Gastrointestinal cancer

Optimizing chemotherapy for frail and/or elderly patient with advanced gastroesophageal cancer (AGOAC): the GO2 phase III trial (2019)

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Type of publication:
Conference abstract

Author(s):
Swinson D.E.; Hall P.; Seymour M.; Lord S.; Marshall H.; Ruddock S.; Cairns D.; Waters J.; Wadsley J.; Falk S.; Roy R.; Joseph M.; Nicoll J.; Vellios Kamposioras K.; Tillett T.; Cummins S.; Grumett S.; Stokes Z.; Waddell T.; *Chatterjee A.; Garcia A.; Allmark C.; Khan M.; Petty R.

Citation:
Journal of Geriatric Oncology; Nov 2019; vol. 10 (no. 6), Supplement 1, S8

Abstract:
Introduction: aGOAC patients are frequently elderly and/or frail.
Objective(s): (i) find the optimum dose of oxaliplatin capecitabine (OCap) for this population; (ii) explore the use of an objective geriatric assessment to individualize dose for maximum overall treatment utility (OTU), a composite of clinical benefit, tolerability, quality of life (QL) and patient value.
Method(s): Patients with aGOAC were eligible if there was uncertainty of the appropriate dose of chemotherapy. Baseline assessment included global QL; symptoms; functional scales; comorbidity; frailty. Randomization was 1:1:1 to dose Level A (Ox 130 mg/m2 d1, Cap 625 mg/m2 bd d1-21, q21d), B (80% Level A) or C (60% Level A). At 9 weeks, patients were scored for OTU. Non-inferiority (vs A) was assessed using PFS, censored at 12 months, with upper boundary HR 1.34 (based on patients' and clinicians' discussions), needing 284 PFS events per two-way comparison. In a separate sub-study, when there was uncertainty regarding the use of chemotherapy, patients were randomized between level C and supportive care alone (SCA).
Results and Conclusion(s): 512 patients were randomized, 2014-2017, at 61 UK centers. Age, performance status and frailty were similar in all arms. Non-inferiority of PFS is confirmed for Level B vs A (HR 1.09, CI 0.89-1.32) and for Level C vs A (HR 1.10, CI 0.90-1.33). Level C patients had the least toxicity and best OTU outcomes. When analyzed by baseline age, frailty and PS no group was identified who benefit more from higher treatment doses. A further 46 patients were randomized between chemotherapy and SCA. A non-significant trend to improved survival was observed (HR=0.69, CI 0.32-1.48) and QL deteriorated less with chemotherapy. This is the largest RCT specifically investigating frail and/or elderly aGOAC patients, and should guide future treatment. The lowest dose tested was non-inferior in terms of PFS, produced less toxicity and better overall treatment utility.

Best supportive care (BSC) with or without lowdose chemotherapy (chemo) in frail elderly patients with advanced gastroesophageal cancer (aGOAC): The uncertain randomization of the GO2 phase III trial (2019)

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Type of publication:
Conference abstract

Author(s):
Swinson D.; Hingorani M.; Stokes Z.; Dent J.; Guptal K.; *Chatterjee A.; Kamposioras K.; Grumett S.A.; Khan M.; Marshall H.; Ruddock S.; Allmark C.; Katona E.; Howard H.C.; Velikova G.; Lord S.; Hall P.S.; Seymour M.T.

Citation:
Journal of Clinical Oncology; May 2019; vol. 37

Abstract:
Background: Before 2000, trials comparing BSC +/chemo for aGOAC showed overall survival (OS) benefit, but in predominantly fit patients (pts). We have revisited this question in a modern context, using lowdose chemo in a frail population, with comprehensive baseline health and frailty assessment.
Method(s): In the GO2 trial, elderly and/or frail aGOAC pts with a ?certain? indication for chemo were randomised between 3 chemo doses. In this GO2 sub-study, pts with an ?uncertain? indication for chemo were instead randomised to BSC +/- the lowest dose chemo. Pts were eligible if clinician and pt agreed the indication for chemo was uncertain. There was no PS threshold, but eGFR >=30 and bili < 2xULN were required. Baseline assessment included global QL, 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 d121 (modified if eGFR 3050 ml/min or bili 1.52.0 xULN), q21d. QL was reassessed after 9 and 18 wks. The primary endpoint analysis was OS, adjusted for baseline factors. The sample size for this exploratory sub-study was not preset, but around 60 pts were anticipated.
Result(s): 558 pts entered GO2 at 61 centres 201417, of whom only 45 pts (8%) at 21 centres entered this uncertain randomisation. This would provide 80% power at p = 0.05 (2tailed) 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; however we cannot exclude HR >0.32. QL deteriorated less with BSC+chemo than with BSC alone.
Conclusion(s): In this frail, poor PS population, we observed a small survival benefit with chemo but this did not reach statistical significance. Clinicians should carefully consider BSC alone as a valid treatment option for aGOAC pts with poor PS and/or frailty.

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