Advanced Metastatic Breast Cancer
Conditions
Keywords
ribociclib, LEE011, RIBECCA, breast cancer, breast carcinoma, HR-positive, HER2-negative, advanced breast cancer, Letrozole, CDK4/6, breast lump, HER2 positive, metastatic breast cancer, breast cancer positive for human epidermal growth factor receptor 2 (HER2) HER2 positive metastatic breast cancer, breast cancer progression, estrogen-receptor (ER) positive(+) breast cancer, Paget's disease
Brief summary
This was a national, multi-center, open-label, phase IIIb trial to determine the efficacy and safety of treatment with ribociclib (LEE011) plus letrozole in patients with HR+, HER2-negative advanced (recurrent or metastatic) breast cancer. Patients were treated with daily doses of 600 mg ribociclib (3-weeks-on/1-week-off schedule) in combination with 2.5 mg letrozole daily (continuous dosing). Dose adjustments (dose reduction or interruption) according to safety findings were allowed.
Detailed description
The main purpose of this study was to collect additional efficacy and safety data for the combination of ribociclib and letrozole in a patient population broader than the MONALEESA-2 study (NCT01958021 / CLEE011A2301), and to provide access to ribociclib to patients for which available treatment options are unsatisfactory treatment alternatives until the drug is approved for this indication. Furthermore, this trial aimed to collect data for the combination of ribociclib and letrozole in the context of current local routine therapy algorithms for the treatment of metastatic and advanced breast cancer. This multi-center, open-label, single-arm study aimed to evaluate the efficacy, safety, and quality of life for the combination of ribociclib and letrozole in a patient population than in the MONALEESA-2 study, i.e. in patients pretreated with one line of chemotherapy and/or a maximum of two lines of endocrine therapy as well as premenopausal patients, without limitations regarding the disease free interval after adjuvant therapy. For ethical reasons no endocrine comparator drugs were investigated in this study. The duration of study treatment of 80 weeks was adequate to determine the primary, secondary and exploratory study parameters. The sample size was suitable to estimate the clinical benefit rate (CBR) in this patient population with reasonable precision. Goserelin was used in premenopausal patients, since it was shown that ovarian suppression of estrogen release with luteinizing hormone-releasing hormone agonists (LHRHa) (such as goserelin) is effective in preventing relapse in premenopausal women with early stage ER+ breast cancer (Klijn et al. 2001). The efficacy and safety of ribociclib in combination with letrozole for the treatment of postmenopausal women with advanced or metastatic breast cancer vs. placebo (i.e., letrozole alone) was already demonstrated in the preceding, pivotal MONALESSA-2 study. Thus, for ethical reasons no endocrine comparator drugs were investigated in the present RIBECCA study. Generally, the single-arm, open-label design and the broadening of the study population (compared to the pivotal MONALESSA-2 study) in the RIBECCA study was deemed appropriate to further evaluate the efficacy and safety of ribociclib plus letrozole among breast cancer patients in a treatment setting closer to routine care. The duration of study treatment of up to 80 weeks was considered adequate to determine the primary, secondary and exploratory study parameters. Moreover, the sample size was suitable to estimate the CBR in this patient population with reasonable precision.
Interventions
DRUGribociclib
All patients with oestrogen receptor positive advanced or metastatic breast cancer were treated with oral ribociclib at a dose of 600mg daily and oral letrozole 2.5mg daily. The study treatment for an individual patient began on Study Day 1 and continued until 80 weeks after the last patient enrolled the study or until disease progression, unacceptable toxicity, death or early discontinuation from the study for any other reason, whichever occured first.
DRUGletrozole
All patients with oestrogen receptor positive advanced or metastatic breast cancer were treated with oral ribociclib at a dose of 600mg daily and oral letrozole 2.5mg daily. The study treatment for an individual patient began on Study Day 1 and continued until 80 weeks after the last patient enrolled the study or until disease progression, unacceptable toxicity, death or early discontinuation from the study for any other reason, whichever occured first.
