1. Quality of life results from a Phase III trial of trastuzumab plus chemotherapy in first-line HER2-positive advanced gastric and GE junction cancer Taroh Satoh* *Kinki University School of Medicine, Osaka, Japan J León Chong, RI López Sanchez, D Ferry, Y-J Bang, E Van Cutsem, N Al-Sakaff, J Hill, S Donelson Trease, G Aprile

2. Disclosures Travel support from: Chugai Pharmaceutical Consultancy fees from: Chugai Pharmaceutical Merck-Serono Sanofi-Aventis Bristol-Myers Yakult Pharmaceutical Taiho Pharmaceutical Daiichi-Sankyo

3. Gastric cancer overview Gastric cancer is the fourth most commonly diagnosed cancer and the second most common cause of cancer- related deaths worldwide 1,2 Despite an overall decrease in gastric cancer there is a growing incidence of gastro-esophageal (GE) junction tumors in developed countries 3 Advanced/metastatic gastric cancer has a poor prognosis Median 5-year survival rate of around 20% 2 There is an unmet need for more efficacious and less toxic treatment options in advanced GC 1. Kamangar F, et al. J Clin Oncol 2006; 24:2137–2150. 2. Garcia M, et al. Global Cancer Facts and Figures 2007. Atlanta GA: American Cancer Society 2007. 3. Kusano C, et al. J Gastroenterol Hepatol 2008; 23:1662–1665.

4. ToGA trial design HER2-positive advanced GC (n=584) Capecitabine or 5-FU + cisplatin (XP/FP) (n=290) R 5-FU, 5-fluorouracil; GC, gastric cancer; R, randomised. Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509. Capecitabine or 5-FU + cisplatin (XP/FP) + trastuzumab (n=294) ●Primary objective: overall survival (OS) ●Secondary endpoints included: PFS, TTP, ORR, Clinical Benefit Rate, Duration of Response, safety, quality of life, pain intensity, analgesic consumption 3,807 patients screened; 810 HER2-positive ●Phase III, randomized, global study to evaluate the efficacy and safety of trastuzumab in patients with advanced, HER2-positive adenocarcinoma of the stomach or GE junction

5. OS in the full analysis set Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509. Median OSHR95% CIp-value Trastuzumab + XP/FP 16713.8 mo0.740.60, 0.910.0046 XP/FP18211.1 mo Time (months) 11.113.8 024681012141618202224262830323436 Events 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Probability 294 290 277 266 246 223 209 185 173 143 147 117 113 90 64 71 47 56 32 43 24 30 16 21 14 13 7 12 6 6565 4040 1010 0000 No. at risk

6. OS in IHC 2+/FISH+ or IHC 3+ patients (exploratory analysis) Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509. Median OSHR95% CI Trastuzumab + XP/FP 12016.0 mo0.650.51, 0.83 XP/FP13611.8 mo 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Time (months) Events 11.816.0 246810121416182022242628303234360 Probability 11 3 218 198 5353 12 4 20 11 228 218 196 170 170 141 142 112 122 96 100 75 84 53 65 39 51 28 39 20 28 13 No. at risk 0000 1010 4040

7. 0246810121416182022242628303234 294 290 258 238 201 182 141 99 95 62 60 33 41 17 28 7 21 5 13 3 9393 8282 6262 6161 6161 4040 2020 0000 5.56.7 No. at risk 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Time (months) Trastuzumab + XP/FP XP/FP Events 226 235 HR 0.71 95% CI 0.59, 0.85 p value 0.0002 Median PFS 6.7 5.5 Probability PFS in the full analysis set Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509.

