FDA Analysis of Enrollment of Pediatric and AYA Patients in Clinical Trials By Race and Ethnicity

Introduction: Cancer is the leading cause of death from illness in the pediatric population in the United States (US). However, tremendous progress has been made in the treatment of pediatric cancer and over 80% of pediatric patients diagnosed with cancer will be long-term survivors. Earlier studies have shown the racial and ethnic background of pediatric patients enrolled in cancer clinical trials to be comparable to the racial distribution of pediatric cancer in the US, but recently there has been a decline in representation of underrepresented populations in pediatric clinical trials. This is of particular concern due to the possible genetic or metabolic differences in patients from different racial and ethnic groups that may affect response to novel therapies and survival rates. In this study, we analyzed the racial and ethnic enrollment in pivotal clinical trials that led to drug approval for malignant hematological diseases in the pediatric and adolescent/young adult (AYA) populations.

Methods: Demographic data was collected from registrational trials submitted to the FDA from 2012 to 2023 to support the approval of drugs in the pediatric and AYA populations for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Only patients that were enrolled and treated were included in the analysis. The distribution of race (White, Black, Asian/Pacific Islander [API], American Indian/Alaska Native [AIAN]) and ethnicity (Hispanic, non-Hispanic) for patients enrolled on trials were compared to the corresponding distribution of US ALL, AML, and CML incident cases in pediatric and AYA patients (<30 years) obtained from the North American Association of Central Cancer Registries (NAACCR) for the years 2012-2021.

Results: A total of 14 pivotal trials enrolling 2,218 pediatric and AYA patients from ages 0-29 years were included in the analysis. This included 8 trials in ALL (N=846), 4 trials in CML (N=306), and 2 trials in AML (N=1066). Regarding the racial composition of the pivotal trials overall and by disease: ALL, AML and CML, 72% (71.6, 73.4, and 68%) (N=1596) of patients identified as White, 8.3% (6.1, 11.0, and 4.9%) (N=184) identified as Black, 6.8% (3.9, 5.0, and 20.9%) (N=150) identified as API, 2% (0.6, 3.4, and 1.0%) (N=44) identified as AIAN, 5.5% (7.7, 4.9, and 1.6%) (N=122) listed their race as “other”, 5.2% (9.8, 2.1, and 3.3%) (N=118) did not have their race provided or was unknown, and 0.3% (0.8, 0.4, and 3.3%) (N=6) identified as more than one race, respectively. There were 385 patients (17.4%) (20.3, 17.5, and 8.5% respectively) who identified as having Hispanic ethnicity.

According to NAACCR data the racial distribution of leukemia cases overall and by disease (ALL, AML, CML) were as follows: 78% (80.8, 73.7 and 71.7%) White; 10.6% (8, 14.8 and 16.1%) Black; 6.3% (5.8, 7.1 and 6.5%) API; and 1% (1, 0.9 and 0.9%) AIAN, respectively. Hispanic ethnicity accounted for 31.5% (35.6, 25.0, 23.1 %) of the pediatric and AYA patient population, respectively.

Comparing distribution of race and ethnicity in trial data to NAACCR, there was a low enrollment of Black and Hispanic across pivotal clinical trials that led to drug approvals for leukemia in the pediatric and AYA populations.

Conclusions: Our results demonstrate underrepresentation of Black and Hispanic pediatric and AYA patients in leukemia clinical trials. The difference in proportions of minorities between the clinical trials and NAACCR data may be associated with biological or socioeconomic factors that are outside the scope of this analysis. The limitations of the report are that it only analyzed patients enrolled and treated in pivotal trials and did not include patients that were in earlier phase/supportive trials or patients that were screened and deemed to be ineligible for the studies. Nevertheless, the FDA remains committed to collaboration with investigators and pharmaceutical companies to find innovative solutions to increase enrollment of underrepresented minorities in cancer clinical trials.