DRUGgoserelin
Premenopausal patients additionally received goserelin 3.6mg as monthly implant
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is an adult, ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines * Women and men with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy. * Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive and HER2-negative breast cancer by local laboratory. Local pathology is sufficient for assessment. * Patient must have either: 1. Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria ). 2. Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease 3. Non-measurable disease * Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
Exclusion criteria
* Patient who received any CDK4/6 inhibitor or any mTOR inhibitor. * Patient has a known hypersensitivity to any of the excipients of ribociclib or letrozole * Patients with current inflammatory breast cancer. * Patient has received \> 1 chemotherapy for the treatment of advanced/metastatic breast cancer * Patient has received \> 2 endocrine therapies for the treatment of advanced/metastatic breast cancer * Patient has central nervous system (CNS) involvement. If patient is fulfilling the following 3 criteria she/he is eligible for the trial. 1. completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of study and 2. CNS tumor is clinically stable at the time of screening and 3. Patient is not receiving steroids and enzyme inducing anti-epileptic medications for brain metastases * Patient has active cardiac disease or a history of cardiac dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | At 24 weeks after last patient enrolled in trial | Clinical Benefit Rate (CBR) after 24 weeks of treatment as defined by RECIST 1.1 as percentage of patients with Complete Response (CR), Partial response (PR) or Stable disease (SD) lasting 24 weeks or longer as well as patients with Non-complete response, nonprogressive disease (NCRNPD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) for Different Populations - Median Time to Progression or Death With 95% CI [Months] | Up to approximately month 25 | PFS based on radiologic assessment by investigator using RECIST 1.1 criteria |
| Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | At Week 24, Week 48 and Week 72 | Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause. For the Kaplan-Meier estimates (%, 95% CI), the probability of survival at week 24, 48 and 72 is reported below. |
| Overall Survival (OS) - Median Time to Progression or Death With 95% CI [Months] | Up to approximatley 38 months | Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause. |
| Overall Survival (OS) - Number of Censored Participants and Number of Deaths | Up to approximatley 38 months | Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause. |
| Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | At week 24 , week 48 and week 72 | PFS based on radiologic assessment by investigator using RECIST 1.1 criteria |
| Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Change from Baseline to Week 24 | The QLQ-C30 is the core questionnaire of the EORTC QLQ, which has been developed for the assessment of the health-related QOL of cancer patients participating in international clinical trials. Using a linear transformation to standardize the raw scores, all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher (better) level of functioning (applies to the first 6 items, items 1 to 6), but a higher (worse) level of symptoms (applies to the last 9 items, items 7 to 15). There is no aggregated total score, i.e., all scale scores were analyzed separately. |
| Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | Baseline and Week 24 (Cycle 7) | To evaluate health related quality of life (QoL) via EORTC BR-23. The scoring approach for the QLQ-BR23 is identical in principle to that for the function and symptom scales / single items of the QLQ-C30, i.e., all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher (better) level of functioning, (applies to the first 4 items, items 1 to 4) but a higher (worse) level of symptoms (applies to the last 4 items, items 5 to 8). |
| Time to 10% Deterioration in EORTC Global Health Status | up to approximately 10 months | Time to 10% deterioration in the European Organisation for Research and Treatment of Cancer (EORTC) global health status |
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | Up to Week 72 | Adverse Events (AEs) were separated into TEAEs (defined as AEs occurring/worsening from first study drug treatment until 30 days after the last study drug treatment) and AEs in the pre-/post-treatment period. |
| Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) | At week 24 | Overall response rate (ORR) is the best overall response (BOR) of complete response (CR) or partial response (PR) as defined by RECIST 1.1. |
Countries
Germany
Participant flow
Pre-assignment details
504 participants were entered into the study, but 2 of these participants were not treated. The full analysis set is comprised of the 504 participants minus 17 participants, whose data were removed because of inspection findings, to equal 487 participants. This full analysis set includes the 2 participants who were entered into the study but were not treated. 502 participants were treated; these 502 participants are included in the safety set.
Participants by arm
| Arm | Count |
|---|---|
| Ribociclib + Letrozole Cohort A postmenopausal women, or men; naïve.
All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily. | 319 |
| Ribociclib + Letrozole Cohort B1 premenopausal women or perimenopausal women; naïve
All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.
Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly | 26 |
| Ribociclib + Letrozole Cohort B2 premenopausal women or perimenopausal women or postmenopausal women, or men; pre-treated.
All patients received ribociclib 600mg p.o. daily + Letrozole 2.5 mg p.o. daily.
