ДУ "Інститут урології
імені академіка О.Ф.Возіанова"

Dear colleague,

Please find below three Press Releases relating to studies on health economics at ESMO 2016 today.

• First feasibility study of the ESMO-MCBS scale in rare tumour entities

• Single-arm trials for early access to cancer drugs

• Financial difficulties linked to worse outcomes from cancer treatment

PRESS RELEASE

EMBARGOED until 10 October 2016, 8:15 hours (CEST)

First feasibility study of the ESMO-MCBS scale in rare tumour entities

LUGANO-COPENHAGEN, 10 October 2016 – The results of the first study analysing the application of the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) in a real-life context for rare tumour entities, were announced today at the ESMO 2016 Congress in Copenhagen¹.  

The ESMO-MCBS is a new tool to quantify the clinical benefit of a certain drug for the treatment of cancer and its application in daily clinical practice. It was first evaluated on common tumour entities by one of Europe’s largest cancer centres, the Medical University of Vienna (MUV), which also conducted this new study.

Dr Barbara Kiesewetter at MUV states, “We assessed data on neuroendocrine tumors (NET), glioblastoma, sarcomas, thyroid, pancreatic, ovarian, head/neck and urothelial cancers. Data was analysed in a three-step approach: we collected data on regimens in daily use at the MUV, then analysed the data with the ESMO-MCBS as our second step and finally we evaluated and discussed the data in terms of clinical feasibility and practicability in daily practice."

“We noted a phenomenon whereby the ESMO-MCBS particularly highlights the clinical benefit to be expected of new immunomodulatory drugs. This was also observed in our field testing on common tumour entities and may help us to implement these treatments in daily practice in the near future.  We are particularly excited that new data on check point inhibitors for rare entities is due to be available soon. For example, in head and neck cancers, the CHECKMATE141 data currently scores for an ESMO-MCBS score of 3 (field testing) based on available results² but might improve to an even stronger recommendation with more mature survival data,” she continued.

“The practicability of applying the ESMO-MCBS is somewhat limited for very rare tumours, for example sarcoma and glioblastoma, due to a lack of randomized data. However, the ESMO-MCBS was applicable in most situations where controlled trials were available such as the data on salvage treatment with pazopanib for soft tissue sarcoma achieving a score of 3 based on a significant progression free survival (PFS) gain of 3 months in comparison to 1.6 months in the placebo arm³.

“For sarcomas, practicability of ESMO-MCBS was limited due to a lack of trials in many indications. However, the ESMO-MCBS was useful whenever randomized data were available. For example, the ESMO-MCBS score of 4 clearly underlines the clinical benefit achieved by adding dacarbazine to gemcitabine in pre-treated soft tissue sarcoma (4). This is in line with our clinical experience and supports further use of the ESMO Magnitude of Clinical Benefit Scale,”  Kiesewetter explained.

The ESMO-MCBS has been designed to assess the therapeutic benefit of drugs registered for the treatment of cancer.  It considers the predefined primary and secondary study endpoints:  overall survival and progression-free survival in terms of absolute gain and lower end of the 95% confidence interval of the corresponding hazard ratio and quality of life or toxicity respectively. Data of the new treatment is then analysed with respect to the duration of response or survival in the control arm, which has to be entered in corresponding forms and results in a clinical benefit ranking.

 “We found that the ESMO-MCBS is a helpful tool for clinical practice in rare tumours, as well as for common tumour entities, if randomized data is available. It supports treatment decisions based on the expected clinical benefit. It is very simple to use and we feel that it is going to prove to be a very important tool for daily clinical practice based on our study results. Clinicians can go back to the data when considering new treatments and use the ESMO-MCBS online to analyse what can be expected from a new approach,” concluded Dr Kiesewetter.

-END-

Notes to Editors

References

¹ Abstract 1364O_PR “The ESMO-Magnitude of Clinical Benefit Scale (MCBS) in rare tumour entities: A real life experience at the Medical University Vienna” will be presented by Barbara Kiesewetter during the Proffered Paper session, Public health and health economics on Monday 10 October 2016, 16:30 to 18:00 (CEST) in Room Oslo.

² Ferris RL, Blumenschein GR, Fayette J, et al. Further evaluations of nivolumab (nivo) versus investigator’s choice (IC) chemotherapy for recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CheckMate 141. 2016 ASCO Annual Meeting J Clin Oncol 34, 2016 (suppl; abstr 6009)

³ Van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 Trial. Lancet. 2012;379(9829):1879-86.

