RxPONDER Reveals Worse Outcomes Shown in Black Women With HR+ Breast Cancer

Yara Abdou, MD

In the phase 3 RxPONDER trial (NCT01272037), worse outcomes were more likely in non-Hispanic Black patients with hormone receptor (HR)–positive/HER2-negative breast cancer vs non-Hispanic White, Asian, and Hispanic patients.¹

Results from the study were presented at a press conference during the 2022 San Antonio Breast Cancer Symposium. The poorer outcomes were observed even with similar 21-gene recurrence scores.

In RxPonder, investigators evaluated 4048 patients with HR-positive/HER2-negative breast cancer with 1 to 3 lymph nodes and a recurrence score of less than or equal to 25 whose race and ethnicity were known. Results showed that non-Hispanic Black patients were found to have a 5-year invasive disease-free survival (iDFS) rate of 87.2% vs 91.5% in non-Hispanic White patients (unadjusted HR, 1.39; 95% CI, 1.01-1.91; P = .04).

When conducting a multivariable analysis accounting for recurrence score, treatment arm, menopausal status, age, and grade, non-Hispanic Black patients had a 37% increased risk of invasive cancer than non-Hispanic whites, as well as lower distant relapse-free survival.

Of the race/ethnicities included on the trial, non-Hispanic Black patients had the worst overall iDFS outcomes while Asian patients had the highest (HR, 0.67; 95% CI, 0.45- 1.00; P = .05).

“Non-Hispanic Black woman with HR-positive/HER2-negative breast cancer, 1-3 positive lymph nodes, and recurrence score of less than or equal to 25, have worse outcomes compared with non-Hispanic White woman independent of recurrence score, treatment arm, age, and grade,” study author, Yara Abdou, MD, said in a presentation of the data. “[However], adjusting for body mass index [BMI] appears to decrease this effect.”

Abdou, a medical oncologist with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, reported on the RxPonder analysis during the 2022 SABCS.

The randomized phase 3 RxPONDER trial evaluated standard adjuvant endocrine therapy with or without chemotherapy in patients with HR-positive/HER2-negative breast cancer with 1 to 3 lymph nodes.

Investigators evaluated the 21-gene recurrence score, as well as the benefit of adjuvant chemotherapy in these patients, and for a recurrence score of less than or equal to 25. The genomic test measures tumor tissue to predict the risk of breast cancer recurrence, as well as the likelihood of responding to treatment.

Earlier data from the study showed that among premenopausal women with 1 to 3 positive lymph nodes, and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer iDFS and distant relapse–free survival (DRFS) than those who received endocrine-only therapy. Postmenopausal patients with similar characteristics did not benefit from adjuvant chemotherapy.²

In the 4048-patient trial, patients were non-Hispanic White (70%), non-Hispanic Black (6.1%), Hispanic (15.1%), Asian (8.0%), or Native American or Pacific Islanders (0.8%).

The median age of patients was 58 years old for non-Hispanic Whites, non-Hispanic Black patients, and Native American or Pacific Islander patients; the median age for Hispanic and Asian patients on the trial was 55 and 50 years, respectively.

Moreover, less non-Hispanic Black patients were pre-menopausal patients (23%) vs Asian patients (58%), for example. There were also no notable differences in tumor size, positive node status, or recurrence score distribution across all racial groups.

Further data showed that non-Hispanic Black patients had a DRFS rate of 90.1% vs 94.7% with non-Hispanic White patients (HR, 1.39; 95% CI, 1.01- 1.91; P = .004).

Investigators also evaluated acceptance of treatment assignments by race/ethnicity groups. Data showed that 93% of non-Hispanic Black patients accepted their treatment assignment vs 86% of non-Hispanic Whites accepting their treatment, demonstrating that treatment compliance is less likely attributable to differences in treatment outcomes.

Although recurrence scores were similar across all patient and racial subgroups, data showed that non-Hispanic Black patients had a higher likelihood of presenting with higher grade tumors (18%) vs non-Hispanic White patients (10%). Furthermore, non-Hispanic Black patients had the highest BMI scores across all subgroups.

“Black women have 4% lower incidence [rate], but a 40% higher breast cancer mortality than White women,” Abdou added.

The authors noted that a limitation of the study was the limited number of events that occurred in the non-Hispanic Black patient cohort, regardless of menopausal status. Longer follow-up and additional analyses are needed to confirm the findings.

_REFERENCES:

_{1. Abdou Y, Barlow WE, Gralow JR, et al. Race and clinical outcomes in the RxPONDER Trial (SWOG S1007): clinical trial Rx for positive node, endocrine responsive breast cancer. Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San San Antonio, TX. Abstract GS1-01.}

_{2. Kalinsky K, Barlow WE, Gralow JR. 21-gene assay to confirm chemotherapy benefit in node-positive breast cancer. N Eng J Med. 2021; 385(25):2336-2347. doi:10.1056/NEJMoa2108873}