Rising Tide of Biomarker Selected Studies – How Genomic Testing is Key to Unlocking Inequities in Oncology Clinical Trial Access

Overview

Dr. Hiba Khan led off her presentation by describing what biomarkers are and how they are used to guide targeted therapeutic approaches, predict the risk of recurrence or progression, and monitor for residual disease. She outlined how biomarkers are essential in applying precision medicine for disease prevention, diagnosis, and treatment while noting several studies have shown how biomarker testing inequities impact the ability of patients to enroll on clinical trials. Next, she reviewed a study that demonstrated how patients with stage IV lung cancer with a higher socioeconomic status received more genomic testing and how genomic testing was associated with improved overall survival in this patient population.¹ Dr. Khan reviewed another study which showed that patients with non-small cell lung cancer and colorectal cancer who had biomarker testing performed were more likely to enroll in clinical trials than patients who did not have biomarker testing.² The final study she reviewed was an analysis of patients enrolled in clinical trials that showed how American Indian and Alaska Native, Black, and Hispanic patients were under-represented in clinical trials after adjusting for various demographic factors.³

The importance of biomarker testing was further emphasized as Dr. Khan spoke about how cancer-related mortality rates among underrepresented minorities are higher, the incidence of targetable biomarkers differs by race and ethnicity, and biomarker testing rates are lower in patients who are not White as well as those with Medicaid and those residing in lower poverty tracts.^4–10 A Venn diagram showed how systems (payer coverage, standardization, workforce shortages), providers (guideline adherence, education gaps), and patients (distrust, time, social determinants of health) all play a role and are influenced by biomarker testing.^11–13 She emphasized improving access to biomarker testing and highlighted the ongoing GENTLeMEN and GIFTS studies created to enhance the feasibility of obtaining germline genetic testing and counseling.^14,15 Lastly, Dr. Khan stressed the importance of establishing community partnerships, addressing the social determinants of health, and engaging patient navigators to increase rates of biomarker testing.

Key Learnings

• Precision oncology can lead to improved outcomes, but inequities in access exist.

• Biomarker testing is essential to widening precision oncology clinical trial access.

Actionable Insights

• Identifying barriers to biomarker testing is key to designing interventions that move the needle toward equity.

Advanced Imaging and Stage Migration – How Findings More Diseases May Lead to More Opportunities

Overview

Dr. Curtiland Deville began his discussion by summarizing how prostate-specific membrane antigen (PSMA) PET-CT has ushered in a new era of detection in the staging of prostate cancer, detecting recurrence and metastatic progression, and monitoring response to radiopharmaceutical treatment. He discussed a trial of 307 patients with high-risk prostate cancer who underwent either PSMA PET-CT or conventional imaging that showed PSMA PET-CT had higher accuracy for staging nodal or distant metastatic disease while conventional imaging had more equivocal findings.¹⁶ Dr. Deville then spoke about a trial that included 208 patients with biochemically recurrent prostate cancer who underwent imaging with¹⁷F-DCFPyL that showed this imaging modality had a high disease detection rate and that using this imaging modality led to many patients having a change in management.¹⁸ A subsequent study showed that including the radiotracer¹⁷F-fluciclovine (Axumin), compared to conventional imaging, into salvage radiotherapy decision-making and planning improved three-year event-free survival.¹⁷ These studies culminated in the formulation of an ongoing trial that aims to identify the ideal strategy to treat patients who experience biochemical recurrence post-prostatectomy, named INDICATE (NCT04423211).

