Introduction

Lung cancer is a global public health problem. It represents the first cause of cancer-related deaths around the globe, both in developed as well as developing countries, and mortality in the future is expected to increase substantially.¹1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. https://doi.org/10.3322/caac.21492
https://doi.org/10.3322/caac.21492... ^,22. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941-53. https://doi.org/10.1002/ijc.31937
https://doi.org/10.1002/ijc.31937... Recently, lung cancer is reported to cause 2.07 million deaths each year; this amount is expected to almost double to three million by 2035. Importantly, 16% of the global deaths from lung cancer occur in the Americas region, a number which is also expected to double from 262 314 deaths reported in 2012, to 501 860 by 2035. These alarming figures highlight the need to battle this tendency.³3. Didkowska J, Wojciechowska U, Manczuk M, Lobaszewski J. Lung cancer epidemiology: contemporary and future challenges worldwide. Ann Transl Med. 2016;4(8):150. https://doi.org/10.21037/atm.2016.03.11
https://doi.org/10.21037/atm.2016.03.11...

In Mexico the outlook is also somber; lung cancer claims more lives than any other malignant disease, with an average of 6 678 annual deaths.⁴4. Mohar-Betancourt A, Reynoso-Noveron N, Armas-Texta D, Gutierrez-Delgado C, Torres-Dominguez JA. Cancer trends in Mexico: Essential data for the creation and follow-up of public policies. J Glob Oncol. 2017;3(6):740-8. https://doi.org/10.1200/JGO.2016.007476
https://doi.org/10.1200/JGO.2016.007476... In spite of the highly relevant burden of disease, globally as well as nationally, lung cancer patients still suffer from inequities in the access to healthcare. In this context, equity is understood as the absence of unfair or remediable differences among groups of people who vary in terms of social, economic, demographic or geographic determinants. As such, health equity therefore conceptualizes that everyone must have the same opportunity to achieve their full health potential. Further, health equity must be understood and measured as services provided (and not necessarily the population´s health condition). Therefore, health equity can be achieved when equal services are provided to the entire population.⁵5. Penman-Aguilar A, Talih M, Huang D, Moonesinghe R, Bouye K, Beckles G. Measurement of health disparities, health inequities, and social determinants of health to support the advancement of health equity. J Public Health Manag Pract. 2016;22(suppl 1):S33-42. https://doi.org/10.1097/PHH.0000000000000373
https://doi.org/10.1097/PHH.000000000000... ^,66. Farrer L, Marinetti C, Cavaco YK, Costongs C. Advocacy for health equity: a synthesis review. Milbank Q. 2015;93(2):392-437. https://doi.org/10.1111/1468-0009.12112
https://doi.org/10.1111/1468-0009.12112... ^,77. World Health Organization. Health topics, Health equity, c2018 [cited 2019 March 1]. Available from:Available from:https://www.who.int/topics/health_equity/en/
https://www.who.int/topics/health_equity...

Overall, lung cancer programs face many challenges towards closing the inequity gap. For example, contrary to other common malignancies, there is currently no active public screening program for high-risk populations in Mexico; even though the main risk factors leading to this malignancy within the region, including tobacco and wood-smoke exposure, are well characterized.⁸8. Raez LE, Nogueira A, Santos ES, Dos Santos RS, Franceschini J, Ron DA, et al. Challenges in lung cancer screening in Latin America. J Glob Oncol. 2018(4):1-10. https://doi.org/10.1200/JGO.17.00040
https://doi.org/10.1200/JGO.17.00040... ^,99. Arrieta O, Lopez-Mejia M, Macedo-Perez EO, Corona-Cruz JF. Proposals for the prevention of lung cancer in the health system of Mexico. Salud Publica Mex. 2016;58(2):274-8. https://doi.org/10.21149/spm.v58i2.7796
https://doi.org/10.21149/spm.v58i2.7796... High-risk subjects have the option of paying for screening studies, however these are costly and only available in certain centralized areas, creating a wide gap, due to demographic and economic determinants, in terms of achieving a timely diagnosis. Interestingly, in 2019 the government expects to collect a total revenue from tobacco taxation of 43 078.9 million (MXN), and these resources could very logically be directed towards this patient population.¹⁰10. Secretaría de Hacienda y Crédito Público. Paquete Económico para el Ejercicio Fiscal 2019, c2018 [cited 2019 March 1]. Available from: Available from: https://www.ppef.hacienda.gob.mx/ On the contrary, lung cancer is the only high-mortality malignancy without coverage by the popular security insurance Seguro Popular. As such, lung cancer patients face late-stage diagnoses, due to a lack of screening, and restricted, if any, therapies available to them. Consequentially, lung cancer kills more people in Mexico than any other malignant disease.

