With more than 200 million people, Brazil has the largest population of any South American country and is currently the seventh most populous country in the world. The Brazilian population's average age is increasing, meaning more residents are at higher risk of developing cancer, including hematologic malignancies.
But, historically, Brazil lagged behind other developed countries in terms of treating patients with certain hematologic malignancies. For example, by the late 1990s, in countries where patients diagnosed with acute promyelocytic leukemia (APL) were treated early with all-trans retinoic acid (ATRA)-based regimens, 85% achieved long-term disease-free survival. In Brazil in the 1990s, however, fewer than 60% of patients achieved this goal, even though ATRA was approved for use in the country.
Recognizing a clear opportunity for improvement, Brazilian hematologists and researchers teamed up with international leukemia experts and organizations like the American Society of Hematology (ASH) to launch the International Consortium on Acute Promyelocytic Leukemia (IC-APL) in 2004. The network's main initial objective was to develop strategies for more rapid diagnosis and more effective treatment of APL. While the program made substantial improvements in these areas, challenges still remain.
Health Care Disparities in Brazil: Public Vs. Private
Brazil has had a universal health care system since 1988, Sistema Ãšnico de SaÃºde (SUS), which provides the sole care for most of the population and under which free health care is a right for all citizens. Resources are limited, though, and the SUS often does not cover more expensive treatments for cancer.
Approximately one-quarter of the population can afford additional private insurance, and for these patients, new and innovative drugs are often available. But for most of the population whose only health care coverage comes from SUS, access to newer drugs is often restricted because of cost.
"We have an imbalance between the two systems," said Angelo Maiolino, MD, PhD, a hematologist who works with the Brazilian Association of Hematology, Hemotherapy, and Cellular Therapy (ABHH). "For those with private insurance, we have access to the more innovative oncology treatments and new drugs. Unfortunately, in the public health system, due to reimbursement, we cannot access these novel drugs. It's totally an unfair system, but it is our reality."
Other challenges include long travel times for some patients given the large size of Brazil and many sparsely populated rural areas, and limited space in the few specialized treatment facilities that are equipped to handle patients with blood cancers. ASH Clinical News spoke with Dr. Maiolino and hematologists Lorena Lobo de Figueiredo Pontes, MD, PhD, and Eduardo Rego, MD, PhD, about international efforts to increase access to quality treatment in Brazil.
Cancer Treatment in Brazil
The Brazilian population isn't just large, it's aging, which means more individuals are at risk of developing noncommunicable diseases like blood cancers.1 In the 1960s, only 4.1% of people living in Brazil were over the age of 60, but demographers predict that more than 15% of the population will be older than 60 by 2025. This has translated to a growing incidence of new cancers and more cancer-related mortality in the country: More than 550,000 new cases of cancer were identified in 2018, and almost 250,000 people died of cancer that same year.2
Even if patients do have health care insurance that covers a treatment for their disease, their ability to access it may depend on where they live. There are nearly 8,000 hospitals in Brazil, but the majority are relatively small – holding an average of about 24 beds – and hospitals are concentrated in the country's relatively wealthier Southern region. Few hospitals offer specialized care for patients with hematologic malignancies.3
A 2019 study identified 299 high-complexity oncology services in Brazilian facilities but also found that these facilities were concentrated in just 173 municipalities – representing 3.1% of the country's 5,570 municipalities. In some states, there were no authorized locations where patients could receive some types of cancer care such as radiotherapy, pediatric oncology, or hematologic oncology services.4
"People can go long periods – more than what we would like it to be – waiting for bone marrow transplants, for example," said Dr. Rego, Chair of ASH's International Members Committee, who treats patients at the University of SÃ£o Paulo. "This is because we have fewer beds than what would be necessary based on the population of more than 200 million that we have here in Brazil. The access [to transplants] is difficult, and even hematology centers are restricted."
Dr. Rego added that, due to the uneven distribution of hematology and oncology centers, patients with hematologic malignancies living in rural regions need to be transferred to specialized hospitals, which takes time – a major problem for conditions such as APL, where urgent diagnosis and initiation of therapy is needed to avoid early mortality.
Regulatory Approval and Drug Coverage
Any drug to be offered in Brazil needs to be approved by the country's regulatory authority, the National Sanitary Surveillance Agency, or ANVISA. In the past, the organization had a reputation for failing to quickly approve drugs that had already been shown effective in other countries. "Five to 10 years ago, we had problems with ANVISA rejecting drugs like lenalidomide for myeloma and myelodysplastic syndromes, for example," Dr. Maiolino said. "It was a big problem. But nowadays, ANVISA is doing a very good job."
However, once a drug is approved by ANVISA, the government is not required to incorporate it into its list of medications available through SUS, Dr. de Figueiredo Pontes pointed out. Another agency, CONITEC (National Commission for the Incorporation of Technologies), must evaluate the costs and benefits of a new treatment and make recommendations as to whether it should be covered for SUS beneficiaries. Often, even if a drug is effective, the SUS budget simply cannot afford to incorporate it.
To gain access to medications that are approved but not reimbursed, many citizens have taken to the court system, arguing for the right to health – which is guaranteed in the Brazilian Constitution – as an alternative pathway to accessing certain types of health care.5 So-called "right-to-health litigation" is now a common practice in the country, explained Dr. Maiolino.
"The impact of networking cannot be overstated. We have been able to move much faster than we would without the support."
