Elsevier

European Journal of Cancer

Volume 72, February 2017, Pages 156-165
European Journal of Cancer

Original Research
Dutch Melanoma Treatment Registry: Quality assurance in the care of patients with metastatic melanoma in the Netherlands

https://doi.org/10.1016/j.ejca.2016.11.021Get rights and content

Highlights

  • This is the first multipurpose nationwide registry for metastatic melanoma.

  • Collaboration of all stakeholders from the start has been the key to its success.

  • Toxicity rates of the new drugs were consistent with the results of the pivotal trials.

  • Median overall survival was 10.1 and 12.7 months in the first 2 registration years.

  • The DMTR can be used as a blueprint for future real-world data initiatives.

Abstract

Background

In recent years, the treatment of metastatic melanoma has changed dramatically due to the development of immune checkpoint and mitogen-activated protein (MAP) kinase inhibitors. A population-based registry, the Dutch Melanoma Treatment Registry (DMTR), was set up in July 2013 to assure the safety and quality of melanoma care in the Netherlands. This article describes the design and objectives of the DMTR and presents some results of the first 2 years of registration.

Methods

The DMTR documents detailed information on all Dutch patients with unresectable stage IIIc or IV melanoma. This includes tumour and patient characteristics, treatment patterns, clinical outcomes, quality of life, healthcare utilisation, informal care and productivity losses. These data are used for clinical auditing, increasing the transparency of melanoma care, providing insights into real-world cost-effectiveness and creating a platform for research.

Results

Within 1 year, all melanoma centres were participating in the DMTR. The quality performance indicators demonstrated that the BRAF inhibitors and ipilimumab have been safely introduced in the Netherlands with toxicity rates that were consistent with the phase III trials conducted. The median overall survival of patients treated with systemic therapy was 10.1 months (95% confidence interval [CI] 9.1–11.1) in the first registration year and 12.7 months (95% CI 11.6–13.7) in the second year.

Conclusion

The DMTR is the first comprehensive multipurpose nationwide registry and its collaboration with all stakeholders involved in melanoma care reflects an integrative view of cancer management. In future, the DMTR will provide insights into challenging questions regarding the definition of possible subsets of patients who benefit most from the new drugs.

Introduction

Malignant melanoma is one of the most aggressive types of skin cancer. The incidence of melanoma has increased in Europe over the past few decades [1], [2]. In the Netherlands, the number of new cases of invasive melanoma (all stages) more than doubled between 2000 and 2014 and it accounts for approximately 90% of skin-cancer-related mortality in 2014 [3]. The increased incidence accompanied by the high mortality rates made it one of the worst-performing tumours in the Netherlands over recent years, especially for males [4].

The treatment of unresectable and metastatic melanoma has changed dramatically in recent years due to the development of immune checkpoint inhibitors (e.g. ipilimumab, nivolumab and pembrolizumab) and inhibitors of the mitogen-activated protein (MAP) kinase pathway (e.g. the BRAF inhibitors vemurafenib and dabrafenib and the MAP kinase kinase (MEK) inhibitors trametinib and cobimetinib) [5], [6], [7], [8]. These drugs create new opportunities to prolong progression-free and overall survival (OS) for patients with metastatic melanoma. However, the introduction of the new drugs poses several challenges. First, adequate selection of subsets of patients who may benefit from immune checkpoint inhibitors or MAP kinase inhibitors and sequencing these new drugs present a challenge. Second, experience in recognising and treating the potentially life-threatening side-effects of immune checkpoint inhibitors is essential. Finally, the high costs of these new drugs raise questions about their cost-effectiveness in daily clinical practice.

The introduction of the new drugs to treat metastatic melanoma was approved by the Dutch Minister of Health subject to two firm conditions: I) the concentration of metastatic melanoma treatment in a limited number of designated centres and II) the recording of all patients with unresectable or metastatic melanoma (stage IIIc or stage IV melanoma) in a nationwide registry.

To achieve centralisation, the Dutch Society of Medical Oncologists (NVMO) selected 14 hospitals as melanoma centres in 2012. These centres were chosen on the basis of their expertise in the systemic treatment of melanoma, their infrastructure and their geographic distribution. At the same time, a set of multidisciplinary quality standards was established by the professional organisations involved in melanoma treatment, including a minimum volume standard of 20 new patients annually receiving systemic treatment for metastatic melanoma [9]. This number of patients is based on safety reports in clinical trials [5], [6]. In addition, it was assumed that this would allow the centres to have sufficient experience in treating patients with severe toxicity.

The Dutch Melanoma Treatment Registry (DMTR) was set up in July 2013. A unique consortium of organisations, including medical specialists, policymakers, healthcare researchers, patient advocates and pharmaceutical companies, was involved in establishing the registry.

This article describes the design and the objectives of the DMTR and presents some results of the first 2 years of registration.

Section snippets

Objectives of the DMTR

The DMTR was designed to serve multiple objectives: I) clinical auditing, II) improving transparency concerning the quality of melanoma care, III) providing an insight into real-world outcomes on effects and costs and IV) to create a platform for research.

Patient characteristics

From 1st July 2012 to 1st July 2014, 1472 patients with metastatic melanoma were registered in the DMTR. A total of 60 patients were not referred to a melanoma centre and therefore received only a concise entry mainly due to poor performance status or limited prognosis. Of all the patients referred to a melanoma centre (n = 1412), 23 patients (1.6%) were excluded because of missing data on date of birth, date of first visit to a melanoma centre, date of diagnosis of disseminated disease and the

Discussion

This article reports on the start-up and key elements of the DMTR. The DMTR is unique in its collaboration between all stakeholders involved in treating metastatic melanoma, and its multipurpose design. The active participation of the 14 dedicated melanoma centres led to the nationwide coverage of all patients with metastatic melanoma in the registry within the first year.

The results of the DMTR demonstrate that treatment with BRAF inhibitors and ipilimumab has been implemented as standard of

Funding

This work was supported by the Netherlands Organisation for Health Research and Development (ZonMW) [grant no. 836002002]. The Dutch Melanoma Treatment Registry (DMTR) was sponsored by Roche Nederland B.V, Bristol-Myers Squibb (BMS), GlaxoSmithKline (GSK)/Novartis and Merck Sharp & Dohme (MSD).

Role of the funding source: representatives of the pharmaceutical companies that sponsor the DMTR and ZonMW have a seat on the advisory board. This body advises the Board of Directors and the Medical

Conflict of interest statement

None declared.

Acknowledgments

The authors thank all physicians and data managers who registered the data in the Dutch Melanoma Treatment Registry. They would also like to thank ZonMW and the pharmaceutical companies for their financial support.

References (27)

  • Cijfersoverkanker. Available from: http://www.cijfersoverkanker.nl/ [Accessed 18 June...
  • H.E. Karim-kos et al.

    Progress against cancer in the Netherlands since the late 1980s : an epidemiological evaluation

    Intern J Cancer

    (2012)
  • F.S. Hodi et al.

    Improved survival with ipilimumab in patients with metastatic melanoma

    N Engl J Med

    (2010)
  • Cited by (0)

    1

    Both authors contributed equally.

    View full text