⁴ García-Del-Muro X, López-Pousa A, Maurel J, et al. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study.J Clin Oncol. 2011;29(18):2528-33.

Disclaimer

This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .

About the European Society for Medical Oncology

ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.

Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.

www.esmo.org

Abstract for 1364O_PR

The ESMO-Magnitude of Clinical Benefit Scale (MCBS) in rare tumor entities: A real life experience at the Medical University Vienna

B. Kiesewetter, M. Raderer, C. Marosi, T. Brodowicz, G. Prager, M. Krainer, T. Fuereder, G.J. Locker, C.C. Zielinski
Medicine I, Clin. Div. of Oncology and Comprehensive Cancer Center, Medizinische Universitaet Wien (Medical University of Vienna), Vienna, Austria

Background: The ESMO-MCBS is a new tool to quantify the clinical benefit of a certain drug for the treatment of cancer. Recently, we have evaluated the practicability of the MCBS in daily practice of treating common tumor entities at our center. However, to date there is no experience of using the MCBS for rare tumors.

Methods: This study analyses the feasibility of the MCBS for rare tumor entities at the Clinical Division of Oncology, Medical University Vienna. We developed a 3-step approach to address this question. First, we retrospectively collected data to gain an overview on treatments in regular use. Second, we scored data with the MCBS, and third, evaluated results with the corresponding program directorships to assess the feasibility in a real-life context.

Results: We assessed data on neuroendocrine tumors (NET), glioblastoma, sarcomas, thyroid-, pancreatic-, ovarian-, head/neck- and urothelial cancer. The following results were obtained: 1.) NET and thyroid cancer: Recently published trials are comparable in design and efficacy and the MCBS scores are consistent with the clinical benefit seen in practice. However, the MCBS added little information on the question of optimal sequencing except for differentiated thyroid cancer where prior treatment (TKI or not) suggests an algorithm. 2.) Pancreatic cancer: only two major 1st-line trials are currently available and a direct comparison is difficult due to diverging populations. 3.) Sarcomas: MCBS reflects well the situation of GIST and was useful for randomized data on non-GIST sarcoma, but MCBS practicability was limited in rare subtypes due to a lack of controlled trials. 4.) Ovarian cancer: the MCBS supports the use of bevacizumab in high-risk patients. This is in line with our experience. To date, there is only limited data for glioblastoma, head/neck- and urothelial cancer. However, if randomized trials were available, the MCBS-rating supported clinical decisions particularly for novel compounds. A broad selection of analyzed data will be presented at the meeting.

Conclusions: The MCBS is a helpful tool for clinical practice in rare tumors, if randomized data are available. It supports treatment decisions based on the expected clinical benefit.

Legal entity responsible for the study: Department of Medicine I, Medical University of Vienna

Funding: Department of Medicine I, Medical University of Vienna

Keywords: quality control, rare tumor, clinical benefit, ESMO-MCBS

PRESS RELEASE

EMBARGOED until 10 October 2016, 8:15 hours (CEST)

Single-arm trials for early access to cancer drugs

LUGANO-COPENHAGEN, 10 October, 2016 –Although randomised clinical trials (RCTs) remain the gold standard for evaluating the benefit/risk of cancer drugs, single-arm trials (SATs) can provide invaluable opportunities to speed up cancer drug development and approval, in particular for drugs with dramatic activity and strong biological rationale in small populations with high unmet need, Dr. Jorge Martinalbo, Scientific Officer at the European Medicines Agency (EMA) reported at the ESMO 2016 Congress today¹. “Drug approval requires demonstration of a positive benefit/risk ratio, usually based on evidence from randomised clinical trials (RCTs). Nevertheless, in certain instances such as very rare cancers or molecular subgroups, or when preliminary evidence shows dramatic efficacy in settings of high unmet medical need, RCTs may not be strictly required for regulatory approval,” he said.

There is limited regulatory guidance about the circumstances under which SATs can provide sufficent evidence for EU authorisation. The EMA and ESMO have recently started a collaboration to define evidence requirements that can satisfy market access decision-makers, patients and clinicians, and facilitate access to innovative cancer drugs.

