Best supportive care (BSC) with or without low-dose chemotherapy (chemo) in frail elderly patients with advanced gastroesophageal cancer (aGOAC): The uncertain randomization of the GO2 phase III trial


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Daniel Swinson1,Peter Hall2,Mohan Hingorani3,Zuzani Stokes4,Jo Dent5,Kamalnayan Guptal6,Anirban Chatterjee7,Konstantinos Kamposioras8,Simon Aird Grumett9,Mohammad Khan10,Helen Marshall11,Ruddock Sharon11,Cairns David11,Christine Allmark12,Eszter Katona11,Helen C Howard11,Galina Velikova13,Simon Lord14,Matthew T Seymour15
1St James's University Hospital, Leeds, UK,2University of Edinburgh, Edinburgh.,3St James's University Hospital, Leeds.,4Lincolnshire Hospitals, Lincoln,5Calderdale and Huddersfield Royal Infirmary,6Worcester, United Kingdom,7Shrewsbury & Telford Hospitals, Shrewsbury,8Christie Hospital, Manchester,9Royal Wolverhampton Hospitals, Wolverhampton,10Scarborough Hospital, Scarborough,11CTRU, University of Leeds, Leeds,12NCRI Consumer Forum, London,13University of Leeds, Leeds,14University of Oxford, Oxford,15National Institute for Health Research Clinical Research Network, Leeds, United Kingdom

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. 

BSC aloneBSC + chemoPts (deaths)22(20)23(17).Median age78.579%PS ≥26857%frail; %very frail96; 6891; 70Mean baseline EQ5D QL (scale 0-1)0.640.61Median OS mo unadjusted3.06.1OS adjusted Cox modelHR= 0.69 [95%CI: 0.32-1.48], p=0.34Mean QL@9wks0.370.45

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.