Subgroup Analysis of TAILORx Indicates Racial Disparity in Breast Cancer

Kathy Albain, MD

During a presentation at the 2018 San Antonio Breast Cancer Symposium, data from a subgroup analysis of the phase III TAILORx trial demonstrated worse outcomes in African-American patients compared to Caucasian patients with early breast cancer following adjuvant therapy. Both groups had a similar risk of recurrence and had received similar types of therapy, according the report.¹

Disease-free survival (iDFS), relapse-free interval (RFI), and overall survival were significantly worse in the African-American population, with a trend toward worse distant relapse-free interval (DRFI) as well. An analysis of the randomized component of the trial (endocrine vs chemoendocrine therapy, intermediate risk of recurrence) showed similar but larger disparities.

Across the study population, distribution of risk scores did not differ significantly between the 2 groups of patients, nor did the median or mean risk score. Data also indicated no significant differences in the type of adjuvant therapy received.

Results of the randomized component of TAILORx demonstrated noninferiority for adjuvant endocrine therapy versus chemoendocrine therapy, which applies to patients with hormone receptor (HR)—positive, HER2-negative, node-negative, early-stage breast cancer at an average risk of recurrence, Kathy Albain, MD, professor of hematology/oncology, of Loyola University Medical Center in Chicago, said during the meeting.

"The main message of this study—that chemotherapy in HR-positive/HER2-negative, node-negative breast cancer can be safely avoided in patients with a recurrence score less than 26—is true for all races and ethnicities analyzed," said Albain.

"Higher recurrence and overall mortality rates were observed for [African Americans] versus [Caucasians] and others. All the patients were enrolled in the same trial, treated identically with contemporary cancer care. The disparity is not explained by difference in recurrence score, reported endocrine therapy duration, use or type of adjuvant chemotherapy, or clinicopathologic factor."

The findings added to an existing body of evidence that a biologic basis, with or without other factors, may contribute to racial outcome disparities in HR-positive breast cancer, she added.

The findings came from the recently published TAILORx trial that compared adjuvant endocrine therapy with or without the addition of adjuvant chemotherapy in women with early-stage HR-positive/HER2-negative breast cancer, stratified by Oncotype DX Breast Recurrence Score Test.²

The trial included a total of 9719 evaluable patients. Patients with a low risk of recurrence (RS 0-10) received endocrine therapy, and those at high risk (RS 26-100) received endocrine therapy plus chemotherapy. Patients with intermediate-risk scores of 11-25 (N = 6711) were randomized to endocrine therapy alone or with chemotherapy. The trial met the primary endpoint, demonstrating noninferiority for endocrine therapy alone in the randomized, intermediate-risk group (HR, 1.08; 95% CI, 0.94-1.24).

Albain reported findings from an analysis to determine whether the lack of benefit with chemotherapy in the randomized patients applied equally to racial and ethnic subgroups. Investigators also wanted to determine whether race or ethnicity is an independent prognostic factor.

The analysis of outcomes and treatment effects by race and ethnicity was planned, but the trial lacked statistical power for evaluations of racial/ethnic subgroups, so no prospective statistical plan existed for interpretation subset comparisons, said Albain.

The TAILORx study population consisted of 8189 patients who identified as being Caucasian, 693 as African American, 405 as Asian, and 432 other/unknown. The Caucasian subset included 770 participants who identified as Hispanic.

As compared with Caucasian patients, African Americans were younger (age2 cm, 31% vs 24%), were more likely to have poor histologic grade (24% vs 17%), and had higher clinical risk (37% vs 29%). Hispanics were younger than non-Hispanics (

Risk score distributions, medians, and means did not differ significantly between African Americans and Caucasians or Hispanics and non-Hispanics. Type of chemotherapy, type of endocrine therapy, and duration of endocrine therapy also did not differ by race or ethnicity.

Overall, the addition of chemotherapy had no beneficial effect for any racial/ethnic group with respect to any of the endpoints assessed in the subset analysis.

Despite the lack of differences in factors that might influence clinical factors, African-American patients had worse outcomes at 9 years compared with Caucasians and other ethnic groups. The disparity occurred in the analysis of the randomized patients in iDFS (HR, 1.49;P= .001) DRFI (HR, 1.60;P= .02); RFI (HR, 1.80;P<.001) OS (HR, 1.67;P= .001) and in the overall population with iDFS (HR, 1.33;P= .005), DRFI (HR, 1.21;P= .28) RFI (HR, 1.39;P= .02) and OS (HR, 1.52;P= .005).

In a proportional hazards model, African Americans were associated with significantly worse outcomes as compared with Caucasians, independent other factors, in both the randomized and overall comparisons, said Albain.

The only exceptions to the impact of race on outcome occurred in the low-risk and high-risk subgroups. African-American patients with a low recurrence risk (RS 1-10) had iDFS and DRFI similar to other races. In the nonrandomized high-risk subgroup (RS 26-100) African Americans had results comparable to other races for all the outcomes.

References:

1. Albain K, Gray RJ, Sparano JA. Race, ethnicity and clinical outcomes in hormone receptor-positive, HER2-negative, node-negative breast cancer: results from the TAILORx trial. In: Proceedings from the 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas. Abstract GS4-07.
2. Sparano J, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer.N Eng J Med. 2018;379(2):111-121. doi: 10.1056/NEJMoa1804710.