Abstract

Background

Trials comparing BSC +/- chemo for aGOAC show overall survival (OS) benefit in predominantly fit patients (pts). We have revisited this question using low-dose chemo in a frail population, with comprehensive baseline health and frailty assessment.

Method

Elderly and/or frail aGOAC pts were randomised between 3 chemo doses. In this substudy, pts with an “uncertain” indication for chemo were instead randomised to BSC ± the lowest dose chemo. Both pt and clinician considered the indication for chemo uncertain, eGFR ≥30 and bili < 2xULN were required. Baseline assessment included globalQL, symptom & functional scales, frailty and comorbidity. Randomisation was 1:1 to BSC alone, or with oxaliplatin 78 mg/m2 d1, capecitabine 375 mg/m2 bd d1-21 (modified if eGFR 30-50 ml/min or bili 1.5-2.0 xULN), q21d. QL was reassessed after 9 and 18 wks. The primary endpoint was OS, adjusted for baseline factors. The sample size for this exploratory sub-study was not pre-set.

Results

558 pts entered GO2 at 61 centres 2014-17, 45 pts (8%) at 21 centres entered this uncertain randomisation providing 80% power at p = 0.05 (2-tailed) to detect an OS HR of 0.3. OS was shorter in pts with worse baseline PS (p<0.01) or distant mets (p<0.05). OS was not significantly improved with chemo although survival rates were higher after 3 months. QL and fatigue deteriorated less with BSC+chemo than with BSC alone. 

Conclusion

We observed a small non-significant survival benefit with chemo. Clinicians should consider BSC alone a valid treatment option for aGOAC pts with a limited life expectancy.