3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT

Health Technology Assessment

卷:23

Charles Wilson¹  Andrew Haydon²  Sherif Raouf³  David Propper⁴  Ashita Waterston⁵  Andrew Webb⁶  Stephen Falk⁷  Jim Cassidy⁸  Karen Allan⁸  Andrea Harkin⁸  John McQueen⁸  Amandeep S Dhadda⁹  Niels Henrik Hollander¹⁰  Rene K Olesen¹¹  Andrew Weaver¹²  John Bridgewater¹³  Rachel S Kerr¹⁴  David Farrugia¹⁵  Harpreet Wasan¹⁶  Andrew H Briggs¹⁷  Kathleen A Boyd¹⁷  Jose Robles-Zurita¹⁷  Mark Harrison¹⁸  Ashraf Azzabi¹⁹  Simon Gollins²⁰  Sarah Pearson²¹  Tamas Hickish²²  Richard Ellis²³  David Cunningham²⁴  Louise Medley²⁵  Charlotte Rees²⁶  Timothy Iveson²⁶  Sharadah Essapen²⁷  James Paul²⁸  Mark P Saunders²⁸  Bengt Glimelius²⁹  Josep Tabernero³⁰ 

[1] Addenbrooke’s Hospital, Cambridge, UK;

[2] Australasian Gastro-Intestinal Trials Group, Camperdown, NSW, Australia;

[3] Barking Havering and Redbridge University Hospital NHS Trust, Barking, UK;

[4] Barts Cancer Institute, Queen Mary University of London, London, UK;

[5] Beatson West of Scotland Cancer Centre, Glasgow, UK;

[6] Brighton and Sussex University Hospital Trust, Brighton, UK;

[7] Bristol Cancer Institute, Bristol, UK;

[8] Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK;

[9] Castle Hill Hospital, Hull, UK;

[10] Department of Oncology and Palliative Care, Zealand University Hospital, Naestved, Denmark;

[11] Department of Oncology, Aarhus University Hospital, Aarhus, Denmark;

[12] Department of Oncology, Oxford University Hospitals Foundation Trust, Oxford, UK;

[13] Department of Oncology, University College London, London, UK;

[14] Department of Oncology, University of Oxford, Oxford, UK;

[15] Gloucestershire Oncology Centre, Cheltenham General Hospital, UK;

[16] Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK;

[17] Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK;

[18] Mount Vernon Cancer Centre, Northwood, UK;

[19] Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK;

[20] North Wales Cancer Treatment Centre, Rhyl, UK;

[21] Oncology Clinical Trials Office, Department of Oncology, University of Oxford, Oxford, UK;

[22] Poole Hospital NHS Foundation Trust, Poole, UK;

[23] Royal Cornwall Hospitals NHS Trust, Cornwall, UK;

[24] Royal Marsden NHS Foundation Trust, London, UK;

[25] Royal United Hospital, Bath, UK;

[26] Southampton University Hospital NHS Foundation Trust, Southampton, UK;

[27] St Luke’s Cancer Centre, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK;

[28] The Christie Hospital NHS Foundation Trust, Manchester, UK;

[29] University of Uppsala, Uppsala, Sweden;

[30] Vall d’Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain;

关键词: oxaliplatin;    capecitabine;    disease-free survival;    chemotherapy;    adjuvant;    quality-adjusted life-years;    colorectal neoplasms;    fluorouracil;    randomised controlled trial;   

DOI  :  10.3310/hta23640

来源: DOAJ

【 摘 要 】

Background: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. Objectives: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. Design: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. Setting: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. Participants: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. Interventions: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. Main outcome measures: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. Results: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand–foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years (p < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4–6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient. Conclusions: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019–20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease. Trial registration: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre – Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894).

【 授权许可】

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