1435O_PR - Comparison of the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) in Clinical Trials Supporting US Food and D...

Date 11 September 2017
Event ESMO 2017 Congress
Session Public health policy and health economics
Topics Bioethics, Legal, and Economic Issues
Presenter Consolacion Molto Valiente
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors C. Molto Valiente1, A. Tibau1, A. Ocana Fernandez2, A. Templeton3, L. del Carpio Huerta1, J. Del Paggio4, A. Barnadas1, C. Booth5, E. Amir6
  • 1Oncology Department, Hospital de la Santa Creu i Sant Pau and Universitat Autònoma de Barcelona, 8026 - Barcelona/ES
  • 2Medical Oncology Department And Translational Research Unit, Albacete University Hospital, Albacete/ES
  • 3Department Of Medical Oncology, St Claraspital and Faculty of Medicine, University of Basel, Basel/CH
  • 4Division Of Cancer Care And Epidemiology, Queen’s University Cancer Research Institute, Kingston/CA
  • 5Departments Of Oncology And Public Health Sciences, Queen’s University Cancer Research Institute, K7L 3N6 - Kingston/CA
  • 6Division Of Medical Oncology & Hematology, Department Of Medicine, Princess Margaret Cancer Centre and the University of Toronto, M5G 2M9 - Toronto/CA



The Orphan Drug Act provides incentives to manufacturers to develop drugs for rare diseases. The ESMO-MCBS is a validated tool, aimed at quantifying the clinical benefit for cancer drugs. Here, we compare the characteristics of clinical trials leading to approval by the FDA of orphan and non-orphan drugs and apply the ESMO-MCBS thresholds for meaningful clinical benefit.


We searched the Drugs@FDA website to identify anticancer drugs approved between January 2006 and December 2016. These were then categorized as orphan or non-orphan drugs as determined by the FDA. For each drug, we subsequently collected data on clinical trial design and methodology and compared these between orphan and non-orphan drugs. For drugs supported by randomized controlled trials (RCTs), we applied a ESMO-MCBS grade. Comparisons were performed using Mann Whitney U or Chi squared tests.


Of the 137 studies included, 109 (80%) were RCTs. These led to the approval of 63 individual drugs for 118 indications. Among these indications, 54 (46%) received orphan drug designation. Compared to non-orphan drugs, trials supporting orphan drugs approval had a smaller sample size (median 369 vs 687, P=.001), were less likely to evaluate experimental cytotoxic chemotherapy or endocrine therapy than targeted therapy (8% vs 21%, P=.005) were less often randomized (73% vs 86%; P=.047) and were more likely to assess intermediate endpoints rather than overall survival (71% vs 51%, P=.01). A similar proportion of orphan and non-orphan drugs approved for palliative use met the ESMO-MCBS threshold for meaningful benefit (29% vs 27%; P=.86). There were too few studies performed in the curative setting (n = 7) to perform statistical testing.


Compared with trials used to approve non-orphan cancer drugs, trials for orphan drugs are smaller, more likely to explore experimental biological therapies, use single-arm trials and intermediate end points. A similarly low proportion of approved orphan and non-orphan drugs meet the ESMO-MCBS threshold for meaningful benefit.

Clinical trial identification

Not applicable

Legal entity responsible for the study





All authors have declared no conflicts of interest.