The joys of jet lag and working in different time zones: as the sun rises at 6 AM, I feel like it is 9 AM. With nearly 3 hours to spare before the conference starts, I go for a run. Crossing the threshold for the beach and leaving behind the resort (and the crows having an early morning feast from what humans left behind in the lawn and outside patio the night before), I am rewarded with a sight of Playa Bonita, the pretty beach. The sound of the surf mildly breaking and rolling into the coarse sand, peppered with sea shells and even a few scattered starfish, unusual so close to an urban center these days, almost makes me think I'm here on holiday. At the first bend, as I look out to the ocean for a moment, I have déjà vu and my mind floats back to Singapore. But here the scores of cargo ships slowly making their way through the Pacific are actually headed to the canal, for I am in Panama for the 2016 International Association for the Study of Lung Cancer’s (IASLC) Latin American Conference on Lung Cancer.

Still running on the beach, once I steady my bearings, landing with my whole sole rather than just the heels, and stop sinking into the compacted sand and scaring the locals (crabs running into their holes), I go back to auto-pilot and start thinking of the week ahead.

Colleagues from around the region and the globe are here to discusslLung cancer, the deadliest cancer worldwide, and a particular concern for Latin America. The rising incidence poses significant challenges for the region, which struggles with limited resources to meet the health care needs of its low- and middle-income populations. While tobacco control has been exemplary in some countries in Latin America, health care decision- and policy-makers in government, social, and private sectors are still relatively unaware of the pressing need to implement effective strategies for the prevention, screening, diagnosis, and treatment of lung cancer. The region has also been slow in adopting molecularly based therapies in the treatment of advanced disease. Testing for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangements are the exception rather than the rule, and access to targeted agents such as monoclonal antibodies and tyrosine kinase inhibitors is problematic. In a recent paper,¹ we reviewed the current situation in the control and management of lung cancer in Latin America, hoping that this initiative will help physicians, patient support and advocacy groups, industry, governments, and other stakeholders start facing this epidemic.

By 2030, the number of deaths due to lung cancer is expected to almost double for Latin American women and to increase by 50% for men. Despite strong action against tobacco, through legislation restricting sales and advertising, increasing taxation, establishing smoke-free indoors public policies, educational campaigns, public control programs to prevent teenage and young adult smoking, and therapeutic programs to increase quitting, the epidemiologic impact of lung cancer is still high and rising. There is particular concern in low-income populations in which smoking is still highly prevalent and more commonly so, as well as associated with a heavy economic burden. Cigarettes can represent between 25% and 40% of all expenditures of low-income families and individuals in the region.

In Latin America and low- and middle-income countries around the world, most governments and health systems have evolved to address infectious diseases and maternal-child health, for a long time ignoring the demographic transition and the significant increase in the incidence of chronic non-communicable diseases, including lung cancer. Early detection programs are usually absent, and when available, are often ineffective and restricted to the private sector and wealthier segments of the population. Cancers are therefore commonly diagnosed at later stages with correspondingly high mortality and suffering. Treatment for late-stage cancers most commonly takes place in public hospitals that have limited resources due to a combination of poor funding and oversized demand for services. As a result, often health care institutions can only provide a bare minimum of activities that cannot keep up with an overwhelming load, compromising results. Many countries also lack basic cancer planning tools such as population-based cancer registries, up-to-date clinical guidelines, and consistent coverage and provision of care.

Older chemotherapy agents available as generics, such as cis- and carboplatin, gemcitabine, and taxanes, are commonly used, but there is limited access to molecular testing, modern staging procedures, and targeted agents and immunotherapy. Around 25% of patients in Latin America and Hispanic patients in the United States have EGFR-activating mutations, a higher prevalence than in white patients in North America and Europe, making the lack of availability of targeted agents an even bigger failure.