â€”Eduardo Rego, MD, PhD
Often, these lawsuits are over access to oral medications that are typically not covered in public and private insurance programs, which are required to cover only anticancer drugs that are administered parenterally. That changed in 2013, when, after strong lobbying efforts from several nongovernmental organizations and a social media campaign that garnered more than 18,000 signatures, the Brazilian Congress approved legislation mandating that all private health insurance companies provide access to oral antineoplastic treatment.
Dr. Maiolino said, however, that he often needs to use different drugs to treat patients under each system based on costs. "For multiple myeloma, I can treat a patient in the private health system with first-line daratumumab, lenalidomide, and dexamethasone," he said, but that combination would be unavailable if the same patient had public health insurance. "For a patient without private insurance, I'd have to treat the patient with cyclophosphamide, thalidomide, and dexamethasone instead."
When the IC-APL was initially formed in 2004, APL was chosen as a model disease because of the high rate of cure if the diagnosis is made quickly and effective therapy started rapidly. Clinicians in the original IC-APL countries – Brazil, Mexico, Uruguay, and Chile – hoped that developing solutions to improve care for this relatively small but high-stakes patient population could lead to new strategies for tackling many other cancers with below-optimal outcomes in these countries.
To accomplish these goals, the IC-APL built a network of experts and facilities to collect data. Early in its existence, the IC-APL team realized that, in addition to having limited access to the most novel drugs, patients in Brazil were being diagnosed far later in the progression of their disease than their counterparts in more developed countries. To provide the most effective treatment, they realized, patients would need to be diagnosed sooner.
Unfortunately, many Brazilian patients with APL start out in busy emergency rooms, where there may be a delay in making the diagnosis or initiating treatment. Sending samples to a national laboratory for genetic analysis takes time and can delay recognition of APL. In one of its first projects, the team found that an antibody against the promyelocytic leukemia protein (anti-PML) diagnosed the disease with a sensitivity and specificity of nearly 99%. In addition, the test could return results in fewer than 6 hours, at little cost, and could be made available in a broad range of clinical settings.6
Next, the IC-APL researchers tackled treatment protocols; they needed to develop a course of treatment that would be both cost-effective and accessible to most treatment centers, even small centers. Patients with APL in the U.S. and Europe often are treated with a combination of ATRA and arsenic trioxide, and sometimes idarubicin is added. But, to lower treatment costs and ensure that all the necessary drugs were available at facilities across Brazil, the team modified the protocol to include ATRA combined with a different chemotherapeutic agent, daunorubicin, and without arsenic.
The initiative was reported to be highly successful, leading to 2-year overall survival rates of 80% – a 30% percent increase from baseline values.
Dr. Rego attributes this improvement to international collaboration. "The impact of networking cannot be overstated," he said. "We have been able to move much faster than we would without the support."
Following the program's initial successes, the IC-APL expanded to encompass acute myeloid leukemia (AML), becoming the International Consortium on Acute Leukemias (ICAL). Consortium members in other Latin American countries such as Chile, Paraguay, Peru, and Uruguay, are building registries to collect local patient data.
"We have two main goals," said Dr. de Figueiredo Pontes, who is an ICAL coordinator for the RibeirÃ£o Preto Medical School at the University of SÃ£o Paulo. "One, this registry information will provide us with epidemiological data involving AML, as well as outcomes data. Two, we want to enroll more patients. We now have 10 centers involved in the study, all of which are using the same treatment strategy, and a central laboratory that is performing all the diagnostics."
Ideally, this information will help researchers better understand the epidemiology and treatment of AML in these Latin American countries. Like IC-APL did for APL, ICAL participants are hoping to develop protocols that can be adapted to different countries' health care systems and levels of access.
Still, some entrenched problems will be difficult to solve, even with the assistance of international networks. The three physicians who spoke with ASH Clinical News agreed that country's two-tier health care system is a major contributor to the disparity in the treatment of blood cancers in Brazil.
For example, it is not only access to new drugs to treat hematologic malignancies that needs to be improved; patients also need access to more modern supportive care drugs such as newer antifungal treatments to manage opportunistic infections that arise during treatment, Dr. Rego said. He believes that lack of access to these drugs may be increasing the length of time a patient needs to stay in the hospital.
Dr. Maiolino, who chairs ABHH's Medicine Access Committee, added that he is currently working with ABHH members, pharmaceutical companies, and other stakeholders in Brazil to erase disparities for patients in the public and private health systems. It will be a challenge, but, he said, "our group is committed to solving this problem." â€”By Emma Yasinski
- Ades F. Access to oncology drugs in Brazil: juggling innovation and sustainability in developing countries. Medicine Access @ Point of Care. 2017 January 19.
- World Health Organization. International Agency for Research on Cancer: Brazil. Accessed July 14, 2020, from https://gco.iarc.fr/today/data/factsheets/populations/76-brazil-fact-sheets.pdf.
- Global Health Intelligence. "Brazil Hospital Demographics 2016 – Latin America's Second Largest Hospital Market Can Still Gain Efficiencies." Accessed July 14, 2020, from www.globalhealthintelligence.com/ghi-analysis/brazil-hospital-demographics-2016-latin-americas-second-largest-hospital-market-can-still-gain-efficiencies/.
- da Silva MJS, O'Dwyer G, Osorio-de-Castro CGS. Cancer care in Brazil: structure and geographical distribution. BMC Cancer. 2019;19:987.
- Chieffi AL, Barradas RDCB, Golbaum M. Legal access to medications: a threat to Brazil's public health system? BMC Health Serv Res. 2017;17:499.
- Koury LCDA, Ganser A, Berliner N, Rego EM. Treating acute promyelocytic leukaemia in Latin America: lessons from the International Consortium on Acute Leukaemia experience. Br J Haem. 2017;177:979-983.