Some Europeans with melanoma lack access to new, lifesaving drugs

Costly therapies more available to patients in Western than in Southern, Eastern Europe

Despite the existence of new, lifesaving drugs to treat patients with metastatic melanoma, more than 5000 patients in Europe are being denied access to them, according to a survey presented at the European Society for Medical Oncology (ESMO) 2016 Congress, held October 7 to 11 in Copenhagen, Denmark.

New therapies that first became available in 2011 have dramatically changed the treatment of the disease, prolonging the overall survival of these patients to more than 18 months and, in some cases, 10 years and longer.

Nevertheless, because the therapies are so expensive, patients and physicians are having difficulty accessing them, particularly in Eastern and Southern Europe, where the majority of patients still are treated with palliative chemotherapy that does not prolong overall survival, according to Lidija Kandolf- Sekulović, MD, PhD, of the Military Medical Academy in Belgrade, Serbia, who led the research.

In Western Europe, for example, approximately 70% of patients were treated with innovative medicines, whereas in Eastern Europe, fewer than 10% of patients had access to the latest treatments recommended by current European guidelines (ESMO and the European Organisation for Research and Treatment of Cancer/European Association of Dermato-Oncology), the survey found.

The combination of BRAF and MEK inhibition (one of the first-line treatments aside from immunotherapy for patients with BRAF-mutated metastatic melanoma) was registered in approximately 75% of Western European countries and fully reimbursed in 58%, according to the survey. Meanwhile, the treatment was registered in approximately 42% of Eastern European countries and reimbursed in only 18%.

“The main reasons for the disparities are different socioeconomic factors, including the high price of innovative medicines, low gross national income, and health expenditures per capita,” Dr. Kandolf-Sekulović says. “Health care system inefficiency—the inability to adapt to the increasing number of innovative medicines and the rising price of treatment—plays a role as well,” she adds.

Stronger Disparities in Recent Years

According to survey estimates, nearly 19,250 patients with metastatic melanoma are treated every year in Europe, with nearly 7450 cases (39%) occurring in Eastern and Southeastern Europe. Of the latter group, 5128 patients (69%) do not have access to first-line therapies as defined by European guidelines. Among all European patients with metastatic melanoma, this rate is much lower: Only one-third do not have access to these new therapies.

“It is not new that disparities in health care can lead to disparities in overall survival of patients, but these disparities are becoming even sharper for patients with chemotherapyresistant metastatic melanoma in whom durable responses lasting for years can be seen in up to 20% of patients if treated with innovative medicines,” Dr. Kandolf-Sekulović notes in an ESMO-issued press release. “In European health care systems that declare universal access to health care, these disparities must be overcome.”

Dr. Hussein Tawbi, MD, PhD, associate professor in the department of melanoma medical oncology at the University of Texas MD Anderson Cancer Center in Houston, agrees. His research focuses on early-phase treatments for melanoma and sarcoma, and he helped to develop some of the new melanoma treatments in his previous faculty position at the University of Pittsburgh.

“I'm very interested in bringing these drugs to new populations, including patients with brain metastases and others who have been excluded from clinical trials because of immune diseases, so the concept of disparity has been on my mind for a while,” Dr. Tawbi says. He calls it “absolutely sad and disheartening to see that patients in Europe have to be treated with 2003 medicines as opposed to 2016 medicines.”

Dr. Tawbi elaborates on the dramatic transformation in the treatment of metastatic melanoma over the past 5 to 6 years: “Before, we started every conversation with these patients saying that their expected survival was 6 to 9 months and that there had been no improvements in survival in the last 30 years,” he says. “We seldom used the word ‘cure’ except in very select patients with high-dose interleukin-2, which was restricted to specific medical centers and had about 5% cure rates.”

However, in 2011, the US Food and Drug Administration (FDA) began approving medicines that have significantly increased overall survival for patients with the disease. For example, ipilimumab, a monoclonal antibody that works to activate the immune system by targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4), doubled 1-year survival rates and ultimately led to approximately 22% of patients achieving long-term survival of 10 years. “It was an absolute transformation; within 48 hours, almost 90% of patients will have some tumor shrinkage that could last almost a year,” he says.

Nevertheless, patients experienced severe toxicities from the drug. Programmed cell death protein 1 (PD-1) antibodies followed, tripling response rates to approximately 45% and reducing toxicity by approximately one-third, Dr. Tawbi says. At the same time, BRAF inhibitors also significantly improved treatment for patients with metastatic melanoma who carried this genetic mutation. And combination therapies, which were approved by the FDA in 2014, are proving even more promising. “Now I can say we're currently able to cure almost half of our metastatic melanoma patients, and our population is usually younger, so the disease has the biggest impact on productive life-years lost,” Dr. Tawbi says.

Cost and Approval Barriers

Many patients in Europe are not seeing these benefits. “The cost of these drugs is so significant that even places with access to them may not be able to afford it,” he says.

Dr. Tawbi cites an example of a resident physician from Estonia who was visiting The University of Texas MD Anderson Cancer Center and was learning about using these new treatments while at the same time commenting that he will not be able to treat his own patients with them. Instead, he must treat them with a type of chemotherapy that was approved by the FDA in the 1970s and results in a median survival of 6 weeks.

Another reason why these drugs are not available as quickly in Europe is the different approval processes, says Michael Atkins, MD, deputy director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.

The FDA and Centers for Medicare and Medicaid Services do not consider cost-effectiveness in their decision to approve a medication, whereas that is an important concern for many European countries, Dr. Atkins says. He adds that some of those countries have a central budget for health care expenditures per year and, consequently, they need to prioritize. “Usually, the therapies will eventually get approved, but it's a tragedy when you have drugs shown to produce a significant survival advantage yet patients don't have access,” he says.

The main reasons for the disparities are different socioeconomic factors, including the high price of innovative medicines, low gross national income, and health expenditures per capita. Health care system inefficiency … plays a role as well. —Lidija Kandolf-Sekulović, MD, PhD

Nevertheless, he is optimistic that the disparities will improve, noting that if researchers conduct the survey within the next few years, disparities may then be either much smaller or nonexistent.

Alexandru Eniu, MD, PhD, chair of the ESMO global policy committee, says disparities also exist in treatments for other cancers, especially rare cancers, in countries with lower economic levels. He stresses the importance of continuing to provide health authorities with data and calling attention to the difficulties experienced by patients with incurable diseases.

Dr. Kandolf-Sekulović says that harmonizing pricing and reimbursement processes is difficult to achieve among different national health care systems in Europe; however, she sees hope for prioritizing lists of innovative medicines for reimbursement on a broad European level in the next few years. The European Technology Assessment Group is working to harmonize pricing within the European Union (EU) by 2019, whereas ESMO is developing magnitude-of-benefit scales that will aid in assessing the true clinical benefit of every new health technology, including drugs, she says.

Among other high priorities are the development of more sustainable pricing as well as programs for early access to innovative medicines in countries with delayed reimbursement, she notes. Meanwhile, Dr. Kandolf-Sekulović and others will continue to work to call attention to the problem.

“Through dialogue with other oncological organizations, the World Health Organization Expert Committee on the Selection and Use of Essential Medicines, patient advocacy organizations, EU and national policy makers, and pharmaceutical industry representatives, these disparities could be ameliorated in the future,” she says.