Many patients with advanced gastroesophageal cancer are older and can be frail. A previous pick-the-winner study compared three treatment regimens: epirubin, oxaliplatin, and capecitabine; oxaliplatin and capecitabine; and capecitabine alone. The results indicated that oxaliplatin and capecitabine was the best option.
The phase II GO2 clinical trial was designed to identify the optimum dose of oxaliplatin and capecitabine and explore the use of an objective baseline geriatric assessment to individualize doses for maximum Overall Treatment Utility (OTU), a composite of clinical benefit, tolerability, quality of life (QOL), and patient value. The results were presented at the 2019 ASCO Annual Meeting.
Eligible patients with advanced gastroesophageal cancer were unsuitable for full-dose epirubin, oxaliplatin, and capecitabine therapy due to age or frailty but were fit for oxaliplatin and capecitabine. Patients had a glomerular filtration rate (GFR) ≥30 and bilirubin less than two times the upper limit of normal (ULN).
At baseline, researchers assessed global QOL, symptoms, functional scales, comorbidity, and frailty. A total of 514 patients were enrolled from 61 United Kingdom centers between 2014 and 2017. Patients were randomized 1:1:1 to receive:
- Level A: oxaliplatin 130 mg/m2 on day one and capecitabine 625 mg/m2 (n=170; median age, 76 years)
- Level B: 80% Level A doses (n=171; median age, 76 years)
- Level C: 60% Level A doses (n=173; median age, 77 years)
Patients with GFR 30 mL/min to 50 mL/min or bilirubin 1.5 to two times the ULN received 75% of the allocated dose of capecitabine.
At nine weeks, patients were scored for OTU. Noninferiority of progression-free survival (PFS) was confirmed for Level B versus Level A (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.89-1.32) and for Level C versus Level A (HR=1.10; 95% CI, 0.90-1.33). Level C patients had less toxicity and better OTU outcomes than Levels A or B.
Median PFS was 4.9 months for Level A, 4.1 months for Level B, and 4.3 months for Level C. Median OS was 7.5 months for Level A, 6.7 months for Level B, and 7.6 months for Level C.
When researchers analyzed outcomes based on baseline age, frailty, and performance status, Level C produced the best OTU even in patients who were younger, less frail, and had better performance status scores.
No patients benefitted more from the higher dose levels, and the researchers said the findings should guide future treatment.
Hall PS, Swinson D, Waters JS, et al. Optimizing chemotherapy for frail and elderly patients (pts) with advanced gastroesophageal cancer (aGOAC): The GO2 phase III trial. Abstract #5551. Presented at the 2019 ASCO Annual Meeting, Chicago, IL, June 2, 2019.