Addressing Cancer Health Disparities in Latinos via Clinical Trials

Jorge Gomez
Center for Genomic and Precision Medicine, Texas A&M University

ealth disparity is defined as the unequal burden of disease in a population due to race, ethnicity, gender, education, socioeconomic status, disability, geographic location, sexual orientation, or cultural or religious beliefs. In this article, the term Latino includes individuals that migrated from Mexico, Central, and South America, and from Latino members of the Caribbean population. These individuals have a diverse racial makeup and heterogenous genetic ancestry that must be considered when studying Latino populations at various levels including clinical trial outcomes.

Several outstanding analyses and presentations in various formats outlined the need to integrate Latinos in a variety of research areas instead of aggregating them and treating them as a single and separate/distinct group. The purpose of this article is to emphasize the importance of including Latinos in US national clinical trials and the funding agencies’ responsibility for their inclusion.

Effective Precision Medicine Strategies Depend upon the Population Studied

In the era of precision medicine, it is imperative that we measure the molecular target taking into consideration the population as a whole, as well as the disaggregated subgroups. These include the major groups that represent the whole US population: whites of European descent, African Americans, Latinos, and Asians. It is also worth mentioning that all these groups are internally heterogeneous and there might be biological differences within each group. Any approved drug that reaches the general population is the result of sizable and laborious work from in vitro tests, animal models, and several iterations of clinical trials that end up benefiting the population at large.

Clinical research outcomes fall into well-defined categories: a) no benefit and no toxicity, b) no benefit and toxicity, c) benefit and toxicity, and d) benefit and no toxicity. Regulatory approval is usually based on c) and d), and these groups usually are the larger percentage that present benefit outcomes. The above categories are applicable to all ethnic and racial groups, with some variations among them within each group. Responses to treatment (as well as diagnoses) are the result of the genetic and epigenetic composition of ethnic and racial groups and their intrinsic variability. These responses to treatment are the result of various degrees of genetic modifications of drug-metabolizing enzymes that affect how drugs are processed (via oxidation, hydroxylation, reduction, or hydrolysis, among other reactions) and excreted from the body.

Disparate Populations Often Have Distinctive Mutant Alleles

Several mutant alleles have been identified and shown to be distinct among specific ethnic and racial groups, thus justifying the inclusion of all ethnic groups in all types of clinical trials. Expression of epidermal growth factor and BCR-ABL1 receptors, KRAS, HER2, and many others affect treatment modalities that must be taken into consideration. The above categories have been identified mostly by studying the “nonresponders” with or without toxic effects. Triple-negative breast cancer was identified in a subgroup of African Americans (AA) after it was noticed that a substantial number of AA did not respond to tamoxifen, a standard treatment at the time. Perhaps this would have been unnecessary if AA women had been appropriately represented in the large tamoxifen clinical trials. These large groups—AA, Latinos, and Asians—are grossly underrepresented in the large confirmatory phase 3 clinical trials. These include population-based, biomarker, and various therapeutic modality clinical trials.

Government-Sponsored Trials Need to Be More Proactive in Enforcing Their Policies

Although the US Congress has made it clear that government-sponsored clinical trials must include all sectors of the US population, government agencies such as the FDA continue to accept low numbers of AA, Latinos, and other underrepresented groups in clinical trials. The number of AA in clinical trials has increased in the last several years, but the number of Latinos remains extremely low at approximately 5%. It is the responsibility of the various federal government agencies (listed below) that have jurisdiction over clinical research to review the annual progress reports and deem these studies unacceptable if the grantees and contractors fail to include appropriate representation of Latinos and other subpopulations in clinical trials. Waiting for the trial to end and discovering that representation is inadequate is both late and wasteful. US federal agencies responsible for the administration of federal funding in this area include the Food and Drug Administration (FDA), National Institutes of Health (NIH, including the National Cancer Institute [NCI]), Centers for Disease Control and Prevention (CDC), and Department of Defense (DOD). Most of these agencies rely on the peer-review system, which affords many opportunities to revise plans, feasibility, and intent to include Latinos and other subpopulations in clinical trials. The second level of review is at the implementation stage, monitored through annual reports once a grant or contract has been funded. Continuing to fund clinical research without appropriate accountability is unacceptable from scientific, moral, and political points of view. The technological advances of the last two decades and the scientific information now available make this task easier than it was in the last century when there was very little scientific information regarding, for example, cancer in Latinos.

Meetings and Outreach to Advance the Science of Cancer in Latinos

Researchers from all areas of cancer research have been gathering in an academic setting to present and discuss findings and research advances under the forum Advancing the Science of Cancer in Latinos in San Antonio (Texas, US) every other year, by far the most comprehensive forum to discuss advances and the science of cancer in Latinos in the US and worldwide. To this end, academic institutions that have been granted the privilege of conducting clinical trials also bear the responsibility of being inclusive of all populations, including Latinos, in the design and implementation of clinical research. The old “catchment area” and “work with whatever is available around my area” are no longer acceptable. Academic institutions have an obligation to include all sectors of the population in their research studies, and government agencies should be ready to incentivize and reward their efforts.

Regional and community hospitals can prove to be a substantial resource for patients, particularly for trials that might be less technologically challenging. Patients stand to benefit the most if the reach of science touches those that have been almost forgotten by the modern world. These patients will adhere to a clinical trial if they participate at the local level along with their physicians. Physicians from these local community hospitals are favorable to these trials and are familiar with the issues of their patient populations. For them, issues of acculturation, diet, comorbidity, and other factors that are studied in an academic setting are the bread and butter of everyday life; they practice medicine by addressing cancer health disparities every day. In addition, efforts to include Latin American countries in US-initiated clinical trials have merit, as the inhabitants of these countries have the same characteristics as the US Latino population. The success of US clinical research, including clinical trials, will increasingly be defined by the appropriate representation of all US subpopulations, thus preventing the need for rework due to inadequate representation that is discovered after the studies are completed.

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