Quality of Life Associated with Ramucirumab Treatment in Patients with Advanced Gastric Cancer in Japan: Exploratory Analysis from the Phase III RAINBOW Trial

Abstract

Background and objective: Gastric cancer has been associated with notable geographic heterogeneity in previous multi-regional studies. In particular, patients from Japan have better outcomes compared with patients from other regions. Here, we assess patient-focused outcomes for the subgroup of Japanese patients in the global RAINBOW study.

Methods: Quality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) at baseline and 6-week intervals. Investigators assessed performance status before each 4-week cycle. Time-to-deterioration in each QLQ-C30 scale was defined as randomization to first worsening of ≥ 10 points (on a 100-point scale). Time-to-deterioration in performance status was defined as first worsening to ≥ 2. Hazard ratios were estimated using Cox proportional hazards models.

Results: The Japan subgroup contained 140 patients (ramucirumab plus paclitaxel, n = 68; placebo plus paclitaxel, n = 72); baseline QoL data were available for all patients. At baseline, QLQ-C30 scores were similar between study arms. Of the 15 QLQ-C30 scales, nine had a hazard ratio < 1, indicating similar or numerically longer time-to-deterioration in QoL for ramucirumab plus paclitaxel; all 95% confidence intervals included 1. Best mean change from baseline numerically favored ramucirumab plus paclitaxel in most QoL scales. The hazard ratios for time-to-deterioration of performance status to ≥ 2 were 0.64 in the Japan subgroup and 0.88 in the non-Asian subgroup. The Japan subgroup had better QoL at baseline compared with the non-Asian subgroup.

Conclusions: Treatment with ramucirumab plus paclitaxel maintained QoL and performance status over time compared with placebo plus paclitaxel in the Japan subgroup of the RAINBOW trial. These data suggest that the heterogeneity in gastric cancer between geographic regions includes multiple measures of QoL.

Trial registration number: NCT01170663 (first submitted 21 July, 2010).

Conflict of interest statement

Kensei Yamaguchi received grants and personal fees from Eli Lilly and Company. Shuichi Hironaka received personal fees from Bristol-Myers Squibb, Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Yakult Honsha Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly and Company, Chugai Pharmaceutical Co. Ltd., Nihonkayaku, and Tsumura and Co. Yoshito Komatsu reports fees from Ono Pharmaceutical Co. Ltd., Merck Sharp & Dohme, Eli Lilly and Company, AstraZeneca, Daiichi Sankyo Co. Ltd., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Linical Co. Ltd., Tennessee Coalition for Open Government, Nassau Community College, Kyowa Hakko Kirin Co. Ltd., Takeda Pharmaceutical Co. Ltd., Sanofi, Yakult Honsha Co. Ltd., Bristol-Myers Squibb, Boehringer Ingelheim, Bayer, Pfizer, and Novartis. Takao Tamura reports grants and personal fees from Chugai Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Ono Pharmaceutical Co. Ltd., Merck Serono Co. Ltd, Bristol-Myers Squibb, and Takeda Pharmaceutical Co. Ltd. Yongzhe Piao, Gosuke Homma, Min-Hua Jen, and Astra M. Liepa are employees of Eli Lilly and Company and received salaries. Min-Hua Jen and Astra M. Liepa are also shareholders of Eli Lilly and Company. Yasuhiro Shimada, Naotoshi Sugimoto, Tomohiro Nishina, Yasushi Omuro, and Kei Muro have no conflicts of interest that are directly relevant to the content of this article.

Figures

Fig. 1

Quality-of-Life Questionnaire-Core 30 (QLQ-C30) scores by treatment arm at baseline a Japan and b Non-Asian. Non-Asian comprised patients in regions other than East Asia (i.e., patients enrolled from Argentina, Australia, Brazil, Chile, Europe, Israel, Mexico, and USA). *The baseline data were not available for all patients and ‘N’ varied (ramucirumab and paclitaxel arm: 214–215; placebo plus paclitaxel arm: 215–217). Error bars represent standard deviation; scores range from 0 to 100 (y-axis runs to 120 because of error bars); for functional scales and global quality of life (QoL), higher score = better QoL; for symptom and financial difficulties scales, lower score = better QoL

Fig. 2

European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 mean of best change from baseline within arm and treatment arm difference. Error bars represent standard error. QoL quality of life

Fig. 3

Summary of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) response analysis over time for select scales a global quality of life; b physical functioning; c role functioning; d fatigue; e pain; and f appetite loss. All patients included to derive percentages (ramucirumab plus paclitaxel, n = 68; placebo plus paclitaxel, n = 72); ‘No data’ was primarily due to discontinuation of therapy related to tumor progression. The QLQ-C30 response analysis characterized each post-baseline assessment as improved or deteriorated if the change was ≥ 10 points, and stable if the change was <10 points for each of the scales

Fig. 4

Time to deterioration in Quality-of-Life Questionnaire-Core 30 (QLQ-C30) scales. CI confidence interval, HR hazard ratio, QoL quality of life

Fig. 5

Kaplan–Meier plots of time to deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 a Japan and b Non-Asian. CI confidence interval, HR hazard ratio