The characteristics of the lung cancer epidemic in Mexico have been characterized in previous studies, and therefore this paper will focus on the important subject of access to lung cancer therapy for Mexican patients, highlighting opportunities for greater equity within the health system.

The Mexican public healthcare sector

Mexico’s healthcare system is a complex subset of institutions, mostly derived from public policies, though a private sector also exists. The Ministry of Health (MoH) is in charge of governance, health policies, public health, financing and highly specialized healthcare, and oversees the actions taken by the local health secretariats of the MoH which serve in each of the 32 Mexican states. Under the MoH governance, several institutions exist, which affiliate the individuals according to their job status (employed in the formal market or not), rather than by their health needs (not their economic necessity). Though it certainly has achieved several public health milestones, this fragmented system has often proven to be complex, unequal and many times inefficient in dealing with non-transmissible diseases. Subjects might be affiliated to several systems at the same time, and real-time electronic patient records are still unavailable, making cross-talk between previous and current physicians challenging, to say the least.¹¹11. Organization for Economic Cooperation and Development. OECD Reviews of Health Systems: Mexico 2016. Paris: OECD, 2016. Further, Mexico is lagging behind in terms of compiling a robust database with the objective of registering the cancer cases diagnosed throughout the country. On July, 2018 the Federation’s Official Newsletter released information regarding the nascent program for a national cancer registry, which would have the objective of integrating cancer cases information in order to provide consistent, complete and opportune information for use in research, resource allocation and development of public policies in this matter. Results will be published online yearly by the National Cancer Institute (INCan), and it is certain that this information will improve our current understanding of cancer epidemiology in the nation, helping to assess the problematic through a unified perspective. Public sector healthcare providers and programs include, in order of highest-to-lowest affiliated members, the Instituto Mexicano del Seguro Social (IMSS), Seguro Popular (SPS), Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Petróleos Mexicanos (Pemex), Secretaría de la Defensa (Sedena), and Secretaría de Marina (Semar).¹²12. Gómez-Dantés O, Sesma S, Becerril VM, Knaul FM, Arreola H, Frenk J. Sistema de salud de México. Salud Publica Mex. 2011;53(suppl 2):s220-32. https://doi.org/10.1590/S0036-36342011 000100016
https://doi.org/10.1590/S0036-36342011 0... Increasing the complexity of the matter, each dependency has a master catalogue of approved medications, each with their particular indications and presentations, therefore therapeutic schemes might vary across the healthcare system due to lack of the proper supplies or the means to enforce adherence, which impedes the establishment of nation-wide standards of care for this particular neoplasm. Altogether, the structure of the healthcare system as it currently is makes it difficult to promote the provision of equitable services for lung cancer patients.

