Oxaliplatin/capecitabine or carboplatin/paclitaxel-based preoperative chemoradiation for resectable oesophageal adenocarcinoma (NeoSCOPE): long-term results of a randomised controlled trial
Oxaliplatin/capecitabine or carboplatin/paclitaxel-based preoperative chemoradiation for resectable oesophageal adenocarcinoma (NeoSCOPE): long-term results of a randomised controlled trial
Aim: this is the first randomised study to evaluate toxicity and survival outcomes of two neoadjuvant chemoradiotherapy (CRT) regimens for patients with localised oesophageal adenocarcinoma (OAC) or gastro-oesophageal junction (GOJ) adenocarcinoma. The initial results showed comparable toxicity between regimens and pathological complete response (pCR) rate favouring CarPacRT. Herein, we report survival, progression patterns, and long-term toxicity after a median follow-up of 40.7 months.
Methods: NeoSCOPE was an open-label, UK multicentre, randomised, phase II trial. Eighty-five patients with resectable OAC or GOJ adenocarcinoma, ≥cT3 and/or ≥cN1 (TNM v7), suitable for neoadjuvant CRT, were recruited between October 2013 and February 2015. Patients were randomised to OxCapRT (oxaliplatin 85 mg/m2 on Days 1, 15, and 29; capecitabine 625 mg/m2 orally twice daily on days of radiotherapy [RT]) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 on Days 1, 8, 15, 22, and 29). RT dose was 45 Gy/25 fractions/5 weeks. Both arms received induction chemotherapy (two cycles oxaliplatin 130 mg/m2 on Day 1, capecitabine 625 mg/m2 orally twice daily on Days 1-21) before CRT. Surgery was performed 6-8 weeks after CRT. The primary end-point was pCR. Secondary end-points were toxicity, progression-free survival (PFS), overall survival (OS), and patterns of progression.
Results: eighty-five patients were recruited from 17 UK centres. The median OS was 41.7 months (95% confidence interval [CI] 19.6 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable hazard ratio [HR] = 0.48, 95% CIs: 0.24-0.95, P = 0.035). The median PFS was 32.6 months (95% CIs: 17.1 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable HR = 0.54, 95% CIs: 0.29-1.01, P = 0.053). In both arms, the distant progression was twice as common as locoregional progression.
Conclusions: OS and PFS favoured neoadjuvant CarPacRT over OxCapRT. Distant was more common than locoregional progression; therefore, priority should be given to optimising the systemic treatment component.
Clinical trial registration: EudraCT Number: 2012-000640-10; ClinicalTrials.gov: NCT01843829.
Neoadjuvant chemoradiotherapy, Oesophageal cancer, Randomised controlled trial, Surgery, Survival
153-161
Mukherjee, Somnath
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Hurt, Christopher
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Radhakrishna, Ganesh
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Gwynne, Sarah
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Bateman, Andrew
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Gollins, Simon
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Hawkins, Maria A.
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Canham, Joanne
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Grabsch, Heike I.
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Falk, Stephen
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Sharma, Ricky A
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Ray, Ruby
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Roy, Rajarshi
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Cox, Catrin
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Maynard, Nick
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Nixon, Lisette
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Henderson-Smart, David J.
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Maughan, Timothy
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Griffiths, Gareth O.
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Crosby, Tom D.L.
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August 2021
Mukherjee, Somnath
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Hurt, Christopher
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Radhakrishna, Ganesh
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Gwynne, Sarah
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Bateman, Andrew
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Gollins, Simon
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Hawkins, Maria A.
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Canham, Joanne
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Grabsch, Heike I.
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Falk, Stephen
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Sharma, Ricky A
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Ray, Ruby
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Roy, Rajarshi
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Cox, Catrin
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Maynard, Nick
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Nixon, Lisette
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Henderson-Smart, David J.
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Maughan, Timothy
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Griffiths, Gareth O.
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Crosby, Tom D.L.
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Mukherjee, Somnath, Hurt, Christopher, Radhakrishna, Ganesh, Gwynne, Sarah, Bateman, Andrew, Gollins, Simon, Hawkins, Maria A., Canham, Joanne, Grabsch, Heike I., Falk, Stephen, Sharma, Ricky A, Ray, Ruby, Roy, Rajarshi, Cox, Catrin, Maynard, Nick, Nixon, Lisette, Henderson-Smart, David J., Maughan, Timothy, Griffiths, Gareth O. and Crosby, Tom D.L.
