Alderson, D.

Blazeby, J.

Coxon, F.

Crellin, A.

Cunningham, D.

Falk, S.

Goldstein, C.

Grabsch, H.

Griffin, M.

Krysztopik, R.

Langer, R.

Langley, R.

Nankivell, M.

Okines, A.

Pritchard, S.

Stenning, S.

Thompson, J.

RERO DOC Digital Library

abstractsLBA  03 Neoadjuvant chemotherapy for resectable oesophagealand junctional adenocarcinoma: results from the UKMedical Research Council randomised OEO5 trial(ISRCTN 01852072)D. Cunningham1, R. Langley2, M. Nankivell3, J. Blazeby4, M. Griffin5, A. Crellin6,H. Grabsch7, A. Okines8, C. Goldstein3, S. Falk4, J. Thompson9, R. Krysztopik10,F. Coxon11, S. Pritchard12, R. Langer13, S. Stenning3, D. Alderson141Royal Marsden, London, United Kingdom2MRC Clinical Trials Unit at UCL, London, United Kingdom3MRC Clinical Trials Unit at UCL, London, United Kingdom4University of Bristol, Bristol, United Kingdom5Royal Victoria Infirmary, Newcastle, United Kingdom6St James’ Institute of Oncology, Leeds, United Kingdom7Leeds Institute of Cancer Studies and Pathology, Leeds, United Kingdom8Royal Marsden, London, United Kingdom9Birmingham Heartlands Hospital, Birmingham, United Kingdom10Royal United Hospital, Bath, United Kingdom11Northern Centre for Cancer Care, Newcastle, United Kingdom12Wythenshawe Hospital, Manchester, United Kingdom13University of Bern, Bern, Switzerland14Queen Elizabeth Hospital, Birmingham, United KingdomIntroduction: Chemotherapy in addition to surgery improves outcomes ingastro-oesophageal cancer. Both the OEO2 (neoadjuvant) and MAGIC(peri-operative) trials showed statistically significant improvements in overall survivalthough only 55% of patients in the MAGIC trial received post-operative treatment. Weinvestigated whether more neoadjuvant chemotherapy (4 cycles epirubicin/cisplatin/capecitabine (ECX)) compared to a standard approach (2 cycles of cisplatin/5-fluorouracil) would improve outcomes.Methods: A multi-centre, randomised, phase III trial comparing 2 cycles of CF with 4cycles of ECX followed by oesophagectomy with 2-field lymphadenectomy for loweroesophageal and junctional (Types I and II) adenocarcinoma. Primary outcome wasoverall survival (OS); 842 patients (677 deaths) would detect an increase in 3-yearsurvival from 30% to 38% (or 37%) with 82% (or 70%) power with 2α = 5%. Deathsaccrued more slowly than anticipated but the Independent Data MonitoringCommittee considered the data sufficiently robust for release. Secondary outcomesinclude disease-free (DFS) and progression-free survival (PFS), pathological R0resection rate, Mandard grade and quality of life (QoL).Results: From 2005-2011, 897 patients (451 CF, 446 ECX) from 72 UK centres wererandomly allocated (1:1). Baseline characteristics were similar between the groups(overall, male 90%, median age 62 (IQR 56-67), staging included PET 60%, T3 N022%, T3 N1 65%). 96% CF received 2 cycles, 89% ECX > 3 cycles. Grade 3/4 toxicitywas lower with CF (30% v 47% p < 0.001). Of those patients having a resection R0 rateswere CF 60%, ECX 66% with a Mandard grade ≤3 achieved in CF 15% v ECX 32%with 3% and 11% achieving complete response. Post-operative complications weresimilar (CF 57%, ECX 62%) as were deaths at 30 (CF 2%, ECX 2%) and 90 dayspost-surgery (CF 4%, ECX 5%). PFS and DFS favoured ECX, hazard ratio (HR, 95%CI) PFS 0.86 (0.74-1.01), DFS 0.88 (0.75-1.03). HR for OS was 0.92 (0.79-1.08,p = 0.3017) based on 315 CF and 298 ECX deaths, with similar 3 year survival rates CF39% (35-44%) vs ECX 42% (37-46%). Exploratory subgroup analyses suggested that N0patients may benefit from ECX, HR for OS was 0.68 (0.47-0.97). There were noclinically important differences in QoL (global QoL and oesophageal cancer specificdomains from the EORTC QLQ-C30 and QLQ-OES18 questionnaires), eitherpre-operatively or 3-months post-operatively.Conclusion: There is some evidence of a benefit from the prolonged ECX regimen,in terms of PFS, DFS and tumour regression at resection, but this does nottranslate into a survival benefit. Ongoing translational work is aimed at identifyingsubsets of patients that might benefit from the triplet anthracycline containingregimen.© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.For permissions, please email: journals.permissions@oup.com.abstractsAnnals of Oncology 26 (Supplement 4): iv117–iv121, 2015doi:10.1093/annonc/mdv262.3

LBA-03Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072)

http://doc.rero.ch/record/299314/files/mdv262.03.pdf

LBA-03Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072)

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library