Trial Outcomes & Findings for Letrozole Plus Ribociclib or Placebo as Neo-adjuvant Therapy in ER-positive, HER2-negative Early Breast Cancer (NCT NCT02712723)

Last Updated: 2026-03-11

Results Overview

The Preoperative Endocrine Prognostic Index (PEPI) score 0 is defined as: pT stage 0, 1, or 2 at surgery after 24 weeks of neoadjuvant therapy; negative axillary lymph nodes at surgey; Ki67 of ≤ 2.7 % at surgery; and tumor is ER+ at surgery. A PEPI score of 0 predicts a good outcome compare to PEPI score \>0.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

121 participants

Primary outcome timeframe

24 weeks

Results posted on

2026-03-11

Participant Flow

Participant milestones

Participant milestones
Measure	Ribociclib 400 mg + Letrozole Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor	Placebo + Letrozole Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib	Ribociclib 600 mg + Letrozole Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor
Overall Study STARTED	41	38	41
Overall Study Received Treatment	41	37	41
Overall Study COMPLETED	28	28	32
Overall Study NOT COMPLETED	13	10	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Letrozole Plus Ribociclib or Placebo as Neo-adjuvant Therapy in ER-positive, HER2-negative Early Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Letrozole n=38 Participants Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib	Ribociclib 600 mg + Letrozole n=41 Participants Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor	Ribociclib 400 mg + Letrozole n=41 Participants Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor	Total n=120 Participants Total of all reporting groups
Age, Customized Median Age	66.5 years n=9 Participants	62.3 years n=9 Participants	65.7 years n=18 Participants	65.8 years n=15 Participants
Sex: Female, Male Female	38 Participants n=9 Participants	41 Participants n=9 Participants	41 Participants n=18 Participants	120 Participants n=15 Participants
Sex: Female, Male Male	0 Participants n=9 Participants	0 Participants n=9 Participants	0 Participants n=18 Participants	0 Participants n=15 Participants
Race/Ethnicity, Customized African American	2 Participants n=9 Participants	2 Participants n=9 Participants	7 Participants n=18 Participants	11 Participants n=15 Participants
Race/Ethnicity, Customized Asian	1 Participants n=9 Participants	2 Participants n=9 Participants	3 Participants n=18 Participants	6 Participants n=15 Participants
Race/Ethnicity, Customized Other	3 Participants n=9 Participants	3 Participants n=9 Participants	1 Participants n=18 Participants	7 Participants n=15 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=9 Participants	1 Participants n=9 Participants	2 Participants n=18 Participants	4 Participants n=15 Participants
Race/Ethnicity, Customized White	31 Participants n=9 Participants	33 Participants n=9 Participants	28 Participants n=18 Participants	92 Participants n=15 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: It was pre-specified as the primary endpoint in the Statistical Analysis Plan and the Study Protocol to compare Placebo therapy (Placebo + Letrozole) and combination therapy (Ribociclib + Letrozole).

Outcome measures

Outcome measures
Measure	Group A: Placebo + Letrozole n=38 Participants Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib	Group B and Group C (Combined) n=82 Participants Group B: Ribociclib intermittent + letrozole Group C: Ribociclib continuous z+ letrozole	Ribociclib 400 mg + Letrozole Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily
Rate of PEPI Score 0 at Surgery Between Ribociclib Containing Arms (Combined) vs. Letrozole Alone Arm.	21.1 percentage of participants	22.0 percentage of participants	—

SECONDARY outcome

Timeframe: Day 14 of Cycle 1

Population: It was pre-specified as the primary endpoint in the Statistical Analysis Plan and the Study Protocol to compare single therapy (Placebo + Letrozole) and combination therapy (Ribociclib + Letrozole).

Complete cell cycle arrest is defined as Ki67 at day 14 of \< 2.7.

