Examining Equity Gaps in Immune Checkpoint Inhibitor Trials for NSCLC

In this interview, Adam A. Barsouk, MD, discusses his study, “Disparities in Non-Small Cell Lung Cancer (NSCLC) by Age, Sex, and Race: A Systematic Review and Meta-Analysis of Immune Checkpoint Inhibitor (ICI) Trials.” Dr Barsouk explores persistent gaps in representation within immunotherapy trials, the risks these disparities pose to evidence-based care, and the steps needed to ensure more equitable evaluation and access for historically underrepresented patient populations.

Key Takeaways:

• Persistent underrepresentation of women, older adults, and Black patients in NSCLC immune checkpoint inhibitor trials limits the generalizability of evidence used to guide clinical decision-making.
• Disparities in trial enrollment may mask clinically meaningful differences in immunotherapy response and survival across age, sex, and racial groups.
• Improving equitable trial access, community engagement, and diversity among clinical investigators is essential to ensure NSCLC treatment guidelines reflect real-world patient populations.

Adam Barsuk, MD: My name is Adam Barsuk. I am a resident physician at the Hospital of the University of Pennsylvania and an incoming oncology fellow at Johns Hopkins University. I have been conducting clinical cancer research for nearly 10 years now. I was privileged to get to work with my colleagues here at the University of Pennsylvania to put forth this meta-analysis of immunotherapy trials and disparities in survival.

Can you give some background about your study and what prompted you to undertake it?

Dr Barsouk: I have been working in clinical cancer research for over 10 years now. We have been utilizing these large databases that are only now becoming available to researchers to evaluate trends in survival and cancer disparities, and possible preventative strategies. We saw an unmet need in looking at what patient populations have been included in immunotherapy trials and NSCLC, as well as any survival disparities that still persist into the modern day.

Given the persistent underrepresentation of women, older adults, and Black patients in phase 3 ICI trials, what are the risks of relying on current evidence to inform standardized clinical pathways in NSCLC?

Dr Barsouk: There are significant risks. As you mentioned, some of these populations are fairly poorly represented. Black patients make up less than 2% of all the clinical trial patients, although they make up around 15% of the US population and a greater percentage of all lung cancer diagnoses. So, we are failing our patients in representing them in the trials off which we base our clinical decision-making. That is important because sometimes there are disparate outcomes. In a separate study in bladder cancer, we found that women respond poorer to immunotherapy and have poorer survival than male patients. That would not have been evident had women not been included in the trials sufficiently.

Many of the Asian patients in your meta-analysis were enrolled in trials that intentionally focused on predominantly Asian populations to explore potential racial differences in ICI response. What lessons can trial designers take from this approach when thinking about how to meaningfully increase enrollment of Black and other underrepresented populations?

Dr Barsouk: It's important to note that it's not always clear in these trials what proportion of the Asian patients are Asian American vs enrollees from other East Asian nations. The clinical trial infrastructure is not quite as built up for this disctinction. You don't have the same health system infrastructure in many African countries, for example. And moreover, it's not clear that you could extrapolate the data that you get from patients in Africa to the African American population, which has very distinct social and cultural factors that influence outcomes.

The best strategy is to improve enrollment here in the US and to provide more access to clinical trials for diverse patients—Black patients, Hispanic patients, Asian American patients—in order to have better representative data.

Based on your findings, what concrete changes in trial design, enrollment strategies, or policy initiatives are most urgently needed to ensure equitable evaluation of ICIs and to better inform clinicians treating underrepresented populations?

Dr Barsouk: First and foremost, we need to restore public funding to the National Institutes of Health and the clinical research infrastructure. Second, historically, we have failed to sufficiently enroll certain populations, particularly African Americans, in many of these trials. It's important to continue outreach at academic centers that are in heavily Black communities such as the University of Pennsylvania and Johns Hopkins University.

It's equally as important to have more representation of Black Americans in leading roles in medicine in these trials because studies show that people trust others who look like them, act like them, and sound like them. There have been many successful initiatives to increase enrollment. Sometimes it takes thinking outside of the box. For example, I saw an initiative where public health information was dispensed by barbers in the Black community, which helped to increase adherence with anti-hypertensive regimens.

So, we have to engage these communities and the people who are leaders in these communities, and make sure to have equal representation, not just in our trials, but in medicine and policy in our health system overall.

Is there anything else you hope audiences will take away from this study?

Dr Barsouk: I think we are seeing growing disparities in survival by race in the US as well as growing cancer incidents, particularly among young adults. And these are concerning trends that we ought to be researching more and addressing.