Premenopausal patients additionally received goserelin 3.6 mg i.m. monthly | 157 |
| Total | 502 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 72 | 6 | 28 |
| Overall Study | Death | 6 | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | New therapy for study indication | 1 | 0 | 1 |
| Overall Study | Non-compliance with study medication | 1 | 0 | 0 |
| Overall Study | Other | 2 | 1 | 2 |
| Overall Study | Physician Decision | 12 | 2 | 8 |
| Overall Study | Progressive disease | 97 | 10 | 78 |
| Overall Study | Protocol Violation | 3 | 0 | 6 |
| Overall Study | Withdrawal by Subject | 24 | 1 | 12 |
Baseline characteristics
| Characteristic | Ribociclib + Letrozole Cohort A | Ribociclib + Letrozole Cohort B1 | Ribociclib + Letrozole Cohort B2 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 176 Participants | 0 Participants | 70 Participants | 246 Participants |
| Age, Categorical Between 18 and 65 years | 143 Participants | 26 Participants | 87 Participants | 256 Participants |
| Age, Continuous | 65.7 Years STANDARD_DEVIATION 10.1 | 46.5 Years STANDARD_DEVIATION 4.9 | 62.8 Years STANDARD_DEVIATION 12.8 | 63.8 Years STANDARD_DEVIATION 11.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 0 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) White | 312 Participants | 24 Participants | 151 Participants | 487 Participants |
| Sex: Female, Male Female | 315 Participants | 26 Participants | 156 Participants | 497 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 319 | 6 / 183 | 0 / 26 | 6 / 157 | 12 / 502 |
| other Total, other adverse events | 315 / 319 | 181 / 183 | 25 / 26 | 156 / 157 | 496 / 502 |
| serious Total, serious adverse events | 97 / 319 | 50 / 183 | 5 / 26 | 45 / 157 | 147 / 502 |
Outcome results
Primary
Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole
Clinical Benefit Rate (CBR) after 24 weeks of treatment as defined by RECIST 1.1 as percentage of patients with Complete Response (CR), Partial response (PR) or Stable disease (SD) lasting 24 weeks or longer as well as patients with Non-complete response, nonprogressive disease (NCRNPD).
Time frame: At 24 weeks after last patient enrolled in trial
Population: Full Analysis Set. Please note that the statistical significance test (test comparing groups) i.e., statistical analysis was not applicable for this outcome measure, since the primary objective was to assess the rate (per cohort) and not to compare two or more treatment arms, as this was a non-randomized, single arm open label trial.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ribociclib + Letrozole Cohort A | Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | CBR by week 24 (= BOR of CR or PR or SD or NCRNPD(Confirmed Best Overall Response (BOR)) | 63.2 Percentage of Participants |
| Ribociclib + Letrozole Cohort A | Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | CBR by week 24 (= BOR of CR or PR or SD or NCRNPD (non-confirmed BOR) | 71.7 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | CBR by week 24 (= BOR of CR or PR or SD or NCRNPD (non-confirmed BOR) | 69.2 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | CBR by week 24 (= BOR of CR or PR or SD or NCRNPD(Confirmed Best Overall Response (BOR)) | 57.7 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | CBR by week 24 (= BOR of CR or PR or SD or NCRNPD(Confirmed Best Overall Response (BOR)) | 56.5 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | CBR by week 24 (= BOR of CR or PR or SD or NCRNPD (non-confirmed BOR) | 64.3 Percentage of Participants |
| Total | Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | CBR by week 24 (= BOR of CR or PR or SD or NCRNPD(Confirmed Best Overall Response (BOR)) | 60.8 Percentage of Participants |
| Total | Clinical Benefit Rate (CBR) in Women and Men With Hormone Receptor Positiv, HER-2 Negative Breast Cancer Treated With Ribocilib and Letrozole | CBR by week 24 (= BOR of CR or PR or SD or NCRNPD (non-confirmed BOR) | 69.2 Percentage of Participants |
Secondary
Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30
The QLQ-C30 is the core questionnaire of the EORTC QLQ, which has been developed for the assessment of the health-related QOL of cancer patients participating in international clinical trials. Using a linear transformation to standardize the raw scores, all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher (better) level of functioning (applies to the first 6 items, items 1 to 6), but a higher (worse) level of symptoms (applies to the last 9 items, items 7 to 15). There is no aggregated total score, i.e., all scale scores were analyzed separately.