As part of this effort, Dr Martinalbo analysed the role of SATs in 263 applications for initial approval or indication extension for cancer drugs reviewed by EMA between 1995-2014. Martinalbo explained that: “around 20% of cancer drug approvals in the EU in the last 20 years were based on evidence from SATs, and more than half of the initial authorisations for haematological malignancies. Almost one-third of targeted drugs used in biomarker-restricted populations were approved on the basis of response rate. Perhaps surprisingly, regulatory review times and success rates for initial approvals based on SATs are similar to those based on RCTs. Altogether this reflects the flexibility of regulatory requirements for approval, supported by early access tools like conditional and exceptional circumstances authorisations used in almost half of the initial approvals based on SATs.”

There are, however, further decisions at national and regional level before patients can have access to new cancer drugs, that take into account economic criteria². “The increased uncertainty inherent to evidence from uncontrolled trials can pose challenges to subsequent health technology assessment (HTA) and price and reimbursement decisions at a national level, potentially compromising effective access to patients,” Martinalbo explained.

This was one of the key topics in a recent workshop³ jointly organised by the EMA and ESMO, where a wide range of stakeholders including clinical scientists and drug developers in academia and pharmaceutical industry, regulators, patient representatives and HTA bodies discussed the evidence requirements and particular challenges for cancer drug approval and reimbursement decisions based on SATs.

“The workshop allowed us to realise the diversity of views and the challenges in developing an evidence framework that could satisfy all stakeholders. We identified certain methodological areas such as innovative endpoints, external controls and basket trials which provide opportunities to improve evidence generation, and together with ESMO we are currently establishing core groups to further elaborate on them. We understand that approval decisions affect everyday clinical practice, and the workshop clearly showed us the immense opportunities offered by a close collaboration with ESMO,” concluded Martinalbo.

Commenting on the abstract, Dr Denis Lacombe, EORTC Director General who has a vast experience in clinical research, said: “The retrospective study performed by European regulators analysing the role played by SATs between 1994 and 2015 brings light to the actual regulatory impact of SATs in Europe. It certainly illustrates the evolution of regulatory sciences as new designs and new end-points challenge the methodology of clinical research, now based on well documented knowledge on both mechanisms of action of new drugs and biology of diseases. However, robustness of databases on which new treatments are made available to cancer patients should not be compromised.”

Dr Lacombe explained that: “Randomised clinical trials and SATs can’t be considered alternatives to each other. SATs bring less robust data to patients, with ethical and societal implications, further impacting HTA and reimbursement decisions. In absence of benchmarking traditionally provided by RCT, the decision process remains uncertain. In addition, there is no justifiable reason why certain groups of patients would be treated based on less robust data.”

Dr Lacombe concluded: “Clinical researchers must develop new solutions that span from proof of concept to effectiveness, constantly taking the challenges to bring solid evidence to patients and not too easily compromising towards easier routes such as SATs which should be limited to situations where strong biological evidence emerges in absence of relevant existing therapeutic strategies and/or unmet needs. Discussing SATs outside of a complete transformation of clinical research may jeopardise appropriate recognition of SATs where they may be useful and is certainly a disservice to patients.”

-END-

Notes to Editors

References

¹ Abstract 1362O_PR “Single-arm trials for cancer-drug approval and patient access,” will be presented by Dr Jorge Martinalbo during the Proffered Paper Session, Public health and health economics on Monday 10 October 2016, 16:30 to 18:00 (CEST) in Room Oslo.

² Martinalbo et al. Early market access to drugs in the EU. Ann Oncol (2016) 27 (1): 96-105.

³ EMA-ESMO Single-arm trials in cancer drug evaluation workshop slides: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2016/05/event_detail_001285.jsp&mid=WC0b01ac058004d5c3

Disclaimer

This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .

About the European Society for Medical Oncology

ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.

Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.

www.esmo.org

Abstract for 1362O_PR

Single-arm trials for cancer drug approval and patient access

J. Martinalbo1, J. Camarero2, B. Delgado-Charro1, P. Démolis3, J. Ersbøll4, P. Foggi5, B. Jonsson6, D. O'Connor7, F. Pignatti8

1R&D Support Division, European Medicines Agency (EMA), London, UK, 2Oncology drug evaluation, Spanish Agency for Medicines and Healthcare Products (AEMPS), Madrid, Spain, 3Strategy, French National Agency for Medicines and Health Products Safety (ANSM), Paris, France, 4Licensing, Danish Medicines Agency (DKMA), Copenhagen, Denmark, 5Licensing, Italian Medicines Agency (AIFA), Rome, Italy, 6Licensing, Swedish Medical Products Agency (MPA), Uppsala, Sweden, 7Licensing, Medicines and Healthcare products Regulatory Agency (MHRA), London, UK, 8Oncology, Haematology and Diagnostics, European Medicines Agency (EMA), London, UK