Outcome measures

Outcome measures
Measure	Group A: Placebo + Letrozole n=38 Participants Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib	Group B and Group C (Combined) n=82 Participants Group B: Ribociclib intermittent + letrozole Group C: Ribociclib continuous z+ letrozole	Ribociclib 400 mg + Letrozole Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily
Rate of Complete Cell Cycle Arrest at 2 Weeks Between Ribociclib Containing Arms (Combined) vs Letrozole Alone Arm.	39.5 percentage of participants	82.9 percentage of participants	—

SECONDARY outcome

Timeframe: At Surgery (Days 8-15 of Cycle 6)

pCR is assciated with better outcomes in breast cancer

Outcome measures

Outcome measures
Measure	Group A: Placebo + Letrozole n=38 Participants Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib	Group B and Group C (Combined) n=41 Participants Group B: Ribociclib intermittent + letrozole Group C: Ribociclib continuous z+ letrozole	Ribociclib 400 mg + Letrozole n=41 Participants Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily
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	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Post-surgery (Once in the first 4 weeks of post-op, then once every 6 months for 5 years post-op)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years post-treatment

Outcome measures

Outcome data not reported

Adverse Events

Placebo + Letrozole

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

Ribociclib 600 mg + Letrozole

Serious events: 25 serious events

Other events: 21 other events

Deaths: 0 deaths

Ribociclib 400 mg + Letrozole

Serious events: 20 serious events

Other events: 23 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo + Letrozole n=37 participants at risk Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib	Ribociclib 600 mg + Letrozole n=41 participants at risk Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor	Ribociclib 400 mg + Letrozole n=41 participants at risk Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/37 • 6 months	2.4% 1/41 • 6 months	2.4% 1/41 • 6 months
Gastrointestinal disorders Vomiting	0.00% 0/37 • 6 months	0.00% 0/41 • 6 months	2.4% 1/41 • 6 months
Vascular disorders Hypertension	2.7% 1/37 • 6 months	2.4% 1/41 • 6 months	0.00% 0/41 • 6 months
Metabolism and nutrition disorders Hyperglycemia	5.4% 2/37 • 6 months	0.00% 0/41 • 6 months	0.00% 0/41 • 6 months
Investigations Alanine aminotransferase increased	0.00% 0/37 • 6 months	14.6% 6/41 • 6 months	14.6% 6/41 • 6 months
Investigations Neutrophil count decreased	0.00% 0/37 • 6 months	31.7% 13/41 • 6 months	7.3% 3/41 • 6 months
Gastrointestinal disorders Diarrhea	0.00% 0/37 • 6 months	0.00% 0/41 • 6 months	7.3% 3/41 • 6 months
Investigations Aspartate aminotransferase increased	0.00% 0/37 • 6 months	9.8% 4/41 • 6 months	7.3% 3/41 • 6 months
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/37 • 6 months	0.00% 0/41 • 6 months	2.4% 1/41 • 6 months
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/37 • 6 months	0.00% 0/41 • 6 months	4.9% 2/41 • 6 months

