ABCSG 43/INSEMA Details
An open-label, multicenter, Phase IIIb study to assess the safety and efficacy of ribociclib (LEE011) in combination with letrozole for the treatment of men and pre/postmenopausal women with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior hormonal therapy for advanced disease.
- Sample size:
- 5.940 (1. Randomization, international);
1.968 (2. randomization, international), 800 (2. randomization, national)
To compare the invasive disease-free survival after breast-conserving surgery (non-inferiority question)
- no axillary surgery vs. SLNB patients (first randomization)
- pN+(sn) with SLNB alone vs. pN+(sn) patients with completion ALND (second randomization)
To compare invasive disease-free survival after breast-conserving surgery
- no axillary surgery vs. pN0(sn) patients
- no axillary surgery vs. pN+(sn) patients with SLNB alone
- no axillary surgery vs. pN+(sn) patients with completion ALND
To compare overall survival between arms.
To compare locoregional disease-free survival (no tumor in the ipsilateral breast or ipsilateral supraclavicular, subclavicular, internal mammary or axillary nodes) between arms in both randomizations.
Ipsilateral axillary recurrence rate.
To compare distant disease-free survival between arms in both randomizations.
To compare the invasive disease-free survival between arms in subgroups according to age (<65 years vs. ≥65 years), tumor grading (G1/G2 vs. G3), tumor size (≤2 cm vs. >2 cm), delivered dose distribution in ipsilateral axilla levels I-III during postoperative whole-breast irradiation, and study site (German vs. Austrian sites in randomization 2).
To compare the safety and quality-of-life between arms and by subgroups.
- Written informed consent prior to beginning breast-conserving surgery, including expected cooperation of the patients for follow-up, must be obtained and documented according to the local regulatory requirements.
- Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy or open biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is planned.
- Age at diagnosis at least 18 years.
- Preoperative imaging techniques (mammography and sonography are mandatory) with estimated tumor size of ≤5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status).
- Clinically and sonographically tumor-free axilla prior to biopsy (cN0/iN0).
- In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration (FNA) biopsy of the sonographically suspected lymph node is required before randomization.
- No clinical evidence for distant metastasis (M0).
- Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation).
- History of malignancy within last 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix.
- Time since core/open biopsy >3 months (optimal <1 month).
- Previous and already (neoadjuvant) treated invasive breast carcinoma.
- Histologically non-invasive breast carcinoma.
- cT3/T4 or iT3/T4 tumors
- Pregnant or lactating patients.
- Planned total mastectomy.
- Planned intraoperative radiotherapy (e.g. Intrabeam) or postoperative partial breast irradiation (e.g. multicatheter technique) alone; both procedures are allowed as boost techniques.
- Male patients.