Economic Evaluation of a Tumour-Agnostic Therapy: Dutch Economic Value of Larotrectinib in TRK Fusion-Positive Cancers.

BACKGROUND: Larotrectinib is the first tumour-agnostic therapy that has been approved by the European Medicines Agency. Tumour-agnostic therapies are indicated for a multitude of tumour types. The economic models supporting reimbursement submissions of tumour-agnostic therapies are complex because of the multitude of indications per model. OBJECTIVE: The objective of this paper was to evaluate the cost effectiveness of larotrectinib compared with standard of care in patients with cancer with tropomyosin receptor kinase fusion-positive tumour types in the Netherlands. METHODS: A previously constructed cost-effectiveness model with a partitioned survival approach was adapted to the Dutch setting, simulating costs and effects of treatment in patients with tropomyosin receptor kinase fusion-positive cancer. The cost-effectiveness model conducts a naïve comparison of larotrectinib to a weighted comparator standard-of-care arm. Dutch specific resource use and costs were implemented and inflated to reflect 2019 euros. The analysis includes a lifetime horizon and a societal perspective. RESULTS: Larotrectinib versus Dutch standard of care resulted in 5.61 incremental (QALYs) and €232,260 incremental costs, leading to an incremental cost-effectivenes ratio of €41,424/QALY. The probabilistic sensitivity analysis reveals a 88% chance of larotrectinib being cost effective compared with the pooled comparator standard-of-care arm at the applicable €80,000/QALY willingness-to-pay threshold in the Netherlands. CONCLUSIONS: The incremental cost-effectivenes ratio was well below the applicable threshold for diseases with a high burden of disease in the Netherlands (€80,000). At this threshold, larotrectinib was estimated to be a cost-effective treatment for patients with tropomyosin receptor kinase fusion-positive cancer compared with current standard of care in the Netherlands.

Healthcare Costs of Metastatic Cutaneous Melanoma in the Era of Immunotherapeutic and Targeted Drugs.

Immunotherapeutic and targeted drugs improved survival of patients with metastatic melanoma. There is, however, a lack of evidence regarding their healthcare costs in clinical practice. The aim of our study was to provide insight into real-world healthcare costs of patients with metastatic cutaneous melanoma. Data were obtained from the Dutch Melanoma Treatment Registry for patients who were registered between July 2012 and December 2018. Mean total/monthly costs per patient were reported for all patients, patients who did not receive systemic therapy, and patients who received systemic therapy. Furthermore, mean episode/monthly costs per line of therapy and drug were reported for patients who received systemic therapy. Mean total/monthly costs were € 89,240/€ 6809: € 7988/€ 2483 for patients who did not receive systemic therapy (n = 784) and € 105,078/€ 7652 for patients who received systemic therapy (n = 4022). Mean episode/monthly costs were the highest for nivolumab plus ipilimumab (€ 79,675/€ 16,976), ipilimumab monotherapy (€ 79,110/€ 17,252), and dabrafenib plus trametinib (€ 77,053/€ 12,015). Dacarbazine yielded the lowest mean episode/monthly costs (€ 6564/€ 2027). Our study showed that immunotherapeutic and targeted drugs had a large impact on real-world healthcare costs. As new drugs continue entering the treatment landscape for (metastatic) melanoma, it remains crucial to monitor whether the benefits of these drugs outweigh their costs.

Real-world healthcare costs of ipilimumab in patients with advanced cutaneous melanoma in The Netherlands.

There is limited evidence on the costs associated with ipilimumab. We investigated healthcare costs of all Dutch patients with advanced cutaneous melanoma who were treated with ipilimumab. Data were retrieved from the nation-wide Dutch Melanoma Treatment Registry. Costs were determined by applying unit costs to individual patient resource use. A total of 807 patients who were diagnosed between July 2012 and July 2015 received ipilimumab in Dutch practice. The mean (median) episode duration was 6.27 (4.61) months (computed from the start of ipilimumab until the start of a next treatment, death, or the last date of follow-up). The average total healthcare costs amounted to &OV0556;81 484, but varied widely (range: &OV0556;18 131-&OV0556;160 002). Ipilimumab was by far the most important cost driver (&OV0556;73 739). Other costs were related to hospital admissions (&OV0556;3323), hospital visits (&OV0556;1791), diagnostics and imaging (&OV0556;1505), radiotherapy (&OV0556;828), and surgery (&OV0556;297). Monthly costs for resource use other than ipilimumab were &OV0556;1997 (SD: &OV0556;2629). Treatment-naive patients (n=344) had higher total costs compared with previously-treated patients (n=463; &OV0556;85 081 vs. &OV0556;78 811). Although patients with colitis (n=106) had higher costs for resource use other than ipilimumab (&OV0556;11 426) compared with patients with other types of immune-related adverse events (n=90; &OV0556;9850) and patients with no immune-related adverse event (n=611; &OV0556;6796), they had lower total costs (&OV0556;76 075 vs. &OV0556;87 882 and &OV0556;81 480, respectively). In conclusion, this nation-wide study provides valuable insights into the healthcare costs of advanced cutaneous melanoma patients who were treated with ipilimumab in clinical practice. Most of the costs were attributable to ipilimumab, but the costs and its distribution varied considerably across subgroups.

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

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.

Time trends in chemotherapy (administration and costs) and relative survival in stage III colon cancer patients - a large population-based study from 1990 to 2008.

BACKGROUND: Use of adjuvant chemotherapy for stage III colon cancer has increased since several trials have shown the beneficial effect on survival. In this population-based study we show time trends in the administration and costs of chemotherapy and relative survival of patients with stage III colon cancer. METHODS: All patients surgically treated for adenocarcinoma of the colon stage III between 1990 and 2008 in The Netherlands were included. Relative survival (using period analyses) and Relative Excess Risks of death (RER) were calculated. The costs of chemotherapy were estimated. RESULTS: A total of 24 111 colon cancer patients with stage III were included in the cohort. The administration (from 9.5% in 1990 to 61.8% in 2008; p < 0.001) and costs of chemotherapy (from €38 467 in 1990 to €3 876 150 in 2008) increased during the study period. Multivariable relative survival improved for patients receiving adjuvant chemotherapy (RER 0.93; 95% CI 0.92-0.94; p < 0.001). In contrast, relative survival remained stable for patients, younger than 80 years, who did not receive chemotherapy (RER 1.00; 95% CI 1.00-1.01; p = 0.3). Patients aged 80 years and older without chemotherapy, relative survival increased during the study period (RER 0.98; 95% CI 0.97-0.99; p < 0.001). CONCLUSIONS: The administration, the costs of chemotherapy and the survival of patients with stage III colon cancer increased over time. Whereas the costs and administration of chemotherapy increased extensively, relative survival increased to a lesser extent. For patients treated with adjuvant chemotherapy relative survival increased equally in all age groups.