Background: Single-arm trials (SATs) can provide an invaluable opportunity to speed up cancer drug development and approval, typically for drugs with dramatic activity in small populations with high unmet medical need. However, the inherent higher uncertainty about the drug’s safety and efficacy and challenges in assessing added therapeutic value by health technology assessment (HTA) bodies and payers can negatively impact effective patient access, which shows significant variability across EU countries. Regulatory guidance addressing the SAT-specific regulatory challenges is currently limited, and harmonised value criteria for cancer drugs approved on the basis of SATs are still lacking. In practice, there appear to be divergent views across stakeholders on what might constitute compelling efficacy vs. unmet need, and variable tolerance for uncertainty.

Methods: The European Medicines Agency (EMA) is addressing these challenges, in collaboration with relevant stakeholders, including clinicians, patients, developers, regulators and HTAs/payers.

Results: Results will be presented from a comprehensive research project on EMA’s experience with SATs in approvals and scientific advice, but also analysing value perception by HTAs and effective access in major EU markets.

Conclusions: The conclusions will identify areas that could benefit from further regulatory guidance, with regard to methodology (endpoints, novel trial designs, external controls, molecularly annotated registries, supportive data, Bayesian approaches) and policy frameworks (magnitude of benefit vs. unmet need, uncertainty regarding efficacy, safety and cost-effectiveness and post-approval confirmatory evidence), with the ultimate aim of increasing predictability of the 'requirements' for patient access decisions by regulators and HTAs/payers, and facilitating early access of promising drugs to patients in need.

Legal entity responsible for the study: N/A

Funding: European Medicines Agency

Disclosure: All authors have declared no conflicts of interest.

Keywords: drug development, single arm trial, early access

PRESS RELEASE

EMBARGOED until 10 October 2016, 8:15 hours (CEST)

Financial difficulties linked to worse outcomes from cancer treatment

LUGANO-COPENHAGEN, 10 October, 2016 – Financial difficulties can significantly impact a cancer patient’s quality of life during treatment and may even increase their risk of death, according to the results of a pooled analysis presented at the ESMO 2016 Congress in Copenhagen.

“Financial difficulties may impact the outcome for cancer patients even in countries where the national public health system covers most of the expenses, and therefore, it is our mission to understand what are the determinants of such difficulties and whether some of them may be actionable,” said principal investigator Dr. Francesco Perrone, director of the Unità Sperimentazioni Cliniche at the National Cancer Institute of Naples, Italy.

Researchers pooled data from 16 prospective multicenter trials in Italy involving a total of 3670 patients with either lung, breast or ovarian cancer, which included the EORTC quality of life C30 questionnaire. Question 28 of this questionnaire asks patients to rate financial difficulties related to their disease or treatment on a scale from ‘not at all’ to ‘very much’.

The analysis showed that financial burden – defined as any financial difficulty reported at baseline – was present in 26% of patients at baseline, and was associated with a 35% greater risk of a worse global quality-of-life response (p = 0.009).

Furthermore, financial toxicity, defined as a worsening of the financial score in subsequent questionnaire, was observed in 22.5% of the 2735 who filled out a subsequent questionnaire, and was associated with a 20% increase in the risk of death (p = 0.007).

Perrone said the researchers had expected to find an impact on quality of life from financial hardship, but were surprised to see that worsening financial problems during treatment was associated with a higher risk of death over the course of treatment.

“The size of this impact is moderate but not negligible; it is similar in size to the effect that pushed some new drugs into the market over the last twenty years,” Dr. Perrone said.

While pointing out that it was not possible to completely disentangle financial toxicity from a worsening of a patient’s clinical condition and disease progression, Perrone said the results from this analysis reflect those observed in similar analyses conducted in the US.

“Based on common sense, we oncologists should pay attention  to the social status and economic possibilities of our patients and try to advise them regarding their rights in terms of public support and respect due to their condition,” Perrone said.

Commenting on the study, Dr Nathan Cherny from the Shaare Zedek Medical Center in Jerusalem, said the study demonstrates that even when patients do not have to pay – for example, when they are participating in a clinical trial – a significant number of them enter treatment with some degree of financial burden.

