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Women with early-stage breast cancer who are poorly represented in clinical trials have worse survival than their well-represented peers, according to a real-world analysis.
The study shows that more than half of women with early breast cancer are not well represented in clinical trials because of age, comorbidities, or race, yet they receive therapies based on the results of these trials.
“The most interesting finding is that patients with comorbidities resulting in lab abnormalities that would typically exclude them from receiving medication on a trial are still frequently receiving these medications and have an almost threefold higher mortality,” Gabrielle Rocque, naproxen og gravid MD, with the Division of Hematology and Oncology, University of Alabama at Birmingham, told Medscape Medical News.
“We need to do a deeper dive to better understand what is driving this mortality difference and test specific medications in patients with these conditions to understand the optimal treatment for this population,” Rocque added.
The study was published February 1 in JCO Oncology Practice.
Many patient groups are not well represented in clinical trials, including patients of color, older patients, and those with comorbidities, and it remains unclear how treatment outcomes may differ among these patients compared to those who are well represented in trials.
To investigate, Rocque and colleagues looked at 11,770 women diagnosed with stage I to III breast cancer between 2005 and 2015 in the American Society of Clinical Oncology (ASCO) CancerLinQ database.
White women between 45 and 69 years of age with no comorbid conditions were considered well represented and made up 48% of the cohort.
Non-White women and/or those younger than 45 years or older than 70 were considered underrepresented and made up 45% of the cohort. The unrepresented group (7%) included women with comorbidities — such as liver disease, renal insufficiency, thrombocytopenia, anemia, or uncontrolled diabetes — or concurrent cancer.
The majority of the women received a high-intensity chemotherapy regimen, including 58% of unrepresented, 66% of underrepresented, and 63% of well-represented patients.
Compared to well-represented women, unrepresented women had a higher risk of death at 5 years (adjusted hazard ratio [aHR], 2.71; 95% CI, 2.08 – 3.52).
Overall, the team found no significant increase in the risk of death at 5 years in underrepresented vs well-represented women (aHR, 1.19; 95% CI, 0.98 – 1.45). However, that risk varied with age. Among underrepresented women, those aged 70 and older had more than a twofold higher risk of 5-year mortality (aHR, 2.21), while those younger than 45 had a lower risk of 5-year mortality (aHR, 0.63), compared with those aged 45 to 69 years.
For three cancer subtypes, unrepresented patients had a greater than twofold higher risk of 5-year mortality compared to well-represented patients (aHR, 2.50 for HER2-positive disease; aHR, 2.54 for HR-positive/HER2-negative disease; and aHR, 2.75 for triple-negative disease).
Underrepresented patients with HR-positive/HER2-negative disease had a 38% increased risk of 5-year mortality compared to their well-represented peers (aHR, 1.38). However, there were no significant differences in 5-year mortality for underrepresented vs well-represented patients with HER2-positive or triple-negative subtypes.
Risky Business?
This analysis shows that unrepresented populations receive common treatment regimens at a similar rate as well-represented patients, the researchers note.
“By excluding patients with differing clinical conditions from trials but including them in the population to which drugs can be disseminated, one runs the risk of inadvertently causing injury,” the authors caution.
“To inform the practice of evidence-based medicine in an equitable manner, our findings support a need to both expand clinical trial inclusion criteria and report on clinical trial outcomes by clinical and demographic characteristics,” Rocque and colleagues conclude.
Charles Shapiro, MD, professor of medicine, hematology, and medical oncology, Icahn School of Medicine at Mount Sinai, in New York City, is not surprised by the findings of this study.
“We know that clinical trials are too restrictive and include only a selected population largely without comorbidities, but in the real world, people have comorbidities,” Shapiro, who was not involved in the research, told Medscape Medical News.
The study “starkly illustrates” the poorer survival of populations not represented in clinical trials.
“It could be that we need to change clinical trials, maybe ask fewer questions or maybe ask more important questions and loosen the eligibility up, because in the real world, there are people with comorbidities and people who are over 70,” Shapiro said.
Are strides being made to change that? “Not really,” Shapiro told Medscape Medical News.
The study was supported by grants from the Robert Wood Johnson Foundation and the American Cancer Society. Rocque has served as a consultant or advisor for Pfizer; has received research funding from Carevive Systems, Genentech and Pfizer; and has received travel, accommodations and expenses from Carevive. Shapiro has financial relationships with UptoDate, 2nd MD, and Anthenum.
JCO Oncol Pract. Published online September 24, 2022. Full text
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