Subjects will be randomized (1:1:1) to either letrozole plus placebo vs. letrozole plus
continuous dosing of ribociclib vs. letrozole plus intermittent dosing
(3-weeks-on/1-week-off) of ribociclib.
The difference in clinical, pathologic and radiologic response as well as Pre-operative
Endocrine Prognostic Index (PEPI) scores across the three treatments arms will be examined.
Subjects will also be followed for 5 years post-treatment to determine if ribociclib in
combination with letrozole for 24 weeks results in improved 5 year Relapse Free Survival
(RFS) compared to letrozole alone.
Key Inclusion Criteria:
- Pathologically confirmed invasive breast cancer by core needle biopsy
- Female subjects, age 18 years
- Only postmenopausal women will be eligible.
- Performance Status: Eastern Cooperative Oncology Group (ECOG) score 0-2
- Invasive breast cancer must be ER+ in >66 % of the cells or ER Allred score 6-8
- Invasive breast cancer must be HER2 negative.
- Clinical Stage II or III
Key Exclusion Criteria:
- Subjects meeting any of the exclusion criteria at baseline will be excluded from
- Current use of other investigational agents
- Inflammatory breast cancer defined as clinically significant erythema of the breast
and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or
peau d'orange without erythema)
- An excisional biopsy of this breast cancer
- Surgical axillary staging procedure prior to study entry
- Hormone replacement therapy of any type, megestrol acetate, or raloxifene within four
weeks prior to first study treatment
- Clinical or radiographic evidence of metastatic disease
- Clinically significant, uncontrolled heart disease
- Herbal preparations/medications as listed in Appendix B of the protocol
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female
Rate of complete cell cycle arrest at 2 weeks between ribociclib containing arms (combined) vs letrozole alone arm: Complete cell cycle arrest is defined as Ki67 at day 14 of < 2.7%
Pathologic complete response rate (pCR rate): pCR rate is defined as the proportion of patients with no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes
Clinical complete response rate (cCR rate): cCR rate is defined as the proportion of patients with no residual tumor by clinical exam
5 Year Relapse Free Survival (RFS)