Estimating healthcare resource use associated with the treatment of metastatic melanoma in eight countries

Objectives Studies reporting healthcare resourse use (HRU) for melanoma, one of the most costly cancers to treat, are limited. Using consistent, robust methodology, this study estimated HRU associated with the treatment of metastatic melanoma in eight countries.

Methods Using published literature and clinician input, treatment phases were identified: active systemic treatment (pre-progression); disease progression; best supportive care (BSC)/palliative care; and terminal care. HRU elements were identified for each phase and estimates of the magnitude and frequency of use in clinical practice were obtained through country-specific Delphi panels, comprising healthcare professionals with experience in oncology (n?=?8).

Results Medical oncologists are the key care providers for patients with metastatic melanoma, although in Germany dermato-oncologists also lead care. During the active systemic treatment phase, each patient was estimated to require 0.83–2 consultations with a medical oncologist/month across countries; the median number of such assessments in 3 months was highest in Canada (range?=?3.5–5) and lowest in France, the Netherlands and Spain (1). Resource use during the disease progression phase was intensive and similar across countries: all patients were estimated to consult with medical oncologists and 10–40% with a radiation oncologist; up to 40% were estimated to require a brain MRI scan. During the BSC/palliative care phase, all patients were estimated to consult with medical oncologists, and most to consult with a primary care physician (40–100%).

Limitations Panelists were from centers of excellence, thus results may not reflect care within smaller hospitals; data obtained from experts may be less variable than data from broader clinical practice. Treatments for metastatic melanoma are continually emerging, thus some elements of our work could be superseded.

Conclusions HRU estimates were substantial and varied across countries for some resources. These data could be used with country-specific costs to elucidate costs for the management of metastatic melanoma.     

Confirming the timing of phase-based costing in oncology studies: a case example in advanced melanoma

Aims: The utilization of healthcare services and costs among patients with cancer is often estimated by the phase of care: initial, interim, or terminal. Although their durations are often set arbitrarily, we sought to establish data-driven phases of care using joinpoint regression in an advanced melanoma population as a case example.

Methods: A retrospective claims database study was conducted to assess the costs of advanced melanoma from distant metastasis diagnosis to death during January 2010–September 2014. Joinpoint regression analysis was applied to identify the best-fitting points, where statistically significant changes in the trend of average monthly costs occurred. To identify the initial phase, average monthly costs were modeled from metastasis diagnosis to death; and were modeled backward from death to metastasis diagnosis for the terminal phase. Points of monthly cost trend inflection denoted ending and starting points. The months between represented the interim phase.

Results: A total of 1,671 patients with advanced melanoma who died met the eligibility criteria. Initial phase was identified as the 5-month period starting with diagnosis of metastasis, after which there was a sharp, significant decline in monthly cost trend (monthly percent change [MPC]?=?–13.0%; 95% CI?=?–16.9% to –8.8%). Terminal phase was defined as the 5-month period before death (MPC?=?–14.0%; 95% CI?=?–17.6% to –10.2%).

Limitations: The claims-based algorithm may under-estimate patients due to misclassifications, and may over-estimate terminal phase costs because hospital and emergency visits were used as a death proxy. Also, recently approved therapies were not included, which may under-estimate advanced melanoma costs.

Conclusions: In this advanced melanoma population, optimal duration of the initial and terminal phases of care was 5 months immediately after diagnosis of metastasis and before death, respectively. Joinpoint regression can be used to provide data-supported phase of cancer care durations, but should be combined with clinical judgement.     

Years of life lost due to metastatic melanoma in 12 countries

Background:

Regionally or distantly metastatic melanoma (stages IIIB/C and IV) place a high burden on society. To quantify this burden, this study estimated years of life lost (YLL) per patient for adults with metastatic melanoma in 12 countries in 2014.

Methods:

General population growth and life expectancy were estimated from the Organization for Economic Co-operation and Development data and life tables for each country. Incidence of melanoma and mortality rates for the disease were based on GLOBOCAN and US registry data. The prevalence of metastatic melanoma was calculated using mortality rates and survival data from patients with melanoma. YLL per patient was estimated by the difference between the disease-free life expectancy and the life expectancy with metastatic melanoma.