Time frame: Change from Baseline to Week 24
Population: Full Analysis Set. Included in the analysis are all patients with valid assessment at baseline and week 24. Some questions were conditional branching and thus did not apply to some participants. Also, some participants chose not to answer some questions / items; the responses were accepted as provided by the participants. Also, some participants discontinued during the course of the trial, and thus less measurements were taken at week 24 than at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Diarrhea - Change from baseline to Week 24 (C7D1) | 2.6 Scores on a scale | Standard Deviation 24.6 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Nausea / Vomiting - Change from baseline to Week 24 (C7D1) | 0.1 Scores on a scale | Standard Deviation 16.7 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Fatigue - Change from baseline to Week 24 (C7D1) | 6.3 Scores on a scale | Standard Deviation 25.9 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Cognitive Functioning - Change from baseline to Week 24 (C7D1) | 2.7 Scores on a scale | Standard Deviation 23.7 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Constipation - Change from baseline to Week 24 (C7D1) | -2.7 Scores on a scale | Standard Deviation 26.6 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Social Functioning - Change from baseline to Week 24 (C7D1) | -6.9 Scores on a scale | Standard Deviation 27.9 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Physical Functioning - Change from baseline to Week 24 (C7D1) | -3.1 Scores on a scale | Standard Deviation 19.9 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Global health status - Change from baseline to Week 24 (C7D1) | 8.8 Scores on a scale | Standard Deviation 23.7 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Appetite loss - Change from baseline to Week 24 (C7D1) | 11.2 Scores on a scale | Standard Deviation 33.7 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Insomnia - Change from baseline to Week 24 (C7D1) | 4.2 Scores on a scale | Standard Deviation 33.2 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Role Functioning - Change from baseline to Week 24 (C7D1) | -6.6 Scores on a scale | Standard Deviation 31.9 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Financial Problems - Change from baseline to Week 24 (C7D1) | 0.2 Scores on a scale | Standard Deviation 27.7 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Dyspnoea - Change from baseline to Week 24 (C7D1) | 3.8 Scores on a scale | Standard Deviation 32.4 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Pain - Change from baseline to Week 24 (C7D1) | 13.2 Scores on a scale | Standard Deviation 31.9 |
| Ribociclib + Letrozole Cohort A | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Emotional Functioning - Change from baseline to Week 24 (C7D1) | -9.6 Scores on a scale | Standard Deviation 24.2 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Appetite loss - Change from baseline to Week 24 (C7D1) | 6.7 Scores on a scale | Standard Deviation 28.7 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Global health status - Change from baseline to Week 24 (C7D1) | 11.7 Scores on a scale | Standard Deviation 20.8 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Physical Functioning - Change from baseline to Week 24 (C7D1) | -3.6 Scores on a scale | Standard Deviation 10.7 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Role Functioning - Change from baseline to Week 24 (C7D1) | -17 Scores on a scale | Standard Deviation 21.8 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Emotional Functioning - Change from baseline to Week 24 (C7D1) | -9.4 Scores on a scale | Standard Deviation 25 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Cognitive Functioning - Change from baseline to Week 24 (C7D1) | 2.2 Scores on a scale | Standard Deviation 28.1 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Social Functioning - Change from baseline to Week 24 (C7D1) | -16 Scores on a scale | Standard Deviation 21.3 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Fatigue - Change from baseline to Week 24 (C7D1) | 11.1 Scores on a scale | Standard Deviation 20.6 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Nausea / Vomiting - Change from baseline to Week 24 (C7D1) | 1.1 Scores on a scale | Standard Deviation 22.2 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Pain - Change from baseline to Week 24 (C7D1) | 15.6 Scores on a scale | Standard Deviation 24.8 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Dyspnoea - Change from baseline to Week 24 (C7D1) | 4.4 Scores on a scale | Standard Deviation 21.3 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Insomnia - Change from baseline to Week 24 (C7D1) | 6.7 Scores on a scale | Standard Deviation 31.4 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Constipation - Change from baseline to Week 24 (C7D1) | 2.2 Scores on a scale | Standard Deviation 26.6 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Diarrhea - Change from baseline to Week 24 (C7D1) | 0.0 Scores on a scale | Standard Deviation 45.4 |
| Ribociclib + Letrozole Cohort B1 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Financial Problems - Change from baseline to Week 24 (C7D1) | -4.4 Scores on a scale | Standard Deviation 24.8 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Role Functioning - Change from baseline to Week 24 (C7D1) | -1.3 Scores on a scale | Standard Deviation 34.7 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Appetite loss - Change from baseline to Week 24 (C7D1) | 1.4 Scores on a scale | Standard Deviation 30.9 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Financial Problems - Change from baseline to Week 24 (C7D1) | -1.4 Scores on a scale | Standard Deviation 25.1 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Dyspnoea - Change from baseline to Week 24 (C7D1) | -5.3 Scores on a scale | Standard Deviation 30.5 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Nausea / Vomiting - Change from baseline to Week 24 (C7D1) | -4.9 Scores on a scale | Standard Deviation 19.1 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Constipation - Change from baseline to Week 24 (C7D1) | -3.6 Scores on a scale | Standard Deviation 27.9 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Diarrhea - Change from baseline to Week 24 (C7D1) | 2.3 Scores on a scale | Standard Deviation 27.2 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Cognitive Functioning - Change from baseline to Week 24 (C7D1) | 1.1 Scores on a scale | Standard Deviation 21.6 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Pain - Change from baseline to Week 24 (C7D1) | 9.0 Scores on a scale | Standard Deviation 27.6 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Social Functioning - Change from baseline to Week 24 (C7D1) | -5.3 Scores on a scale | Standard Deviation 31.3 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Insomnia - Change from baseline to Week 24 (C7D1) | 4.9 Scores on a scale | Standard Deviation 32.7 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Physical Functioning - Change from baseline to Week 24 (C7D1) | -2.2 Scores on a scale | Standard Deviation 17.7 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Global health status - Change from baseline to Week 24 (C7D1) | 5.0 Scores on a scale | Standard Deviation 26.2 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Fatigue - Change from baseline to Week 24 (C7D1) | 3.9 Scores on a scale | Standard Deviation 27.1 |
