Klaassen, Zachary

Background Ensuring representative data accrual in clinical trials is important to safeguard the generalizability of results and to minimize disparities in care. This study's goal was to evaluate differences in gender representation in trials leading to US Food and Drug Administration (FDA) cancer drug approvals. Methods An observational study was conducted from January 2014 to April 2019 using PubMed and the National Institutes of Health trials registry for primary trial reports. The National Cancer Institute's Surveillance, Epidemiology, and End Results program and US Census were consulted for national cancer incidence. The outcome was an enrollment incidence disparity (EID), which was calculated as the difference between male and female trial enrollment and national incidence, with positive values representing male overrepresentation. Results There were 149 clinical trials with 59,988 participants—60.3% and 39.7% were male and female, respectively—leading to 127 oncology drug approvals. The US incidence rates were 55.4% for men versus 44.6% for women. Gender representation varied by specific tumor type. Most notably, women were underrepresented in thyroid cancer (EID, +27.4%), whereas men were underrepresented in soft tissue cancer (EID, –26.1%). Overall, women were underrepresented when compared with expected incidence (EID, +4.9%; 42% of trials). Conclusions For many specific tumor types, women are underrepresented in clinical trials leading to FDA oncology drug approvals. It is critical to better align clinical trial cohort demographics and the populations to which these data will be extrapolated. Lay Summary This study assesses whether gender disparities exist in clinical trials leading to US Food and Drug Administration (FDA) cancer drug approvals. From January 2014 to April 2019, 149 clinical trials leading to FDA oncology drug approvals showed 60.3% and 39.7% of the enrollees were male and female, respectively. Gender representation varied by specific tumor when compared with the expected incidence rate of cancer in the United States, although women were more often underrepresented. Increased efforts are needed with regard to ensuring equitable representation in oncology clinical trials.

Objectives: Immunotherapy (IO) has become standard of care (SOC) for many advanced malignancies, although identifying patients likely to benefit remains difficult. We sought to assess whether demographic factors are associated with response to IO, compared with SOC systemic therapy, using stratified meta-analysis. Methods: A systematic review of MEDLINE, PubMed, Embase, and Scopus from inception to October 2, 2018. Randomized controlled trials comparing IO to SOC in patients with advanced solid organ malignancies were included if results were stratified by age, performance status (PS), or race, assessing overall survival (OS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for each group using random-effects models independently. Results: We identified 21 eligible randomized controlled trials, including 20 stratified by age, 17 by PS, and 4 by race. Patients with PS 0 (HR, 0.74; 95% CI, 0.63-0.86) and PS≥1 (HR, 0.75; 95% CI, 0.68-0.83) had similar OS benefits from IO compared with SOC (P=0.80). There was no difference on the basis of patient race (white vs. nonwhite) (P=0.46). IO demonstrated an OS benefit for younger (below 65 y: HR, 0.73; 95% CI, 0.65-0.82) and older (65 y and above: HR, 0.79; 95% CI, 0.71-0.88) patients with no difference between age groups (P=0.27). Among prespecified subgroup analyses, there was significant effect modification in 2 subgroups: younger patients in the first-line setting (P=0.03) and those receiving anti-CTLA-4 drugs (P=0.05). Conclusions: When examining OS using stratified meta-analysis, we did not demonstrate significant differences in IO efficacy according to patient age, PS or race, though data on race were sparse.