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

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

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– Garcia M, et al. Global Cancer Facts and Figures Atlanta GA: American Cancer Society Kusano C, et al. J Gastroenterol Hepatol 2008; 23:1662–1665.

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

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 mo , XP/FP mo Time (months) Events Probability No. at risk

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 mo , 0.83 XP/FP mo Time (months) Events Probability No. at risk

No. at risk Time (months) Trastuzumab + XP/FP XP/FP Events HR % CI 0.59, 0.85 p value Median PFS Probability PFS in the full analysis set Van Cutsem E, et al. J Clin Oncol 2009; 27(18s):Abstract LBA4509.

Methods: QoL assessments 1. Vickery CW, et al. Eur J Cancer 2001; 37:966– 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

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)

*Higher global health score indicates better QoL; B/L, baseline EORTC QLQ-C30: global health status scores improved over time B/L Score (mean ± SEM)* Time (weeks) Duration of chemotherapy Trastuzumab + Chemotherapy (n=287) Chemotherapy alone (n=274) N Chemo T + chemo

EORTC QLQ-C30: physical functioning scores improved over time Trastuzumab + Chemotherapy (n=287) Chemotherapy alone (n=276) B/L Score (mean ± SEM)* Time (weeks) *Higher functioning score indicates better QoL; B/L, baseline Duration of chemotherapy N Chemo T + chemo

*Lower symptom score indicates better QoL; B/L, baseline EORTC QLQ-C30: symptom scores for nausea/vomiting improved over time Score (mean ± SEM)* 0 B/L Time (weeks) Duration of chemotherapy Trastuzumab + Chemotherapy (n=287) Chemotherapy alone (n=276) N Chemo T + chemo

EORTC QLQ-ST022: mean dysphagia score improved over time Score (mean ± SEM)* B/L Time (weeks) Trastuzumab + Chemotherapy (n=287) Chemotherapy alone (n=276) Duration of chemotherapy *Lower symptom score indicates better QoL; B/L, baseline N T + chemo Chemo

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

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)

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

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