| Ribociclib + Letrozole Cohort B2 | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Emotional Functioning - Change from baseline to Week 24 (C7D1) | -3.6 Scores on a scale | Standard Deviation 21.8 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Fatigue - Change from baseline to Week 24 (C7D1) | 5.1 Scores on a scale | Standard Deviation 26.1 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Nausea / Vomiting - Change from baseline to Week 24 (C7D1) | -3.9 Scores on a scale | Standard Deviation 19.7 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Role Functioning - Change from baseline to Week 24 (C7D1) | -3.9 Scores on a scale | Standard Deviation 33.3 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Diarrhea - Change from baseline to Week 24 (C7D1) | 1.9 Scores on a scale | Standard Deviation 30.7 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Dyspnoea - Change from baseline to Week 24 (C7D1) | -3.7 Scores on a scale | Standard Deviation 29.3 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Physical Functioning - Change from baseline to Week 24 (C7D1) | -2.4 Scores on a scale | Standard Deviation 16.7 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Insomnia - Change from baseline to Week 24 (C7D1) | 5.2 Scores on a scale | Standard Deviation 32.3 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Pain - Change from baseline to Week 24 (C7D1) | 10.1 Scores on a scale | Standard Deviation 27.1 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Appetite loss - Change from baseline to Week 24 (C7D1) | 2.2 Scores on a scale | Standard Deviation 30.5 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Global health status - Change from baseline to Week 24 (C7D1) | 6.1 Scores on a scale | Standard Deviation 25.4 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Financial Problems - Change from baseline to Week 24 (C7D1) | -1.9 Scores on a scale | Standard Deviation 24.9 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Cognitive Functioning - Change from baseline to Week 24 (C7D1) | 1.3 Scores on a scale | Standard Deviation 22.7 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Constipation - Change from baseline to Week 24 (C7D1) | -2.6 Scores on a scale | Standard Deviation 27.6 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Social Functioning - Change from baseline to Week 24 (C7D1) | -7.0 Scores on a scale | Standard Deviation 30 |
| Total | Change From Baseline at Week 24 of Patient Reported Quality of Life (QoL) Via EORTC QLQ-C30 | Emotional Functioning - Change from baseline to Week 24 (C7D1) | -4.6 Scores on a scale | Standard Deviation 22.4 |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Adverse Events (AEs) were separated into TEAEs (defined as AEs occurring/worsening from first study drug treatment until 30 days after the last study drug treatment) and AEs in the pre-/post-treatment period.
Time frame: Up to Week 72
Population: Safety Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ribociclib + Letrozole Cohort A | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs with fatal outcome | 6 Number of Participants |
| Ribociclib + Letrozole Cohort A | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Total AEs (i.e., Includes any type of AE.) | 318 Number of Participants |
| Ribociclib + Letrozole Cohort A | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Non-serious AEs | 317 Number of Participants |
| Ribociclib + Letrozole Cohort A | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs with suspected relationship to ribociclib | 302 Number of Participants |
| Ribociclib + Letrozole Cohort A | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Serious AEs | 97 Number of Participants |
| Ribociclib + Letrozole Cohort A | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs leading to discontinuation of ribociclib | 76 Number of Participants |
| Ribociclib + Letrozole Cohort B1 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Total AEs (i.e., Includes any type of AE.) | 25 Number of Participants |
| Ribociclib + Letrozole Cohort B1 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs leading to discontinuation of ribociclib | 7 Number of Participants |
| Ribociclib + Letrozole Cohort B1 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs with fatal outcome | 0 Number of Participants |
| Ribociclib + Letrozole Cohort B1 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Serious AEs | 5 Number of Participants |
| Ribociclib + Letrozole Cohort B1 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Non-serious AEs | 25 Number of Participants |
| Ribociclib + Letrozole Cohort B1 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs with suspected relationship to ribociclib | 25 Number of Participants |
| Ribociclib + Letrozole Cohort B2 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs with fatal outcome | 6 Number of Participants |
| Ribociclib + Letrozole Cohort B2 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Total AEs (i.e., Includes any type of AE.) | 157 Number of Participants |
| Ribociclib + Letrozole Cohort B2 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Serious AEs | 45 Number of Participants |
| Ribociclib + Letrozole Cohort B2 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs with suspected relationship to ribociclib | 144 Number of Participants |
| Ribociclib + Letrozole Cohort B2 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | AEs leading to discontinuation of ribociclib | 38 Number of Participants |
| Ribociclib + Letrozole Cohort B2 | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Non-serious AEs | 157 Number of Participants |
Secondary
Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI)
Overall response rate (ORR) is the best overall response (BOR) of complete response (CR) or partial response (PR) as defined by RECIST 1.1.
