vanhoefer U et al. J Clin Oncol. 2000;18:2648-2657. 3. Van Cutsem E et al. J Clin Oncol. 2006;24:4991-4997 4. Dank M et al. J Clin Oncol. 2005;23[Suppl 16S]:4003. 5. Cunningham et al. N Engl J Med. 2008;358:36-46. 6. Kang Y et al. J Clin Oncol . 2006;22[Suppl 18S]:LBA4018.

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.

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.

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 228 218 218 198 196 170 170 141 142 112 122 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.

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.

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.

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.

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 10-11 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