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- R. Giuliani
- C. Uyl-De Groot
1435O_PR - Comparison of the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) in clinical trials supporting US Food and Drug Administration (FDA) approval of orphan vs. non-orphan drugs (ID 1550)
- C. Molto Valiente
Abstract
Background
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.
Methods
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.
Results
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,
Conclusions
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
None
Funding
None
Disclosure
All authors have declared no conflicts of interest.
1436O_PR - How to assess a cancer therapy? Feedback from the French HTA body on the ESMO-MCBS (ID 2429)
- M. Grande
Abstract
Background
Concerns about cancer drug affordability explain the need to base reimbursement and pricing decisions on clinical added value (CAV). A special attention is given to the CAV assessment by Health Technology Assessment (HTA) bodies. In 2015, The European Society for Medical Oncology (ESMO) published the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), to assess CAV of drugs in solid tumors. For more than 20 years, the French National Authority for Health (HAS), which is responsible for HTA, assesses CAV on a 5-point scale from I (major CAV) to V (no CAV). While the HAS CAV scale is used for pricing, it is not used for reimbursement decision. The opportunity for HAS to use the ESMO scale should be further explored.
Methods
To compare both the ESMO-MCBS CAV assessment and that done by HAS, we reviewed the 77 trials that were tested by the ESMO Task Force in its 2015 publication.
Results
Of the 77 trials tested using ESMO-MCBS, 59 were also appraised by HAS, 16 were not assessed and 2 are still under assessment by the HAS. In about 39% (23) of the 59 indications considered, the HAS CAV appraisal was consistent with the ESMO ranking. When an inconsistency was observed (36, 61%), the HAS CAV assessment was systematically more strict. No indication had a higher score than the ESMO evaluation under the HAS evaluation. In 37 indications (62%), the ESMO-MCBS indicated a substantial improvement in CAV. Of these, 48% (13/37) obtained a similar ranking by the HAS. Thirteen indications were downgraded for toxicity by the HAS while only two were downgraded for that criteria under the ESMO-MCBS. The HAS gave an unfavorable opinion for reimbursement for 4 indications that obtained the lowest scores on ESMO-MCBS.
Conclusions
In most cases, disparities between the ESMO-MCBS and the HAS assessment of CAV were observed. The HAS appears to be more demanding in its appraisals, which are mainly based on the level of evidence, comparator relevance, transposability of the results and safety. In the case of a health technology evaluation, the possibility of an unfavorable opinion for drug access should be added in the ESMO-MCBS. As CAV impacts drug prices, the use of the ESMO-MCBS might have led to an increase in French cancer expenses. Nevertheless, the ESMO-MCBS provides an objective tool for HTA bodies to rate CAV.
Legal entity responsible for the study
HAS
Funding
None
Disclosure
All authors have declared no conflicts of interest.
1437O_PR - Clinical benefit of randomized controlled trials (RCT) supporting US Food and Drug Administration (FDA) conversion from accelerated to full approval (ID 1743)
- M. Borrell Puy
Abstract
Background
Accelerated approval (AA) regulations were established by the US FDA to improve access to drugs for life-threatening diseases. Pharmaceutical companies must confirm efficacy in post-approval trials as predicted by the surrogate endpoint. The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated and reproducible tool to assess the magnitude of clinical benefit from drugs for solid tumors. Here, we evaluate confirmatory RCTs supporting conversions from AA to regular approval (RA) and their association with ESMO defined thresholds for meaningful clinical benefit.
Methods
We searched the Drugs@FDA website to identify anticancer drugs that had received AA from January 2000 to December 2016 and to assess the status regarding conversion to full approval. Drug labels and reports of post-approval trials supporting conversion to RA were reviewed and study characteristics, efficacy, toxicity and quality of life outcomes were collected. For RCTs ESMO-MCBS grades were applied. Meaningful clinical benefit was defined as a grade of A or B for trials of curative intent and 4 or 5 for those of palliative intent.
Results
Of the 37 new indications granted AA, 17 (46%) were subsequently converted to RA based on 17 RCTs. The median time between AA and RA of oncology drugs was 3.1 years (range = 1.02–7.6). Two confirmatory trials (5%) failed to show clinical benefit. Confirmatory trials were still not completed for 18 (49%) indications; among these, the three longest intervals since AA up to the December 2016 cut-off date were 6.6, 5.9 and 2.3 years. ESMO-MCBS could be applied to 16 RCTs and 11 (69%) met the ESMO-MCBS clinically meaningful benefit threshold (100% of adjuvant trials and 58% of palliative trials).
Conclusions
Two thirds of RCTs supporting FDA conversion from accelerated to full approval of anticancer therapies meet the threshold for clinically meaningful benefit. AA indications should not be on the market for unacceptably prolonged intervals before confirmatory trials are completed.
