Clinical trial representativeness and treatment intensity in a real-world sample of women with early-stage breast cancer.

Abstract

6584 Background: Early stage breast cancer (EBC) treatment is used in women of all ages, races, and health states. However, as clinical trials often do not represent real-world populations, the extent to which evidence-based treatments are prescribed to populations not well represented in these trials is not known. This study evaluated treatment intensity for patients traditionally well represented, underrepresented, and unrepresented in clinical trials. Methods: This retrospective cohort study used the nationwide de-identified electronic health record derived Flatiron Health database for patients diagnosed with EBC between 2011-2020. We categorized treatments as either high- (AC-TH [doxorubicin, cyclophosphamide followed by paclitaxel or docetaxel, trastuzumab]; ACT [paclitaxel or docetaxel, doxorubicin, cyclophosphamide]; TCH [paclitaxel or docetaxel, carboplatin, trastuzumab]; TCHP [paclitaxel or docetaxel, carboplatin, trastuzumab, pertuzumab]) or low-intensity (AC [doxorubicin, cyclophosphamide]; TC [paclitaxel or docetaxel, cyclophosphamide]; TH [paclitaxel or docetaxel, trastuzumab]). Unrepresented patients often have one or more comorbidities and/or prior cancer; underrepresented patients are typically Black, Indigenous, people of color, or of age extremes ( < 45, 70+); well represented patients are White and between the ages of 45-69. Odds ratios (OR), predicted proportions, and 95% confidence intervals (CI) from a two-level (patients nested in practice) hierarchical logistic regression model evaluated associations between receipt of high-intensity chemotherapy and patient characteristics of clinical trial representation (age, race/ethnicity, presence of comorbidity). Results: Our study included 970 patients with EBC with 13%, 45%, and 41% characterized as unrepresented, underrepresented, and well represented in clinical trials, respectively. In the adjusted model, those aged ≥ 70 vs 45-69 had lower odds of receiving a high-intensity treatment (OR 0.40, 95% CI 0.26-0.60), while those aged < 45 vs 45-69 had higher odds of receiving high-intensity treatment (OR 1.82, 95% CI 1.10-3.01). The predicted proportion of patients receiving a high-intensity treatment was 87% (95% CI: 80%-92%) for patients aged < 45, 79% (95% CI: 74%-84%) for patients aged 45-69, and 60% (95% CI: 50%-70%) for patients aged ≥ 70. Neither race/ethnicity nor comorbidity status were associated with odds of receiving high-intensity chemotherapy. Conclusions: Over half of the EBC population is not well represented in clinical trials. Age was associated with differential treatment intensity, despite a lack of evidence that these differences are appropriate. Widening clinical trial eligibility criteria is one way to better understand survival outcomes, identify potential toxicities, and ultimately make evidence-based treatment decisions using a more diverse sample.