Meta-analysis shows lower prevalence of four known driver mutations among Black lung cancer patients. More research into tumor biology of Black patients might yield targeted therapies that would benefit Black lung cancer patients, says the lead author, Philippos A. Costa, M.D.
Oncology is well into the era of precision therapies that zero in on “driver mutations” that fuel cancerous growth and division especially nonsmall cell lung cancer (NSCLC). But a meta-analysis published in JCO Oncology Practice shows that Black lung cancer patients may be missing out when it comes to these targeted therapies because they are less likely to have the known driver mutations that the therapies target.
“We fear that the (limited) availability of those medications for this subset of population could even increase the gaps in outcomes among Black patients and other groups,” Philippos A. Costa, M.D., study’s lead author, said in a recent interview with MHE.
The meta-analysis by Costa and his colleagues comprised 20 studies and almost 12,000 patients. They used the data from those studies to compare the prevalence of EGFR, ALK, ROS-1 and BRAF mutations among Black lung cancer patients with the prevalence in their white, Hispanic and Asian counterparts.
Their results showed that the prevalence of those four known driver mutations was less among the Black lung cancer patients. For example, prevalence of EGFR mutations was 6% among Black lung cancer patients compared with 12% among White patients, 35% among Hispanic patients, and 46% among Asian patients. They found a similar pattern for the other three mutations.
Costa discussed ascertainment bias and some of the nuances of using race as a category for studies of genetic differences. Below are excerpts from that interview, edited for clarity and length.
Costa says encouraging more Black patients to enroll in clinical trials would be a first step to identifying driver mutations in Black patients that then might yield the identification of targeted therapies that would benefit Black patients. “For us to better understand the tumor biology of this group of patients, we need them enrolled into our clinical trials, so we can discover new driver mutations and new drugs that will benefit that population,” he said.
The study by Costa and his colleagues was published in the May issue of JCO Oncology. It was one of 16 articles and editorials on disparities in cancer care and outcomes for Black people in the U.S. in that issue of the journal.
For the last 15 years or so, there is this concept of driver mutations and targeted therapies, which drastically improve the survival in lung cancer.
For the patients to qualify for such treatments, they have to have what we call the driver mutations — EGFR mutations, ROS-1 mutations, BRAF mutations. And it is known that different races have different prevalences of those mutations. For example, white people have a prevalence of around 17% of EGFR mutations, while Asians have like a prevalence of 37% to 40%.
Because of the low inclusion of black patients in clinical trials, there was a question of what was the prevalence of those mutations in black patients? And the literature was not very clear on that. So that's what drove us to do this meta-analysis to try to figure out what was the prevalence of those driver mutations in black patients.
The incidence is quite interesting, because when the leading cause of lung cancer is smoking. Black and white people have the same incidence of smoking suggests that there could be like a different biology because (although) they smoke the same amount, black people have a tendency to have more lung cancer than their white counterparts.
Regarding the survival, when you look at the data, you'll see that Black patients have overall worse survival than white patients. But when you give them the same as access to care, you will see that those two groups have overall the same survival. So there is disparity in the care that these patients receive.
EGFR is the most common driver mutation that we looked at. The other ones are less prevalent. We saw that overall Black patients had fewer mutations (included in this study). But because of the low number of patients that had the other mutations that we had on our study we cannot say for sure that the prevalence that we found for the other mutations are representative of real-world data. So from the results of our study we will focus more on EGFR, because the number of patients that we were able to compare amongst different groups were higher, so the results that we had for EGFR were more signficiant.
Since they have fewer of the (known) driver mutations, they end up benefiting less from new medications. And since historically, they already had worse outcomes than the other groups of patients, we fear that the (limited) availability of those medications for this subset of population could even increase the gaps in outcomes among Black patients and other groups. So that's why we think it's very important to study the tumor biology of Black patients as this could potentially lead to discover of new driver mutations and new medications for those patients.
Historically, the Black population has been less enrolled in clinical trials than the white population. If you look at the U.S. census, around 13% of the population considers itself Black, and around 60%, white. And when you look at like some classical clinical trials, such as their lung cancer screening trial, you will see that 90% of the patients enrolled in that trial were white and a very, very small proportion were Black patients.
For us to better understand the tumor biology of this group of patients, we need them enrolled into our clinical trials, so we can discover new driver mutations and new drugs that will benefit that population.
Currently, NIH for its grants, requires that investigators enroll a certain number of Black patients, a certain number of white patients, (and a certain number of) Hispanic patients. This way, we can guarantee that we have a better representation of patients in the clinical trials, and then we can generalize the findings of those clinical trials to the general U.S. population.
We know that Asian people have more (known) driver mutations. We know that women in general have (a greater number of) driver mutations. And people that never smoked a higher number of driver mutations.
So let's suppose you're in a lower income country, and you don't have universal access to genetic testing. You'll see that an Asian woman that never smoked is more likely to be offered genetic testing in comparison (to another patients) that have a lower probability (of having a driver mutation). We think that this is not suitable strategy. If we pick and choose which patients are going to receive the genetic testing, we could increase the disparities of outcomes. So we favor universal genetic testing for all the (eligible) patients, according to the current (National Comprehensive Cancer Network [NCCN]) guidelines.
Testing was more expensive in the past. Every day it is getting more affordable, and since it is included in the current NCCN guidelines, usually insurance covers it and also Medicare or Medicaid. Each time that it gets more affordable, there is also this tendency for getting to universal testing — that also goes for other countries in the world that don't have the same purchasing power as the United States.
When you look at previous data, self reporting is able to give us an idea of [people’s] genetic background. So even if it's not perfect, it gives us a good idea. But how we are going to integrate that into our clinical practice — that is a very sensitive topic … But I completely agree that Black patients from the United States, Black patients from Ethiopia, Black patients from Brazil — they have different genetic backgrounds.