Lessons learnt from scoring adjuvant colon cancer trials and meta-analyses using the ESMO-Magnitude of Clinical Benefit Scale V.1.1

ESMO Open

article

Daan Geert Knapen¹  Nathan I. Cherny²  Panagiota Zygoura³  Nicola Jane Latino⁴  Jean-Yves Douillard⁴  Urania Dafni⁵  Elisabeth G.E. de Vries¹  Derk Jan de Groot¹ 

[1] Medical Oncology, University Medical Centre Groningen;Medical Oncology, Shaare Zedek Medical Center;Statistics, Frontier Science Foundation-Hellas;ESMO-MCBS Working Group, European Society for Medical Oncology;Nursing, National and Kapodistrian University of Athens;University of Athens

关键词: ESMO-MCBS;    early colon cancer;    toxicity;    adjuvant chemotherapy;    quality of life;   

DOI  :  10.1136/esmoopen-2020-000681

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Form 1 of the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale(ESMO-MCBS) serves to grade therapies with curativeintent. Hitherto only few trials with curative intenthave been field tested using form 1. We aimed toevaluate the applicability of the scale and to assess thereasonableness of the generated scores in early coloncancer, in order to identify shortcomings that may berectified in future amendments.Methods Adjuvant studies were identified in PubMed,Food and Drug Administration and European MedicinesAgency registration sites, as well as ESMO and NationalComprehensive Cancer Network guidelines. Studiesmeeting inclusion criteria were graded using form 1 of theESMO-MCBS V.1.1 and field tested by ESMO ColorectalCancer Faculty. Shortcomings of the scale were identifiedand evaluated.Results Eighteen of 57 trials and 7 out of 14 metaanalyses identified met criteria for ESMO-MCBS V.1.1grading. In stage III colon cancer, randomised clinicaltrials and meta-analyses of modulated 5-fluorouracil(5-FU) based chemotherapy versus surgery scored ESMOMCBS grade A and randomised controlled trials (RCTs)and meta-analyses comprising oxaliplatin added to this5-FU backbone showed a more modest additional overallsurvival benefit (grade A and B). For stage II colon cancer,the findings are less consistent. The fluoropyrimidinetrials in stage II were graded ‘no evaluable benefit’ but themost recent meta-analysis demonstrated a 5.4% survivaladvantage after 8 years follow-up (grade A). RCTs and ameta-analysis adding oxaliplatin demonstrated no addedbenefit. Exploratory toxicity evaluation and annotationwas problematic given inconsistent toxicity reporting andlimited results of late toxicity. Field testers (n=37) reviewedthe scores, 25 confirmed their reasonableness, 12 foundthem mostly reasonable. Moreover, they identified theinability of crediting improved convenience in noninferiority trials as a shortcoming.Conclusion Form 1 of the ESMO-MCBS V.1.1 providedvery reasonable grading for adjuvant colon cancer studies.

【 授权许可】

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