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NCT01958021: MONALEESA-2

Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer

Completed Phase 3 Results posted Last updated 7 March 2025
What this trial tests

Phase 3 trial testing Ribociclib in Advanced, Metastatic Breast Cancer in 668 participants. Completed in 16 March 2023.

Timeline
17 December 2013
Primary endpoint
29 January 2016
16 March 2023

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment668
Start date17 December 2013
Primary completion29 January 2016
Estimated completion16 March 2023
Sites221 locations across Italy, Finland, Taiwan, Ireland, South Korea, Lebanon, Denmark, Netherlands

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 100, female only, with Advanced, Metastatic Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) by Investigator Assessment Primary · Up to 23 months

PFS was defined as the period starting from the date of randomization to the date of the first documented progression or death caused by any reason. In cases where patients did not experience an event, the PFS was censored at the date of the last adequate tumor assessment. Clinical deterioration without objective radiological evidence was not considered as documented disease progression.PFS was assessed by investigator assessment according to RECIST 1.1. The Kaplan-Meier method was used to estimate PFS, and the median PFS, along with 95% confidence intervals, was reported for each treatment gr

GroupValue95% CI
Ribociclib + LetrozoleNA19.3 – NA
Placebo + Letrozole14.713.0 – 16.5
Overall Survival (OS) Secondary · Up to approximately 87 months

OS was defined as the time from the date of randomization to the date of death from any cause. In cases where the patient's death was not recorded, the OS value was censored at the date of the last known patient's survival status.OS was estimated using the Kaplan-Meier method. As per protocol, the final OS analysis was conducted after approximately 400 deaths were documented. The median OS, along with 95% confidence intervals, was reported for each treatment group.The distribution of OS between the two treatment arms was compared using a log-rank test at one-sided cumulative 2.5% level of sig

GroupValue95% CI
Ribociclib + Letrozole63.952.4 – 71.0
Placebo + Letrozole51.447.2 – 59.7
Overall Response Rate (ORR) by Investigator Assessment Secondary · Up to 23 months

ORR is the percentage of participants with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 as per investigator assessment. . CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

GroupValue95% CI
Ribociclib + Letrozole40.735.4 – 46.0
Placebo + Letrozole27.522.8 – 32.3
Clinical Benefit Rate (CBR) by Investigator Assessment Secondary · Up to 23 months

Percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1 as per investigator assessment. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progress

GroupValue95% CI
Ribociclib + Letrozole79.675.3 – 84.0
Placebo + Letrozole72.868.0 – 77.5
Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score Secondary · From baseline up to 23 months

ECOG PS categorized patients based on their ability to perform daily activities and self-care, with scores ranging from 0 to 5. A score of 0 indicated no restrictions in activity, while higher scores indicated increasing limitations. Time to definitive deterioration was defined as the time from the date of randomization to the date of the event, defined as experiencing an increase in ECOG PS by at least one category from the baseline or death. A deterioration was considered definitive if no improvements in the ECOG PS were observed at a subsequent time. The Kaplan-Meier method was used to esti

GroupValue95% CI
Ribociclib + Letrozole22.622.6 – NA
Placebo + LetrozoleNANA – NA
Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (GHS/QoL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30) Secondary · From baseline up to 23 months

The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The time to definitive 10% deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10% relative to baseline worsening of the QoL score (without further improvement above the threshold) or death due to any cause. The Kaplan-Meier method was used to estimate the distribution, and the median time to defi

GroupValue95% CI
Ribociclib + Letrozole19.316.6 – 22.1
Placebo + LetrozoleNA14.8 – NA
Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30 Secondary · Baseline, every 2 cycles for 18 months, then every 3 cycles until last dose; at EOT (within 15 days from last dose);every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to 23 months. Cycle=28 days

The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The change from baseline in the GHS/QoL score was assesed. A positive change from baseline indicated improvement. For subjects who discontinued treatment earlier and without disease progression, post-treatment efficacy follow-up visits occurred every 8 weeks after End of treatment (EOT) during the initial 18 months since start of treatment, followed by visits ev

Cycle 3 Day 1
GroupValue95% CI
Ribociclib + Letrozole2.9± 18.68
Placebo + Letrozole4.9± 19.14
Cycle 5 Day 1
GroupValue95% CI
Ribociclib + Letrozole4.6± 19.86
Placebo + Letrozole6.8± 19.64
Cycle 7 Day 1
GroupValue95% CI
Ribociclib + Letrozole4.6± 20.96
Placebo + Letrozole6.0± 20.19
Cycle 9 Day 1
GroupValue95% CI
Ribociclib + Letrozole5.1± 21.95
Placebo + Letrozole8.0± 20.49
Cycle 11 Day 1
GroupValue95% CI
Ribociclib + Letrozole4.9± 21.11
Placebo + Letrozole7.0± 20.45
Cycle 13 Day 1
GroupValue95% CI
Ribociclib + Letrozole5.3± 22.37
Placebo + Letrozole6.5± 20.40
Cycle 15 Day 1
GroupValue95% CI
Ribociclib + Letrozole5.5± 21.43
Placebo + Letrozole8.7± 21.23
Cycle 17 Day 1
GroupValue95% CI
Ribociclib + Letrozole4.6± 22.85
Placebo + Letrozole7.4± 21.75
All Collected Deaths Secondary · Pre-treatment: Up to 21 days. On-treatment: Up to 99 months. Crossover on-treatment: Up to 12 months after crossing-over.Post-treatment survival FU: Up to 99 months.Crossover post-treatment survival FU: Up to 12 months after crossing-over