Time frame: At week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ribociclib + Letrozole Cohort A | Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) | ORR by week 24 - (BOR of CR or PR) (confirmed) | 22.8 Percentage of Participants |
| Ribociclib + Letrozole Cohort A | Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) | ORR by week 24 - (BOR of CR or PR) (unconfirmed) | 24.8 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) | ORR by week 24 - (BOR of CR or PR) (confirmed) | 23.1 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) | ORR by week 24 - (BOR of CR or PR) (unconfirmed) | 30.8 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) | ORR by week 24 - (BOR of CR or PR) (confirmed) | 11.7 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Overall Response Rate (ORR) - Kaplan-Meier Estimates (%, 95% CI) | ORR by week 24 - (BOR of CR or PR) (unconfirmed) | 16.2 Percentage of Participants |
Secondary
Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI)
Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause. For the Kaplan-Meier estimates (%, 95% CI), the probability of survival at week 24, 48 and 72 is reported below.
Time frame: At Week 24, Week 48 and Week 72
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ribociclib + Letrozole Cohort A | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 72 | 89.7 Percentage of Participants |
| Ribociclib + Letrozole Cohort A | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 48 | 93.3 Percentage of Participants |
| Ribociclib + Letrozole Cohort A | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 24 | 98.6 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 48 | 87.5 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 24 | 100.0 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 72 | 87.5 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 24 | 93.9 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 72 | 81.0 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Overall Survival (OS) - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 48 | 86.1 Percentage of Participants |
Secondary
Overall Survival (OS) - Median Time to Progression or Death With 95% CI [Months]
Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause.
Time frame: Up to approximatley 38 months
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ribociclib + Letrozole Cohort A | Overall Survival (OS) - Median Time to Progression or Death With 95% CI [Months] | NA Months |
| Ribociclib + Letrozole Cohort B1 | Overall Survival (OS) - Median Time to Progression or Death With 95% CI [Months] | NA Months |
| Ribociclib + Letrozole Cohort B2 | Overall Survival (OS) - Median Time to Progression or Death With 95% CI [Months] | NA Months |
Secondary
Overall Survival (OS) - Number of Censored Participants and Number of Deaths
Overall survival (OS) defined as the time from date of start of treatment to date of death due to any cause.
Time frame: Up to approximatley 38 months
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ribociclib + Letrozole Cohort A | Overall Survival (OS) - Number of Censored Participants and Number of Deaths | No. of censored (no death), n | 240 Participants |
| Ribociclib + Letrozole Cohort A | Overall Survival (OS) - Number of Censored Participants and Number of Deaths | No. of events (deaths due to any cause), n | 67 Participants |
| Ribociclib + Letrozole Cohort B1 | Overall Survival (OS) - Number of Censored Participants and Number of Deaths | No. of censored (no death), n | 17 Participants |
| Ribociclib + Letrozole Cohort B1 | Overall Survival (OS) - Number of Censored Participants and Number of Deaths | No. of events (deaths due to any cause), n | 9 Participants |
| Ribociclib + Letrozole Cohort B2 | Overall Survival (OS) - Number of Censored Participants and Number of Deaths | No. of censored (no death), n | 94 Participants |
| Ribociclib + Letrozole Cohort B2 | Overall Survival (OS) - Number of Censored Participants and Number of Deaths | No. of events (deaths due to any cause), n | 60 Participants |
Secondary
Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7)
To evaluate health related quality of life (QoL) via EORTC BR-23. The scoring approach for the QLQ-BR23 is identical in principle to that for the function and symptom scales / single items of the QLQ-C30, i.e., all scores finally range from 0 to 100, where a higher score represents a higher response level, e.g., a higher (better) level of functioning, (applies to the first 4 items, items 1 to 4) but a higher (worse) level of symptoms (applies to the last 4 items, items 5 to 8).
