S1207: Adding everolimus to endocrine therapy for high-risk breast cancer
Mariana Chavez-MacGregor, M.D., M.Sc., assistant professor of medicine at MD Anderson Cancer Center, is study coordinator for S1207. Expected to launch this fall, S1207 will test the addition of a year of everolimus to endocrine therapy in patients with high-risk breast cancer.
Phase III Randomized, Placebo-Controlled Clinical Trial Evaluating the Use of Adjuvant Endocrine Therapy +/- One Year of Everolimus in Patients with High-Risk, Hormone Receptor-Positive and Her2/Neu-Negative Breast Cancer
Patients with invasive hormone receptor-positive, HER2/NEU-negative breast cancer whose disease has spread to four or more lymph nodes or who have a recurrence score on the 21-gene Oncotype DX test higher than 25 have a substantial risk of breast cancer recurrence, even after surgery, chemotherapy, or radiation therapy. Such patients are generally prescribed five years of endocrine therapy with aromatase inhibitors or tamoxifen to reduce the level and/or the activity of the hormones that drive the cancer.
mTOR inhibitors such as everolimus have been shown to increase the activity of endocrine therapy, and S1207 is evaluating whether these patients can lower their risk of recurrence by adding a year of everolimus to standard endocrine therapy.
The phase III trial will enroll more than 3,000 patients and assign them at random to receive standard endocrine therapy alone, or standard endocrine therapy accompanied during the first year by a daily dose of 10 mg of everolimus.
The primary outcome being assessed is invasive disease-free survival (IDFS), with overall survival (OS) and distant recurrence-free survival (DRFS) as secondary measures. Investigators will also evaluate toxicity and patient adherence on the everolimus arm compared to that of standard endocrine therapy.
S1207 should be activated this fall.
Chemical structure of everolimus.
S1207's treatment objectives are coupled with a set of quality-of-life (QOL) related objectives being led by SWOG's sister cooperative group the National Surgical Adjuvant Breast Project (NSABP, now part of NRG Oncology) under the guidance of Patricia A. Ganz, M.D., of UCLA.
QOL objectives include comparing severity of fatigue, stomatitis, and musculoskeletal symptoms across the two arms during the first 48 weeks of treatment. Researchers will also look for correlations between increases in fatigue and other symptoms in those taking everolimus and increases in proinflammatory cytokines and other biomarkers of inflammation.
Stratified by risk
The S1207 treatment group will be stratified into four risk subgroups based on number of nodes involved and Oncotype DX Recurrence Score (RS). From lowest risk to highest, those are as follows.
- node-, RS > 25
- node+ (1-3 nodes), RS > 25
- ≥ 4 positive nodes (any RS) treated with adjuvant chemotherapy
- ≥ 4 positive nodes (any RS) prior to or after neoadjuvant chemotherapy
The stratum of node-negative patients will be capped at 50 percent of the accrual total.
Screening process aligned with RxPONDER (S1007)
"The ongoing RxPONDER trial (S1007) should be a significant source of potential S1207 participants, as the two trials are mutually exclusive in their eligibility," notes Mariana Chavez MacGregor, M.D., of MD Anderson Cancer Center, who is lead study coordinator for S1207. "Both trials draw from the pool of HR+, HER2- breast cancer patients."
RxPONDER uses the Oncotype DX 21-gene assay to screen HR+, HER2- patients with 1-3 positive lymph nodes. Those with a recurrence score of > 25 are not appropriate for S1007 but are likely to be eligible for S1207.
Directing patients to S1207 or RxPONDER (S1007)