Results:

YLL per patient were as follows: Australia, men?=?19.9 years, women?=?22.7 years; Brazil, 16.3, 19.8; Canada, 19.4, 22.3; France, 18.8, 23.1; Germany, 18.3, 20.8; Italy, 19.3, 22.7; Mexico, 17.2, 19.0; the Netherlands, 18.5, 21.5; Spain, 19.2, 23.1; Sweden 19.4, 22.0; the UK, 18.7, 21.2; and the US, 17.9, 20.6.

Conclusions:

The burden of metastatic melanoma as measured by YLL is substantial in all 12 countries; although there is variation across countries and between men and women.     

Cost and economic burden of adverse events associated with metastatic melanoma treatments in five countries

Objective: To estimate per-event cost and economic burden associated with managing the most common and/or severe metastatic melanoma (MM) treatment-related adverse events (AEs) in Australia, France, Germany, Italy, and the UK.

Methods: AEs associated with chemotherapy (dacarbazine, paclitaxel, fotemustine), immunotherapy (ipilimumab), and targeted therapy (vemurafenib) were identified by literature review. Medical resource use data associated with managing AEs were collected through two blinded Delphi panel cycles in each of the five countries. Published costs were used to estimate per-event costs and combined with AEs incidence, treatment usage, and MM prevalence to estimate the economic burden for each country.

Results: The costliest AEs were grade 3/4 events due to immunotherapy (Australia/France: colitis; UK: diarrhea) and chemotherapy (Germany/Italy: neutropenia/leukopenia). Treatment of AEs specific to chemotherapy (Australia/Germany/Italy/France: neutropenia/leukopenia) and targeted therapy (UK: squamous cell carcinoma) contributed heavily to country-specific economic burden.

Limitations: Economic burden was estimated assuming that each patient experienced an AE only once. In addition, the context of settings was heterogeneous and the number of Delphi panel experts was limited.

Conclusions: Management costs for MM treatment-associated AEs can be substantial. Results could be incorporated in economic models that support reimbursement dossiers. With the availability of newer treatments, establishment of a baseline measure of the economic burden of AEs will be crucial for assessing their impact on patients and regional healthcare systems.     

Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States

Abstract

Aims: To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US health system perspective.

Materials and methods: A Markov cohort model with four health states (recurrence-free, locoregional recurrence, distant metastases, and death) was developed to estimate costs, life-years, and quality-adjusted life-years (QALYs) associated with pembrolizumab vs observation over a lifetime (46-year) horizon. Using a parametric multi-state modeling approach, transition probabilities starting from recurrence-free were estimated based on patient-level data from KEYNOTE-054 (NCT02362594), a direct head-to-head phase 3 trial. Post-recurrence transition probabilities were informed by real-world retrospective data and clinical trials in advanced melanoma. Health state utilities and adverse event-related disutility were derived from KEYNOTE-054 trial data and published literature. Costs of drug acquisition and administration, adverse events, disease management, and terminal care were estimated in 2018?US dollars. Deterministic and probabilistic sensitivity analyses were conducted to assess robustness.

Results: Over a lifetime horizon, adjuvant pembrolizumab and observation were associated with total QALYs of 9.24 and 5.95, total life-years of 10.54 and 7.15, and total costs of $489,820 and $440,431, respectively. The resulting incremental cost-effectiveness ratios (ICERs) for pembrolizumab vs observation were $15,009/QALY and $14,550/life-year. Across the range of input values and assumptions tested in deterministic sensitivity analyses, pembrolizumab ranged from being a dominant strategy to having an ICER of $57,449/QALY vs observation. The ICER was below a willingness-to-pay threshold of $100,000/QALY in 90.2% of probabilistic simulations.

Limitations: Long-term extrapolation of outcomes was based on interim results from KEYNOTE-054, with a median follow-up of 15?months.

Conclusions: Based on common willingness-to-pay benchmarks, pembrolizumab is highly cost-effective compared with observation alone for the adjuvant treatment of completely resected stage III melanoma in the US.