8. Methods: QoL assessments 1. Vickery CW, et al. Eur J Cancer 2001; 37:966–971. 2. Blazeby JM, et al. Eur J Cancer 2004; 40:2260–2268. Evaluated in the full analysis set (FAS) population at Day 1 and every 3 weeks (prior to drug administration), until disease progression EORTC QLQ-C30 questionnaire (v 3.0): 1,2 Global health status, functional scales, symptom scales EORTC QLQ-ST022 questionnaire (disease-specific module for gastric cancer): 1,2 Symptom scales included items for disease, treatment-related symptoms, side effects, dysphagia, nutritional aspects, emotional problems The scoring range for both QLQ-C30 and QLQ-ST022 was from 0–100 Pain intensity assessed by Visual Analog Scale (VAS) Analgesic consumption for gastric pain

9. Compliance At baseline, >95% of patients in both treatment arms completed the EORTC QLQ-C30 and EORTC QLQ-ST022 questionnaires Compliance remained high for patients continuing in the study Compliance to QLQ-C30, n/N (%) Visit Trastuzumab + Chemotherapy (n=294) Chemotherapy alone (n=290) Baseline287/294 (97.6%)276/290 (95.2%) Week 16165/168 (98.2)121/126 (96.0) Week 25124/129 (96.1)64/69 (92.8) Week 3487/89 (97.8)37/39 (94.9)

10. *Higher global health score indicates better QoL; B/L, baseline EORTC QLQ-C30: global health status scores improved over time B/L 50 4710131619222528313437404346495255586164 55 60 75 80 85 90 Score (mean ± SEM)* Time (weeks) 70 65 Duration of chemotherapy Trastuzumab + Chemotherapy (n=287) Chemotherapy alone (n=274) N 235180176152121114786447453629231213975543274Chemo 287249220202182165143 124111958764554342362924 21 1720T + chemo

11. EORTC QLQ-C30: physical functioning scores improved over time Trastuzumab + Chemotherapy (n=287) Chemotherapy alone (n=276) B/L 70 4710131619222528313437404346495255586164 75 80 85 80 95 100 Score (mean ± SEM)* Time (weeks) *Higher functioning score indicates better QoL; B/L, baseline Duration of chemotherapy N 2351811741511211147964474537292412141086643276Chemo 287250220201183165143 124110958764554342363024 21 1720T + chemo

12. *Lower symptom score indicates better QoL; B/L, baseline EORTC QLQ-C30: symptom scores for nausea/vomiting improved over time 5 10 15 20 25 Score (mean ± SEM)* 0 B/L4710131619222528313437404346495255586164 Time (weeks) Duration of chemotherapy Trastuzumab + Chemotherapy (n=287) Chemotherapy alone (n=276) N 2351811761521211147964474537292412141086643276Chemo 287250220201183165143 124110958764554342363024 21 1720T + chemo

13. EORTC QLQ-ST022: mean dysphagia score improved over time 5 10 15 20 0 Score (mean ± SEM)* B/L4710131619222528313437404346495255586164 Time (weeks) Trastuzumab + Chemotherapy (n=287) Chemotherapy alone (n=276) Duration of chemotherapy *Lower symptom score indicates better QoL; B/L, baseline N 287250220203183165143 124111958764554342363024 21 1720T + chemo 2341811761521201147964474537292412141086643276Chemo

14. No difference in VAS pain intensity scores over time Trastuzumab + Chemotherapy (n=284) Chemotherapy alone (n=275) 5 10 20 25 0 Score (mean ± SEM)* B/L4710131619222528313437404346495255586164 Time (weeks) *Lower pain intensity score indicates better QoL; B/L, baseline 15 Duration of chemotherapy N 2341811741521211147964474537292412141086643275Chemo 284249219202181165142141124111958664544341363024 20 1720T + chemo

15. Analgesic medication for gastric pain during the study Patients, n (%) Trastuzumab + Chemotherapy n=294 Chemotherapy alone n=290 Any analgesic medication86 (29)84 (29) Discontinued at least one medication 5 (2)17 (6) Decreased dose of at least one medication 1 (<1) No change in any medication21 (7)16 (6) Increased dose or added at least one medication 59 (20)50 (17)

16. Conclusions Trastuzumab + chemotherapy improves OS and PFS versus chemotherapy alone, without compromising QoL Disease-specific and symptom-specific scores improved over time in both treatment arms Pain intensity scores and use of analgesic medicine were similar between treatment arms Associated with prolonged PFS more patients in the trastuzumab + chemotherapy arm could benefit from the improved QoL compared to chemotherapy alone

17. Acknowledgements The authors would like to thank: The patients The investigators, co-investigators and study teams at the 142 centres in 24 countries (in Asia, Australia, Europe, Latin-America, and South Africa) The study team at Roche Targos Molecular Pathology GmbH