In a retrospective cohort study reported in JCO Oncology Practice, Gidwani et al found that among U.S. patients treated for early-stage breast cancer, those who were considered to be unrepresented in clinical trials have significantly poorer survival than those categorized as well represented. Among those considered underrepresented, survival differed according to age.
Study Details
The study included data on 11,770 women diagnosed with stage I to III breast cancer between 2005 and 2015 from the national CancerLinQ Discovery electronic medical record–based data set. Patients were categorized as unrepresented, underrepresented, or well represented in clinical trials based on review of clinical trial protocols and published literature on trial-based patient demographics. Patients considered unrepresented had concurrent cancer or a comorbidity commonly associated with exclusion from trial eligibility as reported on ClinicalTrials.gov using the I-SPY laboratory criteria. Patients considered underrepresented were Black, Indigenous, or people of color, as well as those younger than age 45 or age 70 and older. Patients considered well represented were White, aged 45 to 69 years, and had no exclusionary comorbidities or concurrent cancers. Cox proportional hazards models were used to evaluate 5-year mortality, with adjustments for cancer stage, subtype, chemotherapy, and year of diagnosis.
Key Findings
Among the 11,770 patients, 48% were considered well represented in clinical trials, 45% were considered underrepresented, and 7% were considered unrepresented.
More than half of the patients were under-represented or unrepresented in clinical trials, because of age, comorbidity, or race. Some of these groups experienced poorer survival compared with those well-represented in trials. Trialists should ensure that study participants reflect the disease population to support evidence-based decision-making for all individuals with cancer.— Gidwani et al
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Overall survival at 5 years postdiagnosis was estimated at 90% (95% confidence interval [CI] = 88%–92%) for unrepresented patients, 95% (95% CI = 94%–96%) for underrepresented patients, and 96% (95% CI = 95%–97%) for well-represented patients. In adjusted analysis, compared with well-represented patients, survival was significantly poorer among unrepresented patients (adjusted hazard ratio [HR] = 2.71, 95% CI = 2.08–3.52) but not among underrepresented patients (adjusted HR = 1.19, 95% CI = 0.98–1.45).
Among underrepresented patients, those younger than age 45 had reduced 5-year mortality (adjusted HR = 0.63, 95% CI = 0.48–0.84) and those age 70 or older had increased mortality (adjusted HR = 2.21, 95% CI = 1.76–2.77) vs those aged 45 to 69.
Analysis by cancer subtype showed greater risk of 5-year mortality in unrepresented vs well-represented patients for HER2-positive/any–hormone receptor (HR) status disease (adjusted HR = 2.50, 95% CI = 1.39–4.48), HR-positive/HER2-negative disease (adjusted HR = 2.54, 95% CI = 1.75–3.68), and HR-negative/HER2-negative disease (adjusted HR = 2.75, 95% CI = 1.68–4.50). Compared with well-represented patients, underrepresented patients with HR-positive/HER2-negative disease had an increased risk of 5-year mortality (adjusted HR = 1.38, 95% CI = 1.06–1.78), with no significant differences observed for other subtypes.
The investigators concluded, “More than half of the patients were under-represented or unrepresented in clinical trials, because of age, comorbidity, or race. Some of these groups experienced poorer survival compared with those well-represented in trials. Trialists should ensure that study participants reflect the disease population to support evidence-based decision-making for all individuals with cancer.”
Gabrielle B. Rocque, MD, of the University of Alabama at Birmingham, O’Neal Comprehensive Cancer Center, is the corresponding author for the JCO Oncology Practice article.
Disclosure: The study was supported by the Robert Wood Johnson Foundation and an American Cancer Society Mentored Research Scholar grant. For full disclosures of the study authors, visit ascopubs.org.
