Dr. Debyani Chakravarty studies how the genetic changes found in tumors can be used to match patients with precision oncology treatments.
Nearly half of all new cancer drugs approved by the U.S. Food and Drug Administration (FDA) over the past quarter-century have received that approval based on their ability to target genetic changes driving tumor growth.
Medical oncologists use information about the genetic mutations found in tumors to match patients with specific precision oncology therapies — many of which have become part of standard treatment. Many more precision oncology treatments are being tested 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 term “ancestry” refers to a person’s genetic origin and biology, as opposed to the physical characteristics of their race or the cultural identification of their ethnicity.)
Why People of European Ancestry Have More FDA-Approved Precision Oncology-Based Cancer Treatment Options
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.
“Over 80% of the samples included in these pooled datasets are from self-reported white patients, predominantly of European ancestry, because these are the patients who historically have been most likely, and often most able, to participate in clinical trials,” Dr. Chakravarty says. “This means that biomarker discovery and subsequent efforts to develop molecularly matched drugs are based on data from patients who are overwhelmingly of European ancestry.”
In this study, the MSK team decided to ask whether patients across all genetic ancestries had the same likelihood of being matched with an FDA-approved precision oncology drug based on the biomarkers found in their tumors. “We found the answer to be ‘no,’” Dr. Chakravarty says.
Cancer and Tumor Genetics Differs Based on a Patient’s Ancestry
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.
For example:
- People of African ancestry are more likely to develop multiple myeloma, prostate cancer, triple-negative breast cancer, and uterine (endometrial) cancer.
- People of East Asian ancestry have higher rates of stomach (gastric) cancer and certain head and neck cancers.
How Researchers Uncovered a Disparity in the Targeted Cancer Drugs Available
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 DNA of each patient was analyzed to establish “genetically inferred ancestry.” Researchers looked for small genetic variations called single nucleotide polymorphisms (SNPs, pronounced “snips”), which are passed down from parents and vary across populations. Based on these variations, the proportion of genetic background from different ancestry groups was calculated, and patients were assigned to the group that comprised at least 80% of their genetic makeup.
The researchers determined that about three-quarters of the patients who had received MSK-IMPACT testing were of European ancestry, compared with smaller percentages who had East Asian, South Asian, and African ancestry.
The study excluded patients with mixed ancestry — about 11% of the samples — many of whom self-reported as Hispanic/Latino, or Black/African American. That’s because these individuals often have a blend of European, Indigenous, and/or African ancestry, and no single ancestry is dominant.
The Dramatic Gap in Treatments Over Time Between Ancestry Groups
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 researchers found that between 2012 and 2023, when the largest number of drugs received FDA approval, the likelihood of getting matched with an FDA-approved drug increased by varying degrees. This was true even after factoring in differences in cancer type, age, and sex.
In that time period, the odds of receiving a personalized drug increased approximately:
- 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 early years of precision oncology therapy, there were no significant differences among the ancestry groups,” Arora says. “But as more drugs have received approval, the differences have grown wider.”
Examples of the Disparity in New Cancer Drugs Available to Different Populations
There are several examples of specific types of drugs that can help account for these differences.
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.
The Solution to Closing the Drug Disparity Gap
Understanding these kinds of genetic differences is one solution to closing the gap in cancer outcomes among people of different ancestries.
“We know there are many reasons for cancer disparities, including differences in socioeconomic status and associated disparities in access to care,” Dr. Chakravarty says. “One way we can begin to address these issues is to understand and facilitate access to clinical trials for patients of lower socioeconomic status. We also need to learn from patients from diverse and underrepresented backgrounds, just as we have learned historically from patients of European ancestry, to guide the development of newer targeted drugs.”
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.