Time frame: Baseline and Week 24 (Cycle 7)
Population: Full Analysis Set. Included in the analysis are all patients with valid assessment at baseline and week 24. Some questions were conditional branching and thus did not apply to some participants. Also, some participants chose not to answer some questions / items; the responses were accepted as provided by the participants. Also, some participants discontinued during the course of the trial, and thus less measurements were taken at week 24 than at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ribociclib + Letrozole Cohort A | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 BODY IMAGE during the study - change from baseline at cycle 7 | -1.5 Scores on a scale | Standard Deviation 18.2 |
| Ribociclib + Letrozole Cohort A | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SEXUAL FUNCTIONING during the study - change from baseline at cycle 7 | -1.1 Scores on a scale | Standard Deviation 17.7 |
| Ribociclib + Letrozole Cohort A | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SEXUAL ENJOYMENT during the study - change from baseline at cycle 7 | -1.9 Scores on a scale | Standard Deviation 31.3 |
| Ribociclib + Letrozole Cohort A | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 FUTURE PERSPECTIVE during the study - change from baseline at cycle 7 | -20 Scores on a scale | Standard Deviation 33.4 |
| Ribociclib + Letrozole Cohort A | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SYSTEMATIC THERAPY during the study - change from baseline at cycle 7 | -9.4 Scores on a scale | Standard Deviation 16.6 |
| Ribociclib + Letrozole Cohort A | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 BREAST SYMPTOMS during the study - change from baseline at cycle 7 | 3.3 Scores on a scale | Standard Deviation 15.7 |
| Ribociclib + Letrozole Cohort A | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 ARM SYMPTOMS during the study - change from baseline at cycle 7 | 4.1 Scores on a scale | Standard Deviation 21.1 |
| Ribociclib + Letrozole Cohort A | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 HAIR LOSS during the study - change from baseline at cycle 7 | -22 Scores on a scale | Standard Deviation 43.4 |
| Ribociclib + Letrozole Cohort B1 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 BREAST SYMPTOMS during the study - change from baseline at cycle 7 | 8.3 Scores on a scale | Standard Deviation 22.7 |
| Ribociclib + Letrozole Cohort B1 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SYSTEMATIC THERAPY during the study - change from baseline at cycle 7 | -13 Scores on a scale | Standard Deviation 22.3 |
| Ribociclib + Letrozole Cohort B1 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SEXUAL FUNCTIONING during the study - change from baseline at cycle 7 | 0.0 Scores on a scale | Standard Deviation 24.5 |
| Ribociclib + Letrozole Cohort B1 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 HAIR LOSS during the study - change from baseline at cycle 7 | -17 Scores on a scale | Standard Deviation 23.6 |
| Ribociclib + Letrozole Cohort B1 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 ARM SYMPTOMS during the study - change from baseline at cycle 7 | -1.5 Scores on a scale | Standard Deviation 22.6 |
| Ribociclib + Letrozole Cohort B1 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 FUTURE PERSPECTIVE during the study - change from baseline at cycle 7 | -24 Scores on a scale | Standard Deviation 26.6 |
| Ribociclib + Letrozole Cohort B1 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SEXUAL ENJOYMENT during the study - change from baseline at cycle 7 | -17 Scores on a scale | Standard Deviation 23.6 |
| Ribociclib + Letrozole Cohort B1 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 BODY IMAGE during the study - change from baseline at cycle 7 | -0.6 Scores on a scale | Standard Deviation 22.2 |
| Ribociclib + Letrozole Cohort B2 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 ARM SYMPTOMS during the study - change from baseline at cycle 7 | -2.1 Scores on a scale | Standard Deviation 18.1 |
| Ribociclib + Letrozole Cohort B2 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SEXUAL ENJOYMENT during the study - change from baseline at cycle 7 | 7.4 Scores on a scale | Standard Deviation 26.9 |
| Ribociclib + Letrozole Cohort B2 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 FUTURE PERSPECTIVE during the study - change from baseline at cycle 7 | -12 Scores on a scale | Standard Deviation 26.2 |
| Ribociclib + Letrozole Cohort B2 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SYSTEMATIC THERAPY during the study - change from baseline at cycle 7 | -6.0 Scores on a scale | Standard Deviation 14.9 |
| Ribociclib + Letrozole Cohort B2 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 BREAST SYMPTOMS during the study - change from baseline at cycle 7 | 0.9 Scores on a scale | Standard Deviation 17.5 |
| Ribociclib + Letrozole Cohort B2 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 HAIR LOSS during the study - change from baseline at cycle 7 | -14 Scores on a scale | Standard Deviation 33.9 |
| Ribociclib + Letrozole Cohort B2 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 BODY IMAGE during the study - change from baseline at cycle 7 | 0.4 Scores on a scale | Standard Deviation 22.7 |
| Ribociclib + Letrozole Cohort B2 | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SEXUAL FUNCTIONING during the study - change from baseline at cycle 7 | 0.8 Scores on a scale | Standard Deviation 18 |