Pre-treatment deaths were collected from randomization to the day before first dose of study medication. On-treatment deaths were collected from start of treatment to 30 days after last dose of treatment or one day before first administration of crossover treatment (for crossover participants), whichever came first Crossover on-treatment deaths were collected from start of crossover treatment up to 30 days after last dose of crossover treatment. Post-treatment survival follow-up (FU) deaths were collected from day 31 after last dose of study treatment to end of study. Crossover post-treatme

Pre-treatment
GroupValue95% CI
Ribociclib + Letrozole0
Placebo + Letrozole0
On-treatment
GroupValue95% CI
Ribociclib + Letrozole8
Placebo + Letrozole3
Crossover On-treatment
GroupValue95% CI
Placebo + Letrozole0
Post-treatment survival follow-up
GroupValue95% CI
Ribociclib + Letrozole178
Placebo + Letrozole218
Crossover post-treatment survival follow-up
GroupValue95% CI
Placebo + Letrozole0
All deaths
GroupValue95% CI
Ribociclib + Letrozole186
Placebo + Letrozole221

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality (ACM): from randomization up to 99 months, including post-treatment survival follow-up (FU). If crossover, ACM also collected from start of crossover treatment to 12 months, including post-treatment survival FU. Serious and Other Adverse Events (AEs): from 1st dose of treatment to 30 days after last dose (or start of crossover treatment), up to 99 months. If crossover, AEs also collected from start of crossover treatment to 30 days post-crossover treatment, up to 12 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ribociclib + Letrozole
Serious: 108/334 (32%)
Deaths: 8/334
Placebo + Letrozole
Serious: 62/330 (19%)
Deaths: 3/334
Crossover to Ribociclib + Letrozole
Serious: 1/4 (25%)
Deaths: 0/4
Ribociclib + Letrozole (Post-treatment Survival Follow-up)
Serious: 0
Deaths: 178/278
Placebo + Letrozole (Post-treatment Survival Follow-up)
Serious: 0
Deaths: 218/298
Crossover to Ribociclib + Fulvestrant (Crossover Post-treatment Survival Follow-up)
Serious: 0
Deaths: 0/4

Serious adverse events (198 terms)

ReactionSystemRibociclib + LetrozolePlacebo + LetrozoleCrossover to Ribociclib + …Ribociclib + Letrozole (Po…Placebo + Letrozole (Post-…Crossover to Ribociclib + …
PneumoniaInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
General physical health deteriorationGeneral disorders
DizzinessNervous system disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
DehydrationMetabolism and nutrition disorders
SyncopeNervous system disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Non-cardiac chest painGeneral disorders
HepatotoxicityHepatobiliary disorders
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
Aspartate aminotransferase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Acute kidney injuryRenal and urinary disorders
Coronary artery diseaseCardiac disorders
Other adverse events (86 terms — click to expand)

ReactionSystemRibociclib + LetrozolePlacebo + LetrozoleCrossover to Ribociclib + …Ribociclib + Letrozole (Po…Placebo + Letrozole (Post-…Crossover to Ribociclib + …
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
AlopeciaSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
HeadacheNervous system disorders
Back painMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
Hot flushVascular disorders
Neutrophil count decreasedInvestigations
AnaemiaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
HypertensionVascular disorders
White blood cell count decreasedInvestigations
RashSkin and subcutaneous tissue disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
LeukopeniaBlood and lymphatic system disorders
InsomniaPsychiatric disorders
DizzinessNervous system disorders
StomatitisGastrointestinal disorders
Urinary tract infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
AstheniaGeneral disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Dry mouthGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Bone painMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
AnxietyPsychiatric disorders
Lacrimation increasedEye disorders
DyspepsiaGastrointestinal disorders
NasopharyngitisInfections and infestations
Blood creatinine increasedInvestigations

Most-reported serious reactions: Pneumonia, Dyspnoea, Abdominal pain, Nausea, Vomiting, General physical health deterioration, Dizziness, Anaemia.

Data from ClinicalTrials.gov NCT01958021 adverse events section.

Sponsor's own description

The primary purpose of this study was to assess the efficacy of ribociclib, as measured by progression free survival (PFS), in postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who received no prior treatment for advanced disease.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.
    Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, et al · · 2016 · cited 1435× · PMID 27717303 · DOI 10.1056/nejmoa1609709
  2. Targeting CDK4 and CDK6: From Discovery to Therapy.
    Sherr CJ, Beach D, Shapiro GI. · · 2016 · cited 729× · PMID 26658964 · DOI 10.1158/2159-8290.cd-15-0894
  3. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer.
    Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, et al · · 2018 · cited 597× · PMID 29718092 · DOI 10.1093/annonc/mdy155
  4. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer.
    Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, et al · · 2022 · cited 533× · PMID 35263519 · DOI 10.1056/nejmoa2114663
  5. Cyclin D1, cancer progression, and opportunities in cancer treatment.
    Qie S, Diehl JA. · · 2016 · cited 527× · PMID 27695879 · DOI 10.1007/s00109-016-1475-3
  6. The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer.
    Ding L, Cao J, Lin W, Chen H, et al · · 2020 · cited 385× · PMID 32183020 · DOI 10.3390/ijms21061960
  7. Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer.
    Ye F, Dewanjee S, Li Y, Jha NK, et al · · 2023 · cited 361× · PMID 37415164 · DOI 10.1186/s12943-023-01805-y
  8. CDK4 and CDK6 kinases: From basic science to cancer therapy.
    Fassl A, Geng Y, Sicinski P. · · 2022 · cited 351× · PMID 35025636 · DOI 10.1126/science.abc1495

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