Basic interinstitutional catalogue of medications

The General Health Counsel is a multidisciplinary organism, which is in charge of creating, updating and publishing the basic list of supplies for the first, second and third level of attention. Through eight specific committees, this counsel incorporates scientific and technologic advances in medicine, in the form of a master “Essential Interinstituional Catalogue of Medications”, in order to encourage the rational use of quality supplies in the public institutions of the National Health System. In 2016, an updated version of the master catalogue for basic and higher-level care medications was released by this interinstitutional committee in an effort to harmonize the catalogues from the different institutions. In this document, the 17^th group is comprised of Oncologic medications, including 114 currently approved and available drugs throughout the different health providing institutions. Interestingly, lung cancer has only 14 drugs as therapeutic options. Moreover, among these 14 drugs, four of them are obsolete in the current guidelines for the management of lung cancer patients, due to lack of efficacy and high toxicity profiles (cyclophosphamide, doxorubicin, ifosphamide and mitomycin). This leaves only 10 options, among which two are standard first line treatment options for Non-small cell lung cancer (NSCLC) (carboplatin/pemetrexed) and four other are second line NSCLC options (Docetaxel, gemcitabine, vincristine, vinorelbine), there is one treatment option for small cell lung cancer (etoposide). All the above-mentioned treatments are based on chemotherapy and are recommended for patients with advanced-stage disease who do not have actionable mutations or who are not candidates for immune checkpoint inhibitors. Meanwhile, only three drugs included in this catalogue are targeted therapy agents, including one tyrosine kinase inhibitor (TKI) for patients with rearrangements in the Anaplastic Lymphoma Kinase gene (ALKr), and two TKIs for patients with sensitizing mutations in the Epidermal Growth Factor Receptor gene (EGFR). Unfortunately, all these targeted therapies (crizotinib, erlotinib and gefitinib) are first-generation drugs, which have considerable limitations in terms of their long-term effectiveness and pharmacokinetic profile (such as central nervous system penetration). Meanwhile, second and third generation drugs, including afatinib, osimertinib, alectinib among others, have managed to circumvent these limitations and offer patients better survival outcomes, however none of these are included in the catalogue.¹³13. Comisión Interinstitucional del Cuadro Básico y Catálogo de Insumos del Sector Salud. Cuadro Básico y Catálogo de Medicamentos. Ciudad de México: Consejo de Salubridad General, 2016. Available from:http://www.csg.gob.mx/descargas/pdf/priorizacion/cuadro-basico/med/catalogo/2016/EDICION_2016_MEDICAMENTOS.pdf
http://www.csg.gob.mx/descargas/pdf/prio...

Another important limitation in the currently approved list of medications is the lack of immunoncology (IO) agents, which are changing the paradigm of advanced lung cancer treatment in the current age. Several large-scale clinical trials have found that in a subgroup of advanced NSCLC patients, the use of IO increases progression-free and overall survival, reducing the risk of death by more than 40% compared to chemotherapy.¹⁴14. Qin H, Wang F, Liu H, Zeng Z, Wang S, Pan X, et al. New advances in immunotherapy for non-small cell lung cancer. Am J Transl Res. 2018;10(8):2234-45.Aside from their improved survival outcomes, studies have assessed the cost-effectiveness of these agents, finding them cost-effective in the United Kingdom, however such data within Mexico’s regional setting is lacking.¹⁵15. Georgieva M, da Silveira-Nogueira-Lima JP, Aguiar P Jr, de Lima-Lopes G Jr, Haaland B. Cost-effectiveness of pembrolizumab as first-line therapy for advanced non-small cell lung cancer. Lung Cancer. 2018;124:248-54. https://doi.org/10.1016/j.lungcan.2018.08.018
https://doi.org/10.1016/j.lungcan.2018.0...

Last, it is important to highlight that many of the medications which are covered by this catalogue and applied at most of the public health institutions are free of charge, and there is no copayment at the point of care. This is particularly important when considering the costs associated with lung cancer care for patients in Mexico, which ranges from 47 858.00 to 393 934.06 MXN, varying depending on disease stage. All of these costs are therefore absorbed by the institution when the patient is insured by IMSS, ISSSTE, PEMEX, Sedena or Semar. For patients who are not affiliated to the previous institutions, or who have SPS, costs associated with this disease imply a catastrophic expenditure, and therefore it is imperative that government instances solve the issue of access to treatment for these patients, who most of the time do not have the economic resources required for therapy.