| Total | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SEXUAL ENJOYMENT during the study - change from baseline at cycle 7 | 5.0 Scores on a scale | Standard Deviation 27.1 |
| Total | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 FUTURE PERSPECTIVE during the study - change from baseline at cycle 7 | -14 Scores on a scale | Standard Deviation 26.5 |
| Total | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SEXUAL FUNCTIONING during the study - change from baseline at cycle 7 | 0.7 Scores on a scale | Standard Deviation 19.1 |
| Total | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 BODY IMAGE during the study - change from baseline at cycle 7 | 0.2 Scores on a scale | Standard Deviation 22.5 |
| Total | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 SYSTEMATIC THERAPY during the study - change from baseline at cycle 7 | -7.1 Scores on a scale | Standard Deviation 16.4 |
| Total | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 HAIR LOSS during the study - change from baseline at cycle 7 | -15 Scores on a scale | Standard Deviation 32.1 |
| Total | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 ARM SYMPTOMS during the study - change from baseline at cycle 7 | -2.0 Scores on a scale | Standard Deviation 18.8 |
| Total | Patient Reported Quality of Life (QoL) Via EORTC BR-23 - Change From Baseline at Week 24 (Cycle 7) | EORTC QLQ-BR23 BREAST SYMPTOMS during the study - change from baseline at cycle 7 | 2.2 Scores on a scale | Standard Deviation 18.6 |
Secondary
Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI)
PFS based on radiologic assessment by investigator using RECIST 1.1 criteria
Time frame: At week 24 , week 48 and week 72
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ribociclib + Letrozole Cohort A | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 48 | 61.9 Percentage of Participants |
| Ribociclib + Letrozole Cohort A | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 24 | 73.1 Percentage of Participants |
| Ribociclib + Letrozole Cohort A | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - week 72 | 54.5 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 48 | 58.7 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 24 | 67.0 Percentage of Participants |
| Ribociclib + Letrozole Cohort B1 | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - week 72 | 49.6 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 24 | 63.8 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - week 72 | 39.3 Percentage of Participants |
| Ribociclib + Letrozole Cohort B2 | Progression Free Survival (PFS) for Different Populations - Kaplan-Meier Estimates (%, 95% CI) | Kaplan-Meier estimates (%, 95% CI) - Week 48 | 47.5 Percentage of Participants |
Secondary
Progression Free Survival (PFS) for Different Populations - Median Time to Progression or Death With 95% CI [Months]
PFS based on radiologic assessment by investigator using RECIST 1.1 criteria
Time frame: Up to approximately month 25
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ribociclib + Letrozole Cohort A | Progression Free Survival (PFS) for Different Populations - Median Time to Progression or Death With 95% CI [Months] | 21.8 Months |
| Ribociclib + Letrozole Cohort B1 | Progression Free Survival (PFS) for Different Populations - Median Time to Progression or Death With 95% CI [Months] | 16.5 Months |
| Ribociclib + Letrozole Cohort B2 | Progression Free Survival (PFS) for Different Populations - Median Time to Progression or Death With 95% CI [Months] | 8.8 Months |
Secondary
Time to 10% Deterioration in EORTC Global Health Status
Time to 10% deterioration in the European Organisation for Research and Treatment of Cancer (EORTC) global health status
Time frame: up to approximately 10 months
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ribociclib + Letrozole Cohort A | Time to 10% Deterioration in EORTC Global Health Status | 3.3 months |
| Ribociclib + Letrozole Cohort B1 | Time to 10% Deterioration in EORTC Global Health Status | 3.7 months |
| Ribociclib + Letrozole Cohort B2 | Time to 10% Deterioration in EORTC Global Health Status | 2.8 months |
| Total | Time to 10% Deterioration in EORTC Global Health Status | 3.0 months |
Post Hoc
All Collected Deaths
On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 1150 days (approx 3.15 years). (Treatment duration ranged from 2 days to 1120 days). Deaths post treatment survival follow up were collected after the on- treatment period, up to approx. 3.15 years. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.
Time frame: on-treatment deaths: up to approx 3.15 years; all deaths: approx 3.15 years
Population: Clinical database population - all treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ribociclib + Letrozole Cohort A | All Collected Deaths | Total deaths | 67 Participants |
| Ribociclib + Letrozole Cohort A | All Collected Deaths | on-treatment deaths | 6 Participants |
| Ribociclib + Letrozole Cohort B1 | All Collected Deaths | on-treatment deaths | 0 Participants |
| Ribociclib + Letrozole Cohort B1 | All Collected Deaths | Total deaths | 9 Participants |
| Ribociclib + Letrozole Cohort B2 | All Collected Deaths | Total deaths | 60 Participants |
| Ribociclib + Letrozole Cohort B2 | All Collected Deaths | on-treatment deaths | 6 Participants |
| Total | All Collected Deaths | Total deaths | 136 Participants |
| Total | All Collected Deaths | on-treatment deaths | 12 Participants |