Other adverse events

Other adverse events
Measure	Placebo + Letrozole n=37 participants at risk Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib	Ribociclib 600 mg + Letrozole n=41 participants at risk Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor	Ribociclib 400 mg + Letrozole n=41 participants at risk Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor
Respiratory, thoracic and mediastinal disorders Cough	8.1% 3/37 • 6 months	14.6% 6/41 • 6 months	24.4% 10/41 • 6 months
Psychiatric disorders Insomnia	18.9% 7/37 • 6 months	4.9% 2/41 • 6 months	12.2% 5/41 • 6 months
Vascular disorders Hypertension	10.8% 4/37 • 6 months	4.9% 2/41 • 6 months	2.4% 1/41 • 6 months
Skin and subcutaneous tissue disorders Alopecia	8.1% 3/37 • 6 months	26.8% 11/41 • 6 months	22.0% 9/41 • 6 months
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	5.4% 2/37 • 6 months	9.8% 4/41 • 6 months	12.2% 5/41 • 6 months
Nervous system disorders Dizziness	13.5% 5/37 • 6 months	12.2% 5/41 • 6 months	19.5% 8/41 • 6 months
Investigations Creatinine increased	0.00% 0/37 • 6 months	12.2% 5/41 • 6 months	17.1% 7/41 • 6 months
Investigations Electrocardiogram QT corrected interval prolonged	2.7% 1/37 • 6 months	0.00% 0/41 • 6 months	24.4% 10/41 • 6 months
Metabolism and nutrition disorders Hyperglycemia	10.8% 4/37 • 6 months	4.9% 2/41 • 6 months	4.9% 2/41 • 6 months
Skin and subcutaneous tissue disorders Rash maculo-papular	5.4% 2/37 • 6 months	14.6% 6/41 • 6 months	12.2% 5/41 • 6 months
Reproductive system and breast disorders Breast pain	21.6% 8/37 • 6 months	2.4% 1/41 • 6 months	12.2% 5/41 • 6 months
Investigations White blood cell decreased	0.00% 0/37 • 6 months	17.1% 7/41 • 6 months	14.6% 6/41 • 6 months
Gastrointestinal disorders Vomiting	8.1% 3/37 • 6 months	9.8% 4/41 • 6 months	14.6% 6/41 • 6 months
Infections and infestations Urinary tract infection	16.2% 6/37 • 6 months	9.8% 4/41 • 6 months	12.2% 5/41 • 6 months
Nervous system disorders Dysgeusia	2.7% 1/37 • 6 months	7.3% 3/41 • 6 months	19.5% 8/41 • 6 months
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/37 • 6 months	17.1% 7/41 • 6 months	9.8% 4/41 • 6 months
Gastrointestinal disorders Mucositis oral	5.4% 2/37 • 6 months	14.6% 6/41 • 6 months	9.8% 4/41 • 6 months
Skin and subcutaneous tissue disorders Pruritus	5.4% 2/37 • 6 months	14.6% 6/41 • 6 months	12.2% 5/41 • 6 months
Metabolism and nutrition disorders Anorexia	0.00% 0/37 • 6 months	12.2% 5/41 • 6 months	17.1% 7/41 • 6 months
Gastrointestinal disorders Abdominal pain	2.7% 1/37 • 6 months	7.3% 3/41 • 6 months	12.2% 5/41 • 6 months
General disorders Localized edema	2.7% 1/37 • 6 months	4.9% 2/41 • 6 months	12.2% 5/41 • 6 months
Infections and infestations Upper respiratory infection	5.4% 2/37 • 6 months	12.2% 5/41 • 6 months	4.9% 2/41 • 6 months
General disorders Fatigue	40.5% 15/37 • 6 months	51.2% 21/41 • 6 months	56.1% 23/41 • 6 months
Musculoskeletal and connective tissue disorders Arthralgia	35.1% 13/37 • 6 months	29.3% 12/41 • 6 months	22.0% 9/41 • 6 months
Vascular disorders Hot flashes	51.4% 19/37 • 6 months	34.1% 14/41 • 6 months	48.8% 20/41 • 6 months
Gastrointestinal disorders Nausea	32.4% 12/37 • 6 months	43.9% 18/41 • 6 months	39.0% 16/41 • 6 months
Investigations Alanine aminotransferase increased	2.7% 1/37 • 6 months	29.3% 12/41 • 6 months	22.0% 9/41 • 6 months
Investigations Neutrophil count decreased	0.00% 0/37 • 6 months	46.3% 19/41 • 6 months	24.4% 10/41 • 6 months
Gastrointestinal disorders Diarrhea	16.2% 6/37 • 6 months	29.3% 12/41 • 6 months	31.7% 13/41 • 6 months
Investigations Aspartate aminotransferase increased	2.7% 1/37 • 6 months	31.7% 13/41 • 6 months	17.1% 7/41 • 6 months
Gastrointestinal disorders Constipation	13.5% 5/37 • 6 months	14.6% 6/41 • 6 months	29.3% 12/41 • 6 months
Nervous system disorders Headache	16.2% 6/37 • 6 months	34.1% 14/41 • 6 months	14.6% 6/41 • 6 months
Psychiatric disorders Anxiety	2.7% 1/37 • 6 months	4.9% 2/41 • 6 months	12.2% 5/41 • 6 months
Musculoskeletal and connective tissue disorders Myalgia	18.9% 7/37 • 6 months	14.6% 6/41 • 6 months	19.5% 8/41 • 6 months

Additional Information

Qamar Khan

UKansasMCRI

Phone: 9137106387

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place