(2021)
Oxaliplatin/capecitabine or carboplatin/paclitaxel-based preoperative chemoradiation for resectable oesophageal adenocarcinoma (NeoSCOPE): long-term results of a randomised controlled trial.
European Journal of Cancer, 153, .
(doi:10.1016/j.ejca.2021.05.020).
Abstract
Aim: this is the first randomised study to evaluate toxicity and survival outcomes of two neoadjuvant chemoradiotherapy (CRT) regimens for patients with localised oesophageal adenocarcinoma (OAC) or gastro-oesophageal junction (GOJ) adenocarcinoma. The initial results showed comparable toxicity between regimens and pathological complete response (pCR) rate favouring CarPacRT. Herein, we report survival, progression patterns, and long-term toxicity after a median follow-up of 40.7 months.
Methods: NeoSCOPE was an open-label, UK multicentre, randomised, phase II trial. Eighty-five patients with resectable OAC or GOJ adenocarcinoma, ≥cT3 and/or ≥cN1 (TNM v7), suitable for neoadjuvant CRT, were recruited between October 2013 and February 2015. Patients were randomised to OxCapRT (oxaliplatin 85 mg/m2 on Days 1, 15, and 29; capecitabine 625 mg/m2 orally twice daily on days of radiotherapy [RT]) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 on Days 1, 8, 15, 22, and 29). RT dose was 45 Gy/25 fractions/5 weeks. Both arms received induction chemotherapy (two cycles oxaliplatin 130 mg/m2 on Day 1, capecitabine 625 mg/m2 orally twice daily on Days 1-21) before CRT. Surgery was performed 6-8 weeks after CRT. The primary end-point was pCR. Secondary end-points were toxicity, progression-free survival (PFS), overall survival (OS), and patterns of progression.
Results: eighty-five patients were recruited from 17 UK centres. The median OS was 41.7 months (95% confidence interval [CI] 19.6 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable hazard ratio [HR] = 0.48, 95% CIs: 0.24-0.95, P = 0.035). The median PFS was 32.6 months (95% CIs: 17.1 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable HR = 0.54, 95% CIs: 0.29-1.01, P = 0.053). In both arms, the distant progression was twice as common as locoregional progression.
Conclusions: OS and PFS favoured neoadjuvant CarPacRT over OxCapRT. Distant was more common than locoregional progression; therefore, priority should be given to optimising the systemic treatment component.
Clinical trial registration: EudraCT Number: 2012-000640-10; ClinicalTrials.gov: NCT01843829.
Text
1-s2.0-S0959804921003294-main (1)
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More information
Accepted/In Press date: 8 May 2021
e-pub ahead of print date: 20 June 2021
Published date: August 2021
Additional Information:
Funding:
This work was supported by Cancer Research UK (grant number: C44694/A14614) but they played no role in the study. MH is supported by funding from the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.
Acknowledgements:
The NeoSCOPE trial was sponsored by Velindre University NHS Trust. The Centre for Trial Research at Cardiff University is funded by Cancer Research UK and Health and Care Research Wales. S.M. was funded by NIHR Oxford Biomedical Research Centre and the CRUK Experimental Cancer Medicines Centre, Oxford. The authors thank all the patients who participated in the trial, the doctors, nurses, pathologists, and other members of the MDTs, the radiotherapy team, and the research team from the participating centres. The authors would also like to thank the members of the Trial Management Group. Finally, the authors would like to thank the members of the Independent Data Monitoring Committee and the Independent Trial Steering Committee for their oversight of the trial.
Keywords:
Neoadjuvant chemoradiotherapy, Oesophageal cancer, Randomised controlled trial, Surgery, Survival
Identifiers
Local EPrints ID: 453468
URI: http://eprints.soton.ac.uk/id/eprint/453468
ISSN: 0959-8049
PURE UUID: d1d5ec2e-9f44-44d5-8c80-b419a3eac63f
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Date deposited: 18 Jan 2022 17:35
Last modified: 19 Mar 2024 03:09
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Contributors
Author:
Somnath Mukherjee
Author:
Christopher Hurt
Author:
Ganesh Radhakrishna
Author:
Sarah Gwynne
Author:
Andrew Bateman
Author:
Simon Gollins
Author:
Maria A. Hawkins
Author:
Joanne Canham
Author:
Heike I. Grabsch
Author:
Stephen Falk
Author:
Ricky A Sharma
Author:
Ruby Ray
Author:
Rajarshi Roy
Author:
Catrin Cox
Author:
Nick Maynard
Author:
Lisette Nixon
Author:
David J. Henderson-Smart
Author:
Timothy Maughan
Author:
Tom D.L. Crosby
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