Discrepancies in lung cancer care across health institutions

As previously mentioned lung cancer de facto standard-of-care varies in Mexico and depends on the health institution to which each patient is affiliated. In table I a short overview of some of the most important needs to be met by a lung cancer oncology service are listed, and then reviewed by their availability within the major health institutions in the country. We review availability also in the private sector and the National Cancer Institute (Incan), as well, which is a nation-wide reference center for this malignancy.

The information presented here can be interpreted in myriad ways, however one of the most straightforward affirmations that can be made from this table is the fact that the sector of the population most well-equipped for facing a lung cancer case is that which holds a private medical insurance service. Unfortunately, in Mexico, less than 7% of the population has private health insurance. On the other hand, the most vulnerable population in terms of lung cancer care is that which is affiliated to Seguro Popular, or popular health insurance (PHI) which arose as an initiative that sought, in a period of seven years, to offer health insurance to over 50 million people who at the time where not affiliated to any health service.¹⁶16. Tamez-Gonzalez S, Eibenschutz C. El Seguro Popular de salud en México: pieza clave de la inequidad en salud. Rev Salud Publica. 2008;10(suppl 1):133-45. https://doi.org/10.1590/S0124-00642008000600012 Currently, over 54 million Mexicans have PHI, and though this ambitious initiative has managed to reduce catastrophic health expenditure in homes nationwide by up to 46.5%,¹⁷17. Avila-Burgos L, Servan-Mori E, Wirtz VJ, Sosa-Rubi SG, Salinas-Rodriguez A. Efectos del Seguro Popular sobre el gasto en salud en hogares mexicanos a diez años de su implementación. Salud Publica Mex . 2013;55(suppl 2):S91-9. https://doi.org/10.21149/spm.v55s2.5103
https://doi.org/10.21149/spm.v55s2.5103... the program has some severe limitations. Ultimately, what is perhaps the most pressing concern is the fact that standard-of-care for lung cancer patients should be dictated by the scientific literature available, in order to produce the most state-of-the art guidelines for these patients. Counter to this, in the practical sense lung cancer care in Mexico is currently dictated by the institution which affiliates the patient, the available resources for treatment, and the access to the facilities which have the infrastructure and personnel to treat this disease. Currently, the first five causes of cancer-related deaths in Mexico include, in descending order, lung, breast, colon, prostate, cervix. Even though lung cancer tops this list, this is the only one out of the five malignancies that is not covered by the FPGC (Fund for protection against catastrophic expenditures) of the PHI. Also, other sources of financing must be available in order to treat cancer, including current costs, infrastructure, surgery, diagnostic supplies and other costs (table II), which are covered by the MoH.¹⁸18. Comisión Nacional de Protección en Salud. Catálogo Universal de Servicios de Salud. Mexico City: Secretaría de Salud, 2018.This is a severe impairment, especially when considering that lung cancer treatment costs are usually associated with catastrophic health expenditure when patients are not covered by health insurance.¹⁹19. Lu Y, Cheng J, Lin Z, Chen Y, Xuan J. Pharmacoeconomic analysis for pemetrexed as a maintenance therapy for NSCLC patients with patient assistance program in China. J Med Econ. 2018;21(1):60-5. https://doi.org/10.1080/13696998.2017.1373654
https://doi.org/10.1080/13696998.2017.13... Furthermore, previous studies have determined that in NSCLC there is a direct association between expenditure allowance and survival, in which patients have a significantly reduced risk of dying when they have access to a greater fund in order to treat the disease. In contrast, such association has not been found in the case of breast or renal carcinoma, nor in chronic myeloid leukemia.²⁰20. Baumgardner J, Shahabi A, Linthicum M, Vine S, Zacker C, Lakdawalla D. Greater spending associated with improved survival for some cancers in OCM-Defined episodes. J Manag Care Spec Pharm. 2018;24(6):504-13. https://doi.org/10.18553/jmcp.2018.24.6.504
https://doi.org/10.18553/jmcp.2018.24.6....