Clinical trial identification
Not applicable
Legal entity responsible for the study
Hospital de la Santa Creu i Sant Pau
Funding
None
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 1435O, 1436O and 1437O (ID 5890)
- C. Uyl-De Groot
1438O_PR - Report on ESMO/SIOPE European Landscape project key results: Mapping the status and needs in AYA cancer care (ID 1018)
- E. Saloustros
Abstract
Background
Adolescents and young adults (AYA) are a distinct group at the interface between children’s and adult’s cancer services that require specific clinical management and care. This survey explored health care providers' practice patterns, knowledge and available services regarding AYA cancer care.
Methods
A link to an online survey was sent by e-mail to all members of ESMO and SIOPE, ESMO national representatives and circulated to several European oncology groups. The questions covered the following topics: demographics, education and access to specialized care for AYA, research and supportive care opportunities, as well as demands for further education. Contingency tables for each question were calculated and were further explored by sub region in Europe using chi-squared and Fisher’s exact test.
Results
323 responses were collected from all countries across the world. We report the results from the 266 practitioners responding from Europe. Over two-thirds report that they: Do not have access to specialized centers for AYA with cancer (67%), Are not aware of any cancer research studies or clinical trials focused on AYA (69%), Have no access to a specialist cancer service for late effects management (67%). The majority of the professionals responding are able to refer AYA patients to professional psychological support and specialized social workers. However more than half report no access to an age-specialized nurse, specialized AYA education or a learning mentor. Furthermore, a substantial number of professionals report that their AYA patients do not have access to fertility specialists (38%), rising to 76% in Eastern Europe (EE). The lack of specialized AYA care was more profound for practitioners from EE and South Eastern European (SE) countries.
Conclusions
Less than one half of European health-care providers who treat AYA with cancer have access to specialized centers and research initiatives for this group of patients with special needs. This survey revealed important under-provision and inequity of AYA cancer care across Europe. Improving care using education and research focused on AYA is a growing priority for both ESMO and SIOPE.
Clinical trial identification
N/A
Legal entity responsible for the study
ESMO, SIOPE
Funding
ESMO, SIOPE
Disclosure
D. Stark: Receipt of research grant income in AYA cancer from the National Institute for Health Research, Cancer Research UK, the Teenage Cancer Trust and research support from Pharmamar Inc and Astra- Zeneca Inc. F.A. Peccatori: Fees from Roche, Astra Zeneca, Clovis and Ipsen. S. Bielack: Fees for participation at Advisory Boards in Pfizer, Bayer, Lilly, Novartis, Isofol. All other authors have declared no conflicts of interest.
1439O_PR - Paediatric radiation therapy across Europe: A European questionnaire survey supported by the SIOPe, ESTRO, PROS and several national paediatric hematology-oncology societies (NAPHOS) (ID 2409)
- C. Demoor-goldschmidt
Abstract
Background
Increased focus has been made to improve the quality of care and access to European trials in paediatric oncology. Information about paediatric radiotherapy (Ped-RT) throughout Europe is not widely available. The aim of this study was to provide an overview of resources and organization for Ped-RT.
Methods
Experts in Ped-RT oncology were invited by email to complete a 21-point questionnaire.
Results
Sixty-nine answers from 24 countries (7 centres with proton) were collected and 16 centres were visited. A minority of radiation oncologists (11.74%) treat only children, which is in contrast with paediatric oncologists (93.44%) or surgeons (71.67%) who are more often dedicated. In 5 countries, ped-RT is centralized in one centre. Access to ped-RT formations is unequal throughout Europe even if everyone agrees with the fact that specific knowledges are needed. Regarding the techniques, 12% use sometimes, meaning for some patients, 2D- conventional radiotherapy, 4% still use Cobalt and 15% never or rarely use IMRT (Intensity Modulated Radiotherapy), 64% use hypofractionated treatments, defined as at least 3Gy per fraction and 32% when considering 5 Gy or more. Eighty-four percent have access to paediatric devices for personalized immobilization. Radiation treatments can be easily delivered under anaesthesia in 75% of the centres if necessary, or under hypnosis in 9% of centres (2 countries). The environment is mostly adapted to children, with dedicated waiting area (47%), patient information (83%), gifts (98%), the possibility to listen to music or songs (93%) or watch cartoons (12%).
Conclusions
This survey provides quantitative data demonstrating the current healthcare inequalities for children and adolescents who need radiotherapy in Europe. Nevertheless, an effort to guarantee a treatment of quality with the local environment has been pointed out.
Clinical trial identification
not applicable
Legal entity responsible for the study
C. Demoor-Goldschmidt
Funding
None
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 1438O_PR and 1439O_PR (ID 5891)
- P. Bruzzi