Type of publication:
Randomised controlled trial
Hall, Peter S; Swinson, Daniel; Cairns, David A; Waters, Justin S; Petty, Russell; Allmark, Christine; Ruddock, Sharon; Falk, Stephen; Wadsley, Jonathan; Roy, Rajarshi; Tillett, Tania; Nicoll, Jonathan; Cummins, Sebastian; Mano, Joseph; Grumett, Simon; Stokes, Zuzana; Konstantinos-Velios, Kamposioras; *Chatterjee, Anirban; Garcia, Angel; Waddell, Tom; Guptal, Kamalnayan; Maisey, Nick; Khan, Mohammed; Dent, Jo; Lord, Simon; Crossley, Ann; Katona, Eszter; Marshall, Helen; Grabsch, Heike I; Velikova, Galina; Ow, Pei Loo; Handforth, Catherine; Howard, Helen; Seymour, Matthew T; GO2 Trial Investigators
JAMA oncology; May 2021; 7(6):869-877
Importance Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. ObjectiveThe GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making.Design, Setting, and Participants This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty.InterventionsThere were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m2 on day 1, capecitabine 625 mg/m2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care.Main Outcomes and MeasuresFirst, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registrationisrctn.org Identifier: ISRCTN44687907.
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