Originally printed in ASCO Daily News; republished with permission.

The joys of jet lag and working in different time zones: as the sun rose at 6 AM, I felt like it was 9 AM. With nearly 3 hours to spare before the conference started, I went for a run. Crossing the threshold for the beach and leaving behind the resort, I was 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 seashells and even a few scattered starfish, unusual so close to an urban center these days, almost made me think I was here on holiday. At the first bend, as I looked out to the ocean for a moment, I had déjà vu and my mind floated back to my former life in Singapore. However, the scores of cargo ships slowly making their way through the Pacific were actually headed to the canal, for I was in Panama for the 2016 International Association for the Study of Lung Cancer (IASLC)’s Latin America Conference on Lung Cancer.

Still running on the beach, once I steadied my bearings, landing with my whole sole rather than just the heels and stopped sinking into the compacted sand and scaring the locals (crabs running into their holes), I went back to autopilot and started thinking of the week ahead.

Colleagues from around the region and the globe were in Panama to discuss lung cancer, the deadliest malignancy worldwide, particularly 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. Although tobacco control has been exemplary in some countries in Latin America, health care decision-makers and policymakers 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 EGFR mutations and ALK 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, 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 face this epidemic.¹

By 2030, the number of deaths due to lung cancer is expected to almost double for Latin American women and increase by 50% for men.¹ Despite strong action against tobacco—such as legislation restricting sales and advertising, increased taxation, establishing smoke-free indoors public policies, education 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 noncommunicable 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. Therefore, cancers are 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 because 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 that are available as generics are commonly used, such as cisplatin and carboplatin, gemcitabine, and taxanes, but there is limited access to molecular testing, modern staging procedures, and targeted agents and immunotherapy. Approximately 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.^2,3

Economics and Civil Action

A handful of miles away from my conference 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. 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,⁴ 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 Organisation for Economic Co-operation and Development recently removed Panama from its list of tax havens⁵) 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 nongovernment organizations have started to develop networks of cancer survivors that help provide emotional and practical support. Additionally, together with professional societies and other stakeholders, they have started to lobby governments for action, including access to diagnostic tests and treatments for cancer.⁶ 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.⁷ 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 $100,000 to less than $10,000.⁸

The Cost of Treatment

For patients who do not have targetable molecular alterations, immune checkpoint 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 presented in Panama (and later published in Annals of Oncology) calculated that the cost of treating all potentially eligible patients with non–small cell lung cancer in the second-line setting in Brazil would amount to $173 million, approximately 20% of all current expenses in cancer drugs in the country.^9,10 Blatantly unaffordable, these results are due to the nearly equal price of the drug in Brazil and the United States and other upper-income countries. For now, the medication is only available to the 25% of Brazilians who have private medical insurance.¹¹

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 $43 million (still unaffordable, but 75% lower and a good place to start price negotiations).

Fast forward a year and a half, and I again found myself running, this time in California in February 2018. A couple of miles north of Santa Monica, on one of the hills over the Pacific Coast Highway, I gazed at an old oak tree that stood tall, alone. At the beach, scores of surfers tried their luck in the short surf and slightly above freezing waters. Again, I was running to fight jet lag after getting up at the local 2:00 AM, my usual East Coast waking hour.

Attending the IASLC 18th Lung Cancer Targeted Therapies Meeting, at which my colleagues and I presented a large number of ongoing trials that are likely to set new standard therapies, bringing hope to patients who can afford them, made me think of Latin America once more. In August 2018, lung cancer physicians, researchers, and advocates will meet again at the IASLC Latin America Conference on Lung Cancer, and access and affordability will be high on the agenda.

The region has come a long way since the 1970s, when military dictatorships shackled individual liberties, and the 1980s, when the second oil crisis and rapidly increasing prices led to a debt crisis and one of the worst recorded recessions, which dropped hundreds of millions of people below the poverty line from Mexico to Argentina and spared very few countries in between. Societies have become more democratic and governments more responsive to the demands of their citizens. 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.¹¹ The writing is on the wall. I hope you join us in Argentina.

References

1. Raez LE, et al. Clin Lung Cancer. 2017;18:e71-e79.
2. Arrieta O, et al. J Thorac Oncol. 2015;10:838-43.
3. De Barros Pontes L, et al. J Clin Oncol. 2014;32 (suppl; abstr 1526).
4. Forbes S. Forbes. The Panama Papers? Here’s the Real Panama Story. forbes.com/sites/steveforbes/2016/05/10/the-real-story-about-panama/
   #57b87f4f39f6. Published May 10, 2016. Accessed March 5, 2018.
5. Durieu H, et al. Vandelanotte. Filing obligation for payments to tax havens: OECD list updated. vandelanotte.be/en/nieuws/so16-11-22-aangifteplicht-betalingen-aan-belastingparadijzen-oeso-lijst-geupdatet/.Accessed March 5, 2018.
6. Fonseca EM, et al. J Glob Oncol. 2016;2:39-46.
7. Lopes G, et al. J Clin Oncol. 2015;33 (suppl; abstr e17566).
8. Lopes G, et al. Nat Rev Clin Oncol. 2013;10:314-22.
9. Aguiar P, et al. J Thorac Oncol. 2017;12 (suppl; S427).
10. PN Aguiar Jr, et al. Ann Oncol. 28:2256-63.
11. Bognar C, et al. J Glob Oncol. 2016;2:292-301.