Thousands of melanoma patients in Europe have no access to new life saving drugs

Unacceptable inequalities in the availability and accessibility of new and effective cancer medications across Europe.

Over 5000 patients with metastatic melanoma in Europe are denied access to new, life-saving drugs every year, according to a survey presented at the ESMO 2016 Congress in Copenhagen. Metastatic melanoma is an aggressive and deadly skin cancer. With innovative targeted therapy and immunotherapy, patients can survive for many years. Unfortunately, new therapies are expensive so, according to a survey conducted by Dr Lidija Kandolf-Sekulovic, over 5000 patients with metastatic melanoma in Europe have no access to these drugs.

Before 2011 there were no effective treatment options for metastatic melanoma patients, but that has changed tremendously in the last 5 years. We now have medicines which can prolong overall survival of these patients to more than 18 months and, in some patients, durable responses lasting up to 10 years have been reported. However, access to these medicines is limited and patients and physicians are facing increasing difficulties to obtain them. This is especially the case for Eastern and South Eastern European countries, where a majority of patients are still treated with palliative chemotherapy that does not prolong overall survival,” said Kandolf-Sekulovic.

The survey showed that in Western Europe 70% of patients were treated with innovative medicines, while in Eastern Europe less than 10% of patients had access to the latest treatment recommended by current European Guidelines (ESMO, EORTC/EADO).

The study found that the BRAFi+MEKi combination (one of the first-line treatments besides immunotherapy for BRAF mutated metastatic melanoma) was registered in 75% of Western European countries and fully reimbursed in 58%. In Eastern Europe, the treatment was registered in 42% of countries and only reimbursed in 18%, with time-consuming administrative work needed to obtain the medicines in all cases.

The survey estimated that around 19.250 metastatic melanoma patients are treated every year in Europe and nearly 7.450 (39.7%) in Eastern and South-Eastern Europe. Of these patients, 5.128 (69%) do not have the access to first-line therapy according to European guidelines. Overall, it can be estimated that in Europe 5.228/19.250 (27%), i.e. almost one third of all metastatic melanoma patients, do not have access to innovative medicines.

In Europe, about 1 in every 100 people will develop melanoma at some point in their life, but important variations exist from one country to another. This number is increasing in almost all European countries. Melanoma is slightly more frequent in females than in males and more frequent in Switzerland, the Netherlands and the Scandinavian countries (Norway, Sweden and Denmark), where about 20 out of 100,000 people are diagnosed each year. From 1999-2012 there has been a 78% recorded increase in Germany. Similar increases were recorded also in the United States, Australia, Norway and Denmark, as well as countries in South-Eastern Europe.

Kandolf-Sekulovic explained: “Our study raises ethical questions on the inequalities that affect survival based on the country of residence in Europe. It is not new that disparities in healthcare can lead to disparities in overall survival of patients, but these disparities are becoming even sharper for patients with chemotherapy resistant metastatic melanoma in whom durable responses lasting for years can be seen in up to 20% of patients if treated with innovative medicines. In European healthcare systems that declare universal access to healthcare, these inequalities must be overcome.”

Dr Alexander Eniu, Chair of the ESMO Global Policy Committee, said: “This study confirms what ESMO has highlighted in the past: access to the best treatment according to evidence-based clinical guidelines such as ESMO’s, is not equal across Europe. ESMO advocates for equal access to treatment and care, which is the fundamental right of any patient. Despite the encouraging rate of new medicine development, there are still unacceptable inequalities in the availability and accessibility of new and effective cancer medications across Europe.”

The present study focuses on melanoma but the ESMO-led European Consortium Study on the availability and accessibility of anti-neoplastic medicines across Europe found that the same was true for other types of cancer, especially rare cancers, in countries with lower economic levels. It is important to continue to provide health authorities with data, and to carry on calling attention to the difficulties patients with incurable diseases are facing, in the hope that equal access will soon be a reality, at least in Europe,” said Eniu.

This everyday situation which is a source of a large frustration for metastatic melanoma patients, their families and physicians, needs to be addressed urgently by all stakeholders. We need harmonisation of reimbursement procedures throughout Europe, adjusted programmes for early access to innovative medicines in countries with delayed reimbursement and sustainable pricing for these life-saving drugs,” concluded Kandolf-Sekulovic.

European Society for Medical Oncology Congress 2016 Copenhagen, Denmark

Advertisements

Cancer treatment as a double-edged sword

Even with today’s safer and more targeted anti-cancer drugs, scientists have been unable to satisfactorily explain the phenomenon of why treated cancers so often recur. The common theory is that the cancer cell develops “internal resistance to treatment,” and overrides the toxic effects of the drug.
Now, findings by a team of scientists led by Professor Yuval Shaked of the Technion-Israel Institute of Technology Faculty of Medicine and the Technion Integrated Cancer Center (TICC) could provide the key for reducing recurrence, and allowing anti-cancer drugs to do work as intended.

In their study published in The Journal of Pathology, the team shows that tumor relapse occurs when the body, in effect, mobilizes itself in favor of the tumor, causing recurrence of the disease, increasing its aggressiveness and creating metastases or tumor spread. Even selective, highly focused treatments that harm cancer cells almost exclusively lead to a similar response.

The administration of an anti-cancer drug is very aggressive intervention in the body,” explains Prof. Shaked. “Therefore, the body responds to chemotherapy the way it responds to trauma. This creates the effect of a double-edged sword: although chemotherapy kills cancer cells, it also causes the secretion of substances that confer resistance to the tumor. Even more selective treatments, with fewer side effects, cause physiological reactions that increase the aggressiveness of the disease.”

In this specific study, among other studies the group has published in this area, mice with multiple myeloma — a malignant disease of the plasma cells produced in bone marrow and spread throughout the body via the circulatory system — were treated with the selective anti-cancer drug Velcade (bortezomib). (Velcade is based on the discovery of ubiquitin, for which Professors Avram Hershko and Aaron Ciechanover of the Technion Faculty of Medicine won the Nobel Prize.)

The researchers found that treatment with Velcade led to a physiological reaction that actually reinforced the intensity of the myeloma in the mice. According to Prof. Shaked, the drug caused inflammatory cells (macrophages) in the bone marrow to enhance the aggressiveness of the disease and provide the cancer cells with resistance to treatment.

It is important to clarify that treatment with Velcade is essential and necessary,” says Prof. Shaked, “but its disadvantage is that along with the benefit there is damage.”

Next steps: inhibiting the mechanism that enhances the tumor

According to Prof. Shaked, “…understanding the mechanisms that enhance the tumor and accelerate the spread of metastases will enable us to develop methods to inhibit them.”

In fact, when the researchers inhibited the secreted factor related to the activity of inflammatory cells, they observed a decrease in the proliferation of cancer cells. Now they are working on various ways to inhibit the body’s response to anti-cancer treatments.

Ultimately we are talking about a trade-off between the intensity of the treatment and the intensity of the physical response. The moment the ratio is in favor of the treatment and to the detriment of the response, we will achieve effective treatment without a ‘fine’ in the form of enhanced metastasis. In addition, we can inhibit the body’s response using existing drugs, thereby enabling the anticancer drugs to get the job done.

Beyar-Katz, et al. Bortezomib-induced pro-inflammatory macrophages as a potential factor limiting anti-tumour efficacy. The Journal of Pathology, 2016; 239 (3): 262 DOI: 10.1002/path.4723 [Abstract]