“These findings underscore that even in the absence of payment or co-payment of medications, being ill with cancer often has severe and progressive financial impact on patients and their families,” Dr Cherny said.

“In the absence of substantial supports and benefits, this may not only compromise quality of life but also patient outcomes.”

-END-

Notes to Editors

References

¹ Abstract LBA 1020O_PR ‘The effect of financial difficulties on clinical outcomes in Italian cancer patients: a pooled analysis of 16 academic prospective clinical trials’ will be presented by Dr. Francesco Perrone during the Proffered Paper session, Public health and health economics, on Monday 10 October 2016, 16:30 to 18:00 (CEST) in Room Oslo.

Disclaimer

This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO and ESMO cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct .

About the European Society for Medical Oncology

ESMO is the leading professional organisation for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries, we are the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment.

Founded in 1975, ESMO has European roots and a global reach: we welcome oncology professionals from around the world. We are a home for all oncology stakeholders, connecting professionals with diverse expertise and experience. Our educational and information resources support an integrated, multi-professional approach to cancer treatment. We seek to erase boundaries in cancer care as we pursue our mission across oncology, worldwide.

www.esmo.org

Abstract for 1020O_PR

The effect of financial difficulties on clinical outcomes in Italian cancer patients: A pooled analysis of 16 academic prospective clinical trials

F. Perrone1, C. Jommi2, M. Di Maio3, A. Gimigliano1, C. Gridelli4, S. Pignata5, F. Ciardiello6, F. Nuzzo7, A. de Matteis7, L. Del Mastro8, J. Bryce1, G. Daniele1, A. Morabito9, M.C. Piccirillo1, G. Rocco9, L. Guizzaro10, C. Gallo10
1Clinical Trial Unit, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Naples, Italy, 2Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara, Italy, 3Oncology, Università degli Studi di Torino, Turin, Italy, 4Medical Oncology, Azienda Ospedaliera S. Giuseppe Moscati, Avellino, Italy, 5Urogynecology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Naples, Italy, 6Oncology, Second University of Naples, Naples, Italy, 7Senology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Naples, Italy, 8Medical Oncology, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy, 9Thoracic Oncology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Naples, Italy, 10Statistica medica, AOU Seconda Università degli Studi di Napoli (AOU-SUN), Naples, Italy

Background: Cancer may cause financial difficulties, particularly when co-payment is required for antineoplastic treatment. The impact of financial difficulties in countries with public health systems is unknown. We investigated the prognostic value of financial difficulties on clinical outcomes of cancer patients enrolled in academic clinical trials performed within the Italian public health system.

Methods: Data were pooled from 16 prospective multicentre trials in lung, breast or ovarian cancer, using the EORTC quality of life (QOL) C30 questionnaire. Question 28 scores financial difficulties related to disease or treatment from 'not at all' to 'very much'. We defined financial burden (FB) as any financial difficulty reported at baseline questionnaire, and financial toxicity (FT) as score worsening in a subsequent questionnaire. We investigated (i) the prognostic role of FB on clinical outcomes (survival, global QOL response [questions 29/30] and the occurrence of severe toxicity), and (ii) the effect of FT on survival using a landmark time of 4.5 months. Multivariable analyses were performed using logistic regression models or the Cox model adjusting for trial, gender, age, region, period of enrolment, baseline global QOL and, where appropriate, FB and global QOL response. Results are reported as odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI).

Results: At baseline, 26% of 3670 study patients reported FB, significantly correlated with worse baseline global QOL. FB was not associated with risks of death (HR 0.94, 95%CI: 0.85-1.04, p=0.23) and severe toxicity (OR 0.90, 95%CI: 0.76-1.06, p=0.19) but was predictive of a higher chance of worse global QOL response (OR 1.35, 95%CI: 1.08-1.70, p=0.009). During treatment, 2735 patients filled in subsequent questionnaires and 616 (22.5%) developed FT that was significantly associated with an increased risk of death (HR 1.20, 95%CI: 1.05-1.37, p=0.007). Several sensitivity analyses confirmed these findings.

Conclusions: Even in a public health system, financial difficulties are associated with relevant cancer patients outcomes like QOL and survival.

Legal entity responsible for the study: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G.Pascale, IRCCS, Naples

Funding: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G.Pascale, IRCCS, Naples

Disclosure: All authors have declared no conflicts of interest.

Keywords: Overall Survival, quality of life, financial toxicity, financial burden