BYLINE: Julie Grisham
In the last 25 years, almost 50% of the new cancer treatments authorized by the U.S. Food and Drug Administration (FDA) have been approved due to their effectiveness in targeting genetic alterations that contribute to tumor development.
Medical oncologists utilize data regarding genetic mutations present in tumors to align patients with targeted precision oncology therapies, many of which have now become standard components of care. Additionally, numerous precision oncology treatments are currently undergoing evaluation in clinical trials.
But unfortunately, not all patients have benefited equally from this molecular matchmaking. Patients of European ancestry are more likely to find a match to the latest treatments than patients of other ancestries, according to a new study from Memorial Sloan Kettering Cancer Center (MSK). The research was published January 9, 2025, in JAMA Oncology.
“Our findings are very concerning,” says MSK computational biologist Kanika Arora, MS, lead author of the paper. “Our research has found that especially in the past five years, when the largest number of precision oncology therapies have been approved, patients of African ancestry have been significantly less likely to benefit from these drugs compared with patients of European ancestry.”
“These findings highlight a trend that could be exacerbating the existing disparities in cancer outcomes that impact Black Americans and other minority populations,” adds MSK molecular geneticist Debyani Chakravarty, PhD, senior author of the new study.
(Note: The word “ancestry” pertains to an individual's genetic background and biological heritage, rather than the observable traits associated with their race or the cultural aspects linked to their ethnicity.)
Reasons Why Individuals of European Descent Have Access to More FDA-Approved Precision Oncology Cancer Treatments
In order to discover the DNA changes, or biomarkers, that predict how well a tumor will respond to a particular drug, scientists need data on DNA sequencing from large numbers of patient tumor samples. Historically, data from many academic medical centers, including MSK, have been pooled. These efforts include well-known projects such as The Cancer Genome Atlas (TCGA) and AACR Project GENIE.
“According to Dr. Chakravarty, more than 80% of the samples in these combined datasets come from self-identified white patients, mainly of European descent. This trend arises from the fact that these individuals have historically been the most likely, and often the most capable, of engaging in clinical trials. Consequently, the discovery of biomarkers and the following initiatives to create drugs tailored to specific molecular profiles are primarily founded on data derived from patients who predominantly possess European ancestry.”
In this research, the MSK team sought to determine if patients from various genetic backgrounds had an equal chance of being paired with an FDA-approved precision oncology medication, depending on the biomarkers present in their tumors. "Our findings revealed that this was not the case," explains Dr. Chakravarty.
The genetics of cancer and tumors varies according to a patient's ancestral background.
Scientists are learning that a person’s ancestry is linked to variations in their genes, including the genes that drive the formation and growth of cancer. Moreover, some cancer types are more common in people with certain ancestries.
How Scientists Discovered an Imbalance in the Availability of Targeted Cancer Therapies
To take a deeper look at the connections between ancestry and the precision oncology-based treatments available to patients, the JAMA Oncology study reviewed data from 59,433 patients who had their tumors analyzed with MSK-IMPACT® between January 2014 and December 2022. MSK-IMPACT looks for cancer-causing mutations in 505 cancer-associated genes. The patients’ names and other identifying information were removed to protect confidentiality.
The genetic material of every patient was examined to determine their "genetically inferred ancestry." Scientists focused on tiny genetic differences known as single nucleotide polymorphisms (SNPs, pronounced "snips"), which are inherited from parents and differ among various populations. By analyzing these differences, researchers calculated the percentage of genetic heritage from various ancestry groups, assigning patients to the group that made up at least 80% of their genetic composition.
The study found that approximately 75% of the patients undergoing MSK-IMPACT testing identified as having European ancestry, while lesser proportions were represented among those of East Asian, South Asian, and African ancestries.
The research did not include patients of mixed heritage, accounting for roughly 11% of the samples. A significant portion of these individuals identified themselves as Hispanic/Latino or Black/African American. This exclusion was due to the fact that these patients typically possess a combination of European, Indigenous, and/or African ancestry, with no one lineage being predominant.
The study looked at how likely patients were to be matched with FDA-approved precision oncology drugs over a 25-year period (1998–2023), during which a growing number of drugs received biomarker-based FDA approvals. The team used OncoKB, an MSK-developed, FDA-recognized database that contains hundreds of biomarkers for various cancer types, as well as information about the precision oncology drugs that match each of these biomarkers across different cancer types.
The study revealed that from 2012 to 2023, a period marked by the highest number of FDA drug approvals, the chances of being matched with an FDA-approved medication rose significantly. This trend persisted even when accounting for variations in cancer types, age, and gender.
During that timeframe, the likelihood of obtaining a personalized medication rose by roughly:
- 9.1-fold for patients of European ancestry
- 8.5-fold for patients of East Asian ancestry
- 6.8-fold for patients of South Asian ancestry
- 6-fold for patients of African ancestry
“In the initial stages of precision oncology treatment, there were minimal disparities between the various ancestry groups,” Arora explains. “However, with the increasing number of approved drugs, these differences have become more pronounced.”
Instances of Inequity in Access to New Cancer Medications Across Various Populations
There are numerous instances of particular categories of medications that can explain these variations.
When drugs targeting EGFR mutations in lung cancer became widely available, because patients of East and South Asian ancestries were more often eligible for the matched precision oncology drugs, because they were more likely to have those mutations.
Patients of European ancestry more often receive the immune checkpoint inhibitor drug pembrolizumab (Keytruda®). That’s because these patients are more likely than those of other ancestries to carry a molecular signature called high tumor mutation burden (TMB-H) in solid tumors.
More recently, several drugs have been approved to treat patients with lung and colorectal cancer with a particular tumor mutation called KRAS-G12C. But patients of African ancestry with colorectal cancer are more likely to have different KRAS mutations, against which the current FDA-approved drugs are much less, if at all, effective.
Addressing the Drug Disparity Gap: A Comprehensive Approach
Gaining insight into these genetic variations is one approach to bridging the disparity in cancer outcomes across individuals of various ancestral backgrounds.
Dr. Chakravarty states, "Cancer disparities arise from various factors, such as socioeconomic status and the resulting inequalities in healthcare access. To tackle these challenges, we must focus on improving access to clinical trials for patients with lower socioeconomic backgrounds. Additionally, it is crucial to gain insights from patients of diverse and underrepresented groups, similar to the knowledge we've historically acquired from patients of European descent, to inform the creation of new targeted therapies."
MSK has several efforts under way to increase clinical trial diversity, including partnerships with NYC Health + Hospitals, which reaches groups of people who have historically been less likely to participate in clinical trials.
This study received funding from the National Institutes of Health under grant number P30 CA008748.
