OBJECTIVES: In randomized clinical trials (RCTs) for oncology, individuals assigned female at birth have historically been underrepresented. However, the significance of this variance and extent to which it impacts the representativeness of cancer research data sets have not been established. We evaluated 5 recently completed real-world (RWE) studies, corresponding RCTs, and SEER data from a parallel time period to assess female sex representation.

METHODS: Sex at birth for patients with advanced lung, liver, melanoma, or kidney cancers (2) was compared across 5 RWE chart review studies (completed between 2020-2022), 5 corresponding RCTs (reported between 2014-2021), and the most recently available SEER data for the diagnoses (2017-2019) using 2-sided chi-square tests.

RESULTS: Sex at birth was collected for 26,325 patients (RWE: n=2,120, 8.1%; RCT: n=3,962, 15.1%; SEER: n=20,243, 76.9%). Aggregated across the populations studied, female representation was 37.6% in RWE, 26.4% in RCTs, and 29.6% in SEER. Female representation was significantly higher in RWE than RCT (P<.001) and in RWE than SEER (P<.001). Within advanced renal cell carcinoma, female representation was significantly higher in RWE (36.4%) compared with RCT (26.6%, P<.001) and SEER (29.2%, P=.006). Female representation was also significantly higher in advanced non-small cell lung cancer RWE studies (40.5%) than in RCTs (18.6%, P<.001) and in advanced melanoma RWE studies (44.9%) than in RCTs (35.4%, P=.001).

CONCLUSIONS: Participants assigned female at birth remain underrepresented in RCTs, which drive inferences about the safety and efficacy of interventions, clinical decision-making, and payer reimbursement. Despite limitations including different study periods and unique sex distributions associated with some cancer types, female representation was highest in RWE studies and lowest in RCTs. Well-conducted RWE studies may fill gaps left by RCTs for improving representation and generalizability to female patients with cancer.