PD-0026 Quality of Life in Patients with Advanced Gastric Cancer Enrolled in the International, Phase 3 Granite-1 Study

Abstract

ABSTRACT Introduction Advanced gastric cancer is an aggressive, difficult-to-treat disease associated with poor outcomes. Treatment options for patients who progress after first- or second-line chemotherapy are limited, particularly as many patients have poor performance status (PS) and are not eligible for additional chemotherapy. Advanced gastric cancer treatment options that improve outcomes without significantly decreasing quality of life (QoL) are needed. Methods In the randomized, double-blind, phase 3 GRANITE-1 study, patients aged ≥18 years with confirmed advanced gastric cancer, disease progression after 1 or 2 lines of previous systemic chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) PS ≤2 were randomized 2:1 to oral everolimus 10 mg/day plus best supportive care (BSC) or placebo plus BSC. Randomization was stratified by region (Asia [China, Japan, Korea, Taiwan, Thailand, and Hong Kong] vs rest of the world) and by the number of previous lines of systemic chemotherapy (1 vs 2). Study drug was continued until disease progression or unacceptable toxicity. ECOG PS was assessed at baseline, every 2 weeks for the first 4 weeks, and every 4 weeks thereafter until the end of treatment. The European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 QoL questionnaire and gastric-specific STO22 module were completed at the start of treatment and every 4 weeks thereafter until disease progression. The primary endpoint was overall survival (OS). Secondary endpoints included the time to definitive deterioration of ECOG PS, defined as a decrease of ≥1 category and no subsequent improvement, and the time to a definitive 5% deterioration in the global health status/QoL and physical, social, and emotional functioning scales of the QLQ-C30 questionnaire. Results A total of 656 patients (median age, 62.0 years; 73.6% male; 91.9% with ECOG PS ≤1) were enrolled in the study and received everolimus (n = 439) or placebo (n = 217). Median OS was 5.39 months with everolimus and 4.34 with placebo (HR for OS, 0.90; 95% CI, 0.75-1.08; P = 0.1244). The median time to definitive deterioration in ECOG PS by ≥1 category did not differ between treatment groups (2.30 months with everolimus vs 2.23 months with placebo; HR, 0.96; 95% CI, 0.76-1.20; P = 0.6925). A trend for slightly longer time to definitive 5% deterioration in global QoL was observed with everolimus vs placebo (median, 1.51 months vs 1.45 months; HR for definitive 5% deterioration from baseline, 0.84; 95% CI, 0.69-1.03; P = 0.0936). Trends for slightly longer time to definitive 5% deterioration in the social (HR, 0.87; 95% CI, 0.70-1.09; P = 0.2108) and emotional (HR, 0.83; 95% CI, 0.67-1.02; P = 0.0735) functioning scales were also observed; no difference between treatment groups was detected for physical functioning (HR, 0.95; 95% CI, 0.78-1.15; P = 0.5711). Over time, everolimus recipients had higher mean scores for the emotional functioning subscale of the QLQ-C30 and lower mean scores (i.e., lower level of symptoms) for the pain and reflux subscales of the STO22 module. Conclusion Everolimus did not cause significant deterioration in ECOG PS or QoL in patients with previously treated advanced gastric cancer.