MTE28.01 Implementation of Precision Medicine in Routine Practice: The Latin American Experience

Abstract

Technology for molecular testing in lung cancer is a highly demanding aspect to tackle in the LATAM countries. Molecular testing requires incorporation of new technologies usually involving expensive equipment, reagents and supplies. Moreover, these items are commonly imported from other countries and are subjected to custom regulation and heavy taxes. Therefore, LATAM labs commonly face unpredictable delays in the legal processing of purchase orders, are constantly adjusting to changes in regulations and in the country’s financial status, and suffer from slow and sometimes poor support from companies that do not see them as preferred clients. As an example of consequences of some of these points, in Argentina the agents Nivolumab and Pembrolizumab were approved by government agencies for immunotherapy for NSCLC before the molecular testing laboratories had conditions to purchase the DAKO platform and the CDx antibodies for appropriate IHC testing. Some technical devices such as automated IHC platforms are more widely available. They were initially integrated onto large pathology labs in the main cities of several countries but smaller automated platforms are currently available in a number of other cities. There are laboratories equipped for fluorescence in situ hybridization (FISH) and for DNA sequencing in most countries. Sanger sequencing is still commonly used, but the main laboratories already incorporated newer technologies such as RT-PCR allele-specific technology (usually Cobas platform) and tailored panels of next generation sequencing (NGS) or have them in the short list for implementation. Additionally to the challenges in the laboratories organization, two other main issues obstruct the implementation of lung cancer molecular testing in the LATAM countries: the lack of a stable logistic infra-structure necessary to ship biological samples to the molecular laboratories in a cheap, reliable and rapid way, and the hurdle of cost reimbursement for the tests. In the past 10 years, expenses and logistics for transfer of biological specimens and reimbursement for molecular test costs, in most countries such as Mexico, Brazil and Argentina, were sponsored by pharmaceutical companies. Companies such as AstraZeneca, Roche, Boehringer Ingelheim, and Pfizer have acted through clinical trials or special access programs. In a smaller scale, molecular tests have been supported by governmental health agencies or covered by private health care insurance companies. A restricted number of patients are paying the tests out of the pocket, mostly sending to US laboratories. Least but not least, the implementation of lung cancer molecular testing relies in the adequate quantity and, most importantly, in the good quality of the available biological sample. Subsequent to the intense interdisciplinary work by the laboratory personnel, significant progress has been detected in the last years in the amount of tumor cells present in the testing specimens. However, proper quality is only achieved in a fraction of specimens. Most LATAM countries do not have local regulations for quality control (QC) of pathology laboratories, and a limited number of those laboratories are taken external QC certification. Moreover, there is no financial support for the adequate validation of the assays at their implementation and for the competency checking periodically thereafter. In consequence, the risk of having laboratories testing in substandard quality conditions is high. Institutions that are well-structured administratively, technically and scientifically and that handle large volumes of clinical specimens usually participate in external QC for molecular tests. They engage in accredited proficiency testing activities or, at least, send material to reference laboratories for investigation of reproducibility of results. Unfortunately, this does not occur in the majority of the LATAM laboratories. Therefore, it is critical to reach potential sponsors to assist the LATAM molecular testing laboratories in overcoming these challenges and rapidly jump to the future. Efforts leading to improve tissue quality, to facilitate local optimization of assays and to ensure assay validation by international standards are needed. A group of regional laboratories have been trying to organize a collaborative project to face these issues and also to come up with an affordable strategy to ensure good quality in pathology and molecular laboratories. Multiple barriers are making it difficult to succeed in this effort. The patient advocate groups have proved effective in sensitizing governments and regulatory agencies in the USA, but those groups are still very under-represented in LATAM. Professional institutions such as the IASLC are specially tailored to help. IASLC congregates internationally conscious personnel and lung cancer experts and would excel, for instance, in matching experts with laboratories requesting specific assistance and in coordinating a regional consortium of laboratories interested in rounds of specimen exchange for proficiency testing and in validated sets of control specimens for implementation of new tests. Data from at least 15 of the highest populated LATAM countries regarding their lung cancer test menu, the technical platforms used, and efforts for investigation of the assay performance characteristics have been surveyed and results will be discussed. Precision Medicine Latin America