Pembrolizumab Found to Be Cost-Effective in Advanced Melanoma Interview with:

Herbert H F Loong MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine) Specialist in Medical Oncology Clinical Assistant Professor, Department of Clinical Oncology Deputy Medical Director, Phase 1 Clinical Trials Centre The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong SAR

Dr. Herbert Loong

Herbert H F Loong
Specialist in Medical Oncology
Clinical Assistant Professor, Department of Clinical Oncology
Deputy Medical Director, Phase 1 Clinical Trials Centre
The Chinese University of Hong Kong
Prince of Wales Hospital
Hong Kong SAR What is the background for this study? 

Response: Advanced melanoma have previously been known to be a disease with a dismal prognosis. Over the last few years, clinical trials data and real-world clinical experience of checkpoint inhibitors have significantly changed the treatment landscape for advanced melanoma patients. This was first demonstrated with the Anti-CTLA4 Ab Ipilimumab, and more recently with the Anti-PD1 Ab pembrolizumab. Whilst we have seen dramatic improvements in disease control with the use of these agents, the high costs of these drugs may be prohibitive to the average patient who has to pay out-of-pocket and potentially may place significant burdens on healthcare systems. There is a need to rationally assess the cost-effectiveness of these new agents, specifically addressing the potential benefits to the individual patient and to society, whilst balancing the costs that such a treatment may entail.

The assessment of cost-effectiveness of a particular treatment is extremely important in Hong Kong, as this has direct implications on drug reimbursement and accessibility of the particular drug in question at public hospitals in Hong Kong. The aim of the study is to assess the cost-effectiveness of pembrolizumab in patients with advanced melanoma used in the first-line setting in Hong Kong, and comparing it to (1) ipilimumab and (2) cytotoxic chemotherapy. Cytotoxic chemotherapy chosen for comparison were drugs commonly used in the first line setting in Hong Kong, which included dacarbazine, temozolomide and carboplatin+paclitaxel combination. It is important to note that whilst ipilimumab is registered for this indication in Hong Kong, there is no reimbursement of this drug by the Hospital Authority in Hong Kong and patients have to pay out-of-pocket. The cost of ipilimumab and the associated side effects has been prohibitive to most advanced melanoma patients in the public setting. What are the main findings?

Response: This study was conducted after retrieval of the following information:

–         Efficacy of the various treatments were extrapolated from landmark clinical trials involving the various agents

–         The costs of the drugs (in the public setting) were obtained

–         The incidence of various adverse events of the different treatments were also obtained from their reported clinical trials

–         The cost of drug administration and management of adverse events were calculated based on what specific treatments/investigations/management a particular adverse event may entail in the eyes of a practicing oncologist. The itemized cost of each of these components were obtained from the HK Government Gazette and published information from the Hong Kong Hospital Authority.

Biostatical modelling was performed based on a 3-stage partitioned survival model. This means that we determined a fixed cost per unit time for patients at each of the following stages of their disease journey (1) Progression-free state, (2) disease progression state, (3) death.

We determined the (a) life-years gained, the (b) Quality Adjusted Life Years (QALYs), the (c) Total cost (which included drug administration cost, disease management cost, death related cost and adverse event cost) and the (d) incremental cost effectiveness ratio (ICER) between the comparative treatments. What should readers take away from this report?

Response: We found that, based on the World Health Organization’s (WHO) threshold of a new treatment being cost effective if the ICER is less than three times the national Gross Domestic Product (GDP) [HK 3xGDP = USD 119,274], pembrolizumab can be considered cost effective relative to both ipilimumab and also cytotoxic chemotherapy when used in the first line setting. The ICER of pembrolizumab vs. ipilimumab is USD 8034/QALY and pembrolizumab vs. cytotoxic chemotherapy (using dacarbazine as representation) is USD53,123/QALY.

This is the first study to address the issue of cost-effectiveness of checkpoint inhibitors in the management of advanced cancer in Hong Kong. Specifically, we have determined that whilst pembrolizumab is expensive, the increase in QALYs gained with this treatment when compared with either standard cytotoxic chemotherapy, and even more so with ipilimumab, qualifies it as a cost-effective approach. We hope that this information can be considered by the healthcare authorities in the territory to consider the inclusion of pembrolizumab as a reimbursable item in the first-line setting of advanced melanoma patients. This will help ensure patients’ access to an effective treatment. What recommendations do you have for future research as a result of this study?

Response: The modelling for this study was based on results from clinical trials which were not conducted in Hong Kong. The fact that they were based on a clinical trials, and not a clinical practice population, as well as from overseas, may result in some bias in the results. Its applicability to our local Hong Kong population may also be in question. However, as the experience of use of pembrolizumab either in clinical trials or in clinical practice in Hong Kong have been sparse, the current modelling method is possibly the best we have. Going forward, we will be conducting a single-arm phase II open-labelled trial of pembrolizumab in acral lentiginous melanoma in Hong Kong [ NCT02875132]. Hopefully we will be able to generate some cost, adverse events, and quality-of-life/utility data of our local population.


ESMO Asia 2016 abstract:

Cost-effectiveness of pembrolizumab compared to ipilimumab and chemotherapy as a first line treatment for patients with advanced melanoma in Hong Kong

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on December 23, 2016 by Marie Benz MD FAAD