In an interim analysis of the phase III RxPONDER trial reported in The New England Journal of Medicine, Kevin Kalinsky, MD, and colleagues found that the addition of adjuvant chemotherapy to endocrine therapy did not improve invasive disease–free survival among women with hormone receptor–positive, HER2-negative, node-positive breast cancer and a 21-gene assay recurrence score of 25 or less; no association of chemotherapy benefit with increasing recurrence score was observed. Significant benefit of chemoendocrine therapy was observed in premenopausal—but not postmenopausal—women.

The investigators stated, “The recurrence score based on the 21-gene breast cancer assay has been clinically useful in predicting a chemotherapy benefit in [hormone receptor–]positive, HER2-negative axillary lymph node–negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear.”

Kevin Kalinsky, MD

Study Details

In the open-label trial, 5,018 eligible women with one to three positive axillary lymph nodes and a recurrence score of ≤ 25 were randomly assigned between February 2011 and September 2017 to receive chemoendocrine therapy (n = 2,511) or endocrine therapy alone (n = 2,507). Patients had to be eligible for a chemotherapy regimen containing a taxane, an anthracycline, or both. The primary objective was to determine the effect of chemotherapy on invasive disease–free survival and whether the effect was influenced by recurrence score. Overall, 33% of patients in both groups were premenopausal and 67% were postmenopausal.

Invasive Disease–Free Survival

At the prespecified third interim analysis, median follow-up was 5.3 years. Among all patients, invasive disease–free survival at 5 years was 92.2% in the chemoendocrine therapy group vs 91.0% in the endocrine therapy group (P = .10). No significant interaction was found between chemotherapy benefit and recurrence score categories of 0 to 13 and 14 to 25 (P = .89).

The effect of chemotherapy on invasive disease–free survival differed significantly according to menopausal status (P = .008). Invasive disease–free survival at 5 years was 91.3% in the chemoendocrine therapy group vs 91.9% in the endocrine therapy group (hazard ratio [HR] = 1.02, 95% confidence interval [CI] = 0.82–1.26, P = .89) among postmenopausal women and 93.9% vs 89.0% (HR = 0.60, 95% CI = 0.43–0.83, P = .002) among premenopausal women.

For the chemoendocrine therapy group vs endocrine therapy group, distant relapse–free survival at 5 years was 94.9% vs 93.9% (HR = 0.88, 95% CI = 0.71–1.09, P = .25) among all patients, 94.4% vs 94.4% (HR = 1.05, 95% CI = 0.81–1.37, P = .70) among postmenopausal women, and 96.1% vs 92.8% (HR = 0.58, 95% CI = 0.39–0.87, P = .009) among premenopausal women.

The investigators concluded, “Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease–free survival and distant relapse–free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy.”

Disclosure: The study was funded by the National Cancer Institute, Susan G. Komen for the Cure Research Program, Hope Foundation for Cancer Research, Breast Cancer Research Foundation, and Genomic Health. For full disclosures of the study authors, visit nejm.org.