Dr. Deville then spoke about how the terms oligoprogression and oligometastatic disease are thought of in prostate cancer and how improving technologies to detect disease has led many to think of prostate cancer on a spectrum rather than solely localized versus metastatic disease. This led to a discussion of a trial of fifty-four patients with recurrent hormone-sensitive prostate cancer with one to three metastatic lesions that were less than or equal to five centimeters who underwent stereotactic ablative radiotherapy, which led to improvements in progression-free survival compared to patients who underwent observation.¹⁹ Dr. Deville posed the question as to whether radiopharmaceutical therapies, in conjunction with imaging techniques, could lead to better outcomes in patients with castrate sensitive disease and pointed to two trials evaluating this subject.^20,21

Then, Dr. Deville pivoted to tie in the aforementioned imaging techniques and how they could potentially exacerbate health disparities, as seen in a SEER analysis that showed Black male patients had higher odds of overuse of pelvic CT and bone scans, patients with higher income and younger age were more likely to receive imaging adherent to NCCN guidelines, and patients who were Black and Hispanic are less likely than White patients to receive prostate multiparametric MRI.²² Further, Dr. Deville touched on published data that suggested sociodemographic factors and manifestations of structural racism, including poverty and residential segregation, explained most of the racial disparity in the use of prostate MRI among Black versus White patients.²³ Similarly, at a single US tertiary medical center, access to ⁶⁸Ga-PSMA-11 for Black patients with prostate cancer was utilized nearly four times less than for White patients.²⁴ Next, Dr. Deville remarked on a review of twenty-two studies that showed variation in the type of therapies administered by insurance status, age, race/ethnicity, and location of residence (rural versus urban).²⁵ Lastly, Dr. Deville mentioned how Black patients with prostate cancer had been found to be less likely to receive shorter, accelerated (hypofractionated) radiation for prostate cancer and breast cancer despite evidence suggesting that shorter regimens may lower rates of noncompliance with similar oncologic outcomes.^26,27

Key Learnings

• Advanced molecular imaging has ushered in an improved era of diagnostic accuracy in prostate cancer.

• Radiopharmaceuticals are being deployed based on advanced molecular imaging in prostate cancer.

• Clinical outcomes after radiation therapy have improved based on prospective high-level evidence.

• Health disparities and inequities exist in the use of diagnostic imaging and radiation therapy for patients with prostate cancer.

Actionable Insights

• Future research will investigate how image-based risk stratification can better guide treatment and intensification strategies.

• Intentional efforts are needed to ensure that health inequities are not exacerbated by implementation gaps and provider bias in ordering advanced imaging technologies.

Applying a Social Determinant of Health Framework to Address Clinical Trial Inequities

Overview

Dr. Washington opened by defining healthcare disparities as differences between populations and groups and emphasized the importance of context in understanding how and why disparities exist. He reviewed the definitions of the term “social determinants of health” (SDoH) as made by the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO). The CDC adopted their definition of SDoH from the WHO, who define SDoH as the “conditions in which people are born, live, and age, and the wider set of forces and systems shaping the conditions of daily life”.²⁸ Dr. Washington reviewed the primary domains of the social determinants of health as outlined by the CDC’s Healthy People 2020 initiative: education access and quality, health care access and quality, neighborhood and built environment, social and community context, and economic stability. Next, he examined the discordance between the proportion of Black and Hispanic individuals living in the United States and the much lower proportion of Black and Hispanic patients enrolled in clinical trials.²⁹ He spent time differentiating SDoH from social risk and unmet social needs and explained how this distinction is vital in determining what is attributable to the environment, institutions, and structural racism. Finally, Dr. Washington illustrated how community-engaged approaches to advancing health equity improve patient outcomes. He clarified that healthcare providers and institutions must look into their own backyard to understand social risk factors before moving towards intervention.

Key Learnings

• More input from outside institutions and clinicians’ comfort zones is needed to guide research and improve cancer treatment and outcomes.

• The answers needed to push forward will come from partnerships outside the typical institutions and organizations.

• Community engagement requires interacting with the community to understand the community’s priorities.

Actionable Insights

• Develop strategic partnerships with community and local groups to understand local barriers to participation.

• Understand and assess SDOH-related issues that are most prevalent/impactful in the patient population.

• Identify local, institutional, and system-level resources to address and mitigate barriers.

Conflict of Interest

None

Funding information

N/A

Ethical statements

N/A

Acknowledgement

The authors thank the Binaytara Foundation for the opportunity to highlight this important topic.

Author contributions

i. All authors: conception and design

ii. All authors: data collection and assembly

iii. ML: data analysis, manuscript writing

All authors have approved the manuscript