As reported in the Journal of Clinical Oncology by Mariana Chavez-MacGregor, MD, MSc, FASCO, and colleagues, the phase III SWOG S1207 trial showed no significant benefit in invasive disease–free survival with adjuvant endocrine therapy plus 1 year of everolimus vs 1 year of placebo in patients with high-risk, hormone receptor–positive, HER2-negative breast cancer after receipt of adjuvant or neoadjuvant chemotherapy.

Mariana Chavez-MacGregor, MD, MSc, FASCO

Study Details

In the U.S. multicenter trial, 1,792 patients were randomly assigned between September 2013 and May 2019 to receive physician’s choice of endocrine therapy plus 1 year of everolimus at 10 mg (n = 896) or placebo (n = 896) once daily. Endocrine therapy consisted of an aromatase inhibitor only in 63% of patients, tamoxifen only in 26%, ovarian function suppression plus tamoxifen or an aromatase inhibitor in 8% in the everolimus group, and an aromatase inhibitor only in 67% of patients, tamoxifen only in 24%, and ovarian function suppression plus tamoxifen or an aromatase inhibitor in 8% in the placebo group.

The primary endpoint of the trial was invasive disease–free survival.

Invasive Disease–Free Survival

At a median follow-up of 55 months, invasive disease–free survival events occurred in 193 patients in the everolimus group vs 211 patients in the placebo group (hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.77–1.14, P = .52). Invasive disease–free survival at 5 years was 74.9% (95% CI = 71.3%–78.0%) vs 74.4% (95% CI = 71.1%–77.4%), respectively. The proportional hazards assumption was violated; analysis showed that the hazard ratio was 0.75 (95% CI = 0.57–1.00) in years 0 to 2 and 1.16 (95% CI = 0.88–1.53) after 2 years.

Death occurred in 112 patients in the everolimus group vs 119 patients in the placebo group (HR = 0.97, 95% CI = 0.75–1.26, P = .84). Overall survival at 5 years was 88.1% (95% CI = 85.3%–90.3%) vs 85.8% (95% CI = 82.9%–88.2%), respectively.

In an unplanned subgroup analysis, no difference was observed between the everolimus group vs the placebo group in invasive disease–free survival (HR = 1.08, 95% CI = 0.86–1.36) or overall survival among 1,221 postmenopausal patients, but both invasive disease–free survival (HR = 0.64, 95% CI = 0.44–0.94) and overall survival benefits (HR = 0.49, 95% CI = 0.28–0.86) were observed with everolimus among 571 premenopausal patients.

Adverse Events

Grade ≥ 3 adverse events occurred in 35% of the everolimus/endocrine therapy group vs 7% of the placebo/endocrine therapy group; the most common in the everolimus group were stomatitis (7%), lymphopenia (4%) hypertriglyceridemia (4%), hyperglycemia (4%), fatigue (3%), and neutropenia (3%). Grade ≥ 3 pneumonitis was observed in seven patients in the everolimus group vs one patient in the placebo group. No treatment-related deaths were observed.  

The investigators concluded, “One year of adjuvant everolimus plus endocrine therapy did not improve overall outcomes. Subset analysis suggests mTOR inhibition as a possible target for patients who remain premenopausal after chemotherapy.”

Dr. Chavez-MacGregor, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute and by Novartis Pharmaceuticals Corporation. For full disclosures of the study authors, visit ascopubs.org.