Opportunities and adversities to tackle

A new era for cancer treatment emerged in 2011, transforming patient therapy through a deeper understanding of tumor biology and novel drugs which target specific pathways within or around the tumor cells. All these factors, in addition to improved diagnosis and access to treatment, have produced a steady decline in cancer mortality within developed nations, including France, Japan, and the United States. Life expectancy for lung cancer patients has therefore benefitted from these advances in molecular biology and technology, positively impacting the outlook for a population which at many times is economically productive. Nonetheless, this declining mortality is also related to access to treatment, and therefore developing nations with less availability of novel therapeutic options might be lagging behind.²¹21. QuintilesIMS Institute. Global Oncology Trends 2017. Advances, Complexity and Cost. Parsippany, NJ: QuintilesIMS Institute, 2017. Since 2011, 11 new drugs have been launched globally for the treatment of lung cancer, encompassing agents for actionable mutations (TKIs) and immune checkpoint inhibitors. The use of novel therapies has forever changed the outlook for lung cancer patients, providing durable responses and better safety profiles, and is expected to further improve as new drugs emerge from the pipeline and as current ones gain approval within the first-line setting.²¹21. QuintilesIMS Institute. Global Oncology Trends 2017. Advances, Complexity and Cost. Parsippany, NJ: QuintilesIMS Institute, 2017. Furthermore, ongoing clinical trials are stratifying patients in order to adequately find the subgroup which might reap the most benefit from each new agent, emphasizing the transition towards the era of personalized medicine. The question will now be: Who will have access to these therapies? In a resource-limited setting, such as Mexico and Latin America, the answer will likely be those wealthy enough to have costly private health insurance services. Our most economically vulnerable population will continue to rely on their very scarce financial resources, and will therefore not reap any benefit from all this wealth of knowledge and options. In a country which states that health is a constitutional right, it is difficult to not find this disturbing. The current pipeline for oncology drug development is overwhelmed by target molecules and target biologic agents, both of which remain underrepresented within our public health system even though they bring the best outcomes and have been shown to be cost-effective.²²22. Lu S, Ye M, Ding L, Tan F, Fu J, Wu B. Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China. Oncotarget. 2017;8(6):9996-10006. https://doi.org/10.18632/oncotarget.14310
https://doi.org/10.18632/oncotarget.1431... ^,2323. Ting J, Tien-Ho P, Xiang P, Sugay A, Abdel-Sattar M, Wilson L. Cost-effectiveness and value of information of erlotinib, afatinib, and cisplatin-pemetrexed for first-line treatment of advanced EGFR mutation-positive non-small-cell lung cancer in the United States. Value Health. 2015;18(6):774-82. https://doi.org/10.1016/j.jval. 2015 .04.008
https://doi.org/10.1016/j.jval. 2015 .04... ^,2424. Carlson JJ, Suh K, Orfanos P, Wong W. Cost Effectiveness of alectinib vs. crizotinib in first-line anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer. Pharmacoeconomics. 2018;36(4):495-504. https://doi.org/10.1007/s40273-018-0625-6
https://doi.org/10.1007/s40273-018-0625-... The challenges and opportunities now facing Mexico’s health system in terms of lung cancer must be addressed-it is ever so important that we tackle the issue of treatment inequity, and work to reverse the fact that more than 90% of the country’s population will not benefit any time soon from the latest breakthroughs in lung cancer science. In addition to the lack of last-generation therapies, Mexico’s bureaucracy many times delays the approval and implementation of clinical trial protocols which could admit patients and offer them options unavailable to them otherwise. Such barriers must be sorted in order to make this system more efficient and therefore benefit from recruiting clinical studies. In addition, this would also help increase the representation of Hispanic patients throughout the current body of scientific knowledge, optimizing the safe implementation of therapies which are generally approved with data from Caucasian or Asian patients. Another important opportunity is the creation of unified treatment guidelines, facilitating patient management and decreasing associated costs and complexity. This is highly relevant as oncologists are more than ever dealing with chronicity and such trend is expected to continue in the nearby future. Government policy makers must realize the widening breach which faces lung cancer patients from different socioeconomic backgrounds. The poorest of our country should not have to be in danger of dying from lung cancer.

References

Publication Dates

History