A handful of miles away from the hotel is the Bridge of the Americas, a feat of engineering tall enough to allow the New-Panamax ships, leviathans of global trade measuring 3.5 times the length of a football field, to pass underneath it on their way to the new canal locks. (If you are curious, these vessels can carry up to 12,000 20-foot containers, which could hold the usual items of 12,000 1,200-square-foot apartments.) Beyond the bridge lies Panama City, Central America’s response to Singapore and Hong Kong.  As Steve Forbes wrote in 2016, mention Panama and the first thing to come to mind might be “papers” and money laundering, but the country’s sustained GDP growth in the last decade makes this the unsung success story in a region that has been plagued by setbacks in recent years. Through efforts in transparency (the Organization for Economic Co-Operation and Development, OECD, recently removed Panama from its list of tax havens), and business-friendly policies such as a low tax environment, decreased bureaucracy, and welcoming foreigners and their investments, the country is well poised to continue growing and to become a model for many in Latin America. This brings hope that with continued development, the region will be able to double down on its efforts against lung cancer.

Civil society action is increasingly common in low- and middle-income countries. In Mexico and Brazil, among others, advocacy activities through non-government organizations have started to develop networks of cancer survivors that help provide emotional and practical support, as well as, together with professional societies and other stakeholders, to lobby governments for action, including access to diagnostic tests and treatments for cancer.² Moreover, many individuals in Brazil and Colombia sue their governments to gain access to more expensive treatments that are otherwise available only to privately insured citizens.³ Most patients who sue the state in these two countries win their cases. However, these are usually individuals who are wealthy enough to hire lawyers, compounding the inequity that already exists in health systems in the region. Critics have also argued that if public providers included these medications, governments could negotiate better prices with pharmaceutical companies through price discrimination, volume-based agreements, and joint or consortium-based purchasing. As an example, Brazil recently teamed up with Paraguay, Argentina, and Uruguay so that those countries could benefit from the 80% to 90% discounts it obtained for hepatitis C medications, bringing costs per treatment down from nearly US$100,000 to less than US$10,000. It is outside of the scope of this piece to discuss other options to increase access to cancer medications in lower-resource settings but readers are welcome to check the references listed for a deeper discussion on the subject.⁴

For patients who do not have targetable molecular alterations, immune check point inhibitors targeting the PD-1/PD-L1 axis bring new hope of longer disease control and survival. This, however, has come at a very high cost. One of the papers we were scheduled to present in Panama (updated at the 2016 IASLC World Conference on Lung Cancer⁵) calculated that the cost of treating all potentially eligible patients with non-small cell lung cancer in the second line in Brazil would amount to US$173 million, approximately 20% of all current expenses in cancer drugs in the country. Blatantly unaffordable, these results are due to the nearly equal price of the drug in Brazil and the United States and other developed countries. For now, the medication is only available for the 25% of Brazilians who have private medical insurance. We also showed that, as imperfect as it is, PD-L1 expression could help rationalize treatment and expenses, through the selection of patients most likely to benefit from these drugs. We calculated that if only patients with 50% or greater expression were treated, the cost of giving pembrolizumab to all eligible patients would be US$43 million (still unaffordable, but 75% lower and a good place to start price negotiations).

A sign reading “Crocodiles Live in this Area, Stay Away” sends me back to the hotel, effectively ending my run. If immunotherapy and targeted agents live up to their promise and patients truly benefit from long-term disease control, it will be difficult to hold a tide of patients and advocates claiming for right to treatment use of compulsory licenses.⁶ The writing is on the wall.

References

1. Raez LE, Santos ES, Rolfo C, et al. Challenges in facing the lung cancer epidemic and treating advanced disease in Latin America. Clin Lung Cancer. 2017;18:e71-e79.
2. Fonseca EM, Bastos FI, Lopes G. Increasing access to oral anticancer medicines in middle-income countries: a case study of private health insurance coverage in Brazil. Journal of Global Oncology. 2016;2:39-46 .
3. Lopes G, Prado E, Montero AJ. Suing the state for access to cancer medications: The Brazilian experience. J Clin Oncol. 2015;33 (suppl, abstr e17566).
4. Lopes Gdel Jr, de Souza JA, Barrios C. Access to cancer medications in low-and middle-income countries. Nat Rev Clin Oncol. 2013;10:314-22.
5. Aguiar P, De Mello R, Tadokoro H, et al. An estimate of the economic impact of immunotherapy relative to PD-L1 expression in Brazil - an update with Brazilian costs. Journal of Thoracic Oncology 2017;12 (suppl, S427).
6. Bognar C, Bychkovsky BL, Lopes G. Compulsory licenses for cancer drugs: does circumventing patent rights improve access to oncology medications? Journal of Global Oncology. 2016;2:292-301.