Abstract 1374P
Background
This phase III study evaluated whether combination therapy has superior efficacy to monotherapy in elderly patients with advanced gastric cancer (AGC).
Methods
Elderly (≥ 70 years) chemo-naïve patients were randomly assigned to receive either combination therapy (arm A: capecitabine/cisplatin, capecitabine/oxaliplatin, S-1/cisplatin, or 5-FU/oxaliplatin) or monotherapy (arm B; capecitabine, S-1, or 5-FU). Randomization was stratified by age (< 75; ≥ 75 years), ECOG performance status (0,1; 2), and fluoropyrimidine backbone (capecitabine; S-1; 5-FU). Starting doses were 80% of standard doses in the arm A, with discretionary escalation to full dose after 1 cycle. The primary objective was to confirm superior overall survival (OS) of combination therapy to monotherapy.
Results
After 111 of the 238 patients planned were enrolled, this study was terminated due to poor accrual. In the full-analysis population, with a median follow up of 9.5 months (range, 0.3-71.2), median OS for combination versus monotherapy was 11.5 versus 7.5 months (Hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.56-1.30, P=0.2308). Median progression-free survival (PFS) was 5.6 versus 3.7 months (HR = 0.53, 95% CI 0.34-0.83, P = 0.0046). In a subgroup analysis, patients with 70-74 years tended to have superior OS with combination versus monotherapy (15.9 versus 7.2 months [HR=0.53, 95% CI 0.28-1.03, P =0.056]). Treatment-related adverse events (all grades) occurred more frequently in the arm A versus arm B: neutropenia (43.4% versus 21.6%), thrombocytopenia (41.5% versus 19.6%), fatigue (47.2% versus 27.5%), diarrhea (22.6% versus 11.8%), and vomiting (15.1% versus 9.8%). Common grade 3/4 adverse events were anemia (11.3%) and nausea (5.7%) in the arm A, and anemia (7.8%) and hyponatremia (3.9%) in the arm B.
Conclusions
Combination therapy did not show superiority for OS, but had significant PFS benefit versus monotherapy in the first-line treatment of elderly patients with AGC. Combination therapy was well tolerated, though frequent adverse events occurred. Patients with 70-74 years would benefit more from combination therapy.
Clinical trial identification
NCT02114359.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National R & D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (132054).
Disclosure
All authors have declared no conflicts of interest.