To compare the combination of Ribociclib plus goserelin acetate with hormonal therapy versus combination chemotherapy in premenopausal or perimenopausal patients with advanced or metastatic breast cancer
Patients were randomly assigned to one of the below treatment arms in 1:1 ratio: * Ribociclib arm: non-steroidal aromatase inhibitor (NSAI) + goserelin + Ribociclib * Combination chemotherapy arm: Either of docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine based chemotherapy treatment Randomization was stratified by (1) the presence of liver metastases (present or absent) (2) disease-free interval (DFI) \< 2 years (yes or no, de novo stage 4 was defined as DFI \> 2 years). The study consisted of a 28-day Screening phase, treatment phase (including end of treatment (EOT) visit and safety follow-up), and survival follow-up. Patients received study treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. Patients were followed for survival regardless of treatment discontinuation for any reason (except if consent was withdrawn, patient was lost to follow-up, or until death) and regardless of achieving the primary endpoint, until death, withdrawal of consent, or loss to follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
222
Docetaxel (IV Infusion) / Capecitabine (Tablets for oral use): Docetaxel once, on day 1 of the 3-weeks cycle. Capecitabine twice daily, on Days 1 to 14, followed by a 1-week rest period, in 3 weeks cycle. Docetaxel (60 - 75 mg/m²)/capecitabine (1600 - 2500 mg/m²/day)
Capecitabine (Tablets for oral use) / Vinorelbine (Capsule for Oral use/IV infusion ). Capecitabine twice daily on day 1 to 14, followed by a 1-week rest period, in 3 weeks cycle. Vinorelbine, once, on Day 1 and Day 8 in 3 weeks cycles. Capecitabine (1600 - 2500 mg/m2/day)/vinorelbine (60 to 80 mg/m2/day \[oral\] or (25 to 30 mg/m2 \[IV infusion\]
Progression-free Survival
Progression-free survival was defined as the time from the date of randomization to the date of the first documented progression as per local review and according to RECIST 1.1 or death due to any cause. PFS was censored at the date of the last adequate tumor assessment if no PFS event was observed at the time of last patient, last visit (LPLV).
Time frame: Up to approximately 34 months
Time to Treatment Failure
Time to treatment failure was defined as the time from the date of randomization/start of treatment to the earliest of date of progression, date of death due to any cause, change to other anti-cancer therapy, or date of discontinuation due to reasons other than 'Protocol violation' or 'Administrative problems'. Patients who did not achieve a confirmed PR or CR were censored at: the maximum follow-up time (i.e., LPLV - first patient first visit \[FPFV\] used for the analysis) for patients who had a PFS event (i.e., either progressed or died due to any cause); the last adequate tumor assessment date for all other patients.
Time frame: Up to approximately 34 months
3-month Treatment Failure Rate
Treatment failure rate was defined as the percentage of patients who discontinued the study treatment due to progressive disease, death due to any cause, change to other anti-cancer therapy, or discontinuation due to reasons other than protocol violation or administrative problems.
Time frame: Up to approximately 3 months
Overall Response Rate (ORR)
Overall response rate (ORR) was defined as the percentage of patients with a best overall response (BOR) of complete response (CR) or partial response (PR, response without image confirmation), as per local review and according to RECIST 1.1.
Time frame: Up to approximately 34 months
Clinical Benefit Rate
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Paclitaxel (IV Infusion) / Gemcitabine (IV Infusion): Paclitaxel via 3-hour intravenous (IV) infusion on Day 1 in 3-weeks cycles, OR Paclitaxel via 1 hour intravenous (IV) infusion on Day 1 and day 8- in 3-weeks cycles. Gemcitabine at via 30 minute IV infusion on Day 1 and Day 8 in 3 weeks cycles. Paclitaxel (175 mg/m2) (on Day 1 in 3-weeks cycles)/ gemcitabine (1000 - 1250 mg/m2) OR Paclitaxel (80 - 90 mg/m2) (on Day 1 and Day 8 in 3-weeks cycles) / gemcitabine (800 - 1250 mg/m2)
Dose: 600 mg (200 mg \* 3) Days 1 to 21 of each 28 day cycle Tablets for oral use
Letrozole: Dose: 2.5 mg All days of every cycle without interruption). Tablets for oral use Anastrozole: dose: 1 mg All days of every cycle without interruption. Tablets for oral use The NSAI (letrozole or anastrozole) will be decided by the treating physician.
Dose: 3.6 mg Day 1 of each 28 day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days. Subcutaneous implant
Novartis Investigative Site
Cairo, Egypt
Novartis Investigative Site
Cairo, Egypt
Novartis Investigative Site
Cairo, Egypt
Novartis Investigative Site
Giza, Egypt
Novartis Investigative Site
Bangalore, Karnataka, India
Novartis Investigative Site
Pune, Maharashtra, India
Novartis Investigative Site
Hyderabad, Telangana, India
Novartis Investigative Site
Kolkata, West Bengal, India
Novartis Investigative Site
Mumbai, India
Novartis Investigative Site
New Delhi, India
...and 40 more locations
Clinical benefit rate was defined as the percentage of patients with a BOR of CR, PR, or stable disease (SD, response without image confirmation) lasting 24 weeks or longer, as defined by RECIST 1.1.
Time frame: Up to approximately 34 months
Time to Response
Time to response was defined as the time from the date of randomization to the first documented response of either CR or PR, which must be subsequently confirmed, as defined by RECIST 1.1. Patients who did not achieve a confirmed PR or CR were censored at: the maximum follow-up time (i.e., LPLV - FPFV used for the analysis) for patients who had a PFS event (i.e., either progressed or died due to any cause); the last adequate tumor assessment date for all other patients.
Time frame: Up to approximately 34 months
Overall Survival (OS)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a patient was not known to have died at the time of LPLV, then OS was censored at the last contact date.
Time frame: Up to approximately 46 months
Change From Baseline in the Global Health Status/Quality of Life (QOL) Scale Score by Using the Functional Assessment of Cancer Therapy - Breast (FACT-B) Questionnaire
FACT-B is a self-reported instrument that measures multidimensional quality of life (QOL) in patients with breast cancer. The FACT-B consists of 37 questions that address physical, social, emotional, and functional well-being, with specific questions relevant to women with breast cancer. Each item has a score range of 0 (Not at all) to 4 (Very much), with a total score ranging from 0-148. The higher the score, the better the QOL reported by the participant. A positive change from baseline indicates improvement in QoL.
Time frame: Up to approximately 46 months
Number of Patients With Adverse Events, Categorized by Severity
Adverse events were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or higher. If CTCAE grading did not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to Grades 1 - 4, were used. A patient with multiple severity grades for an AE was only counted under the maximum grade. Data for Grades 3 and 4 are reported.
Time frame: Up to approximately 46 months
Number of Patients With Laboratory Abnormalities
Grading of laboratory values was assigned programmatically as per NCI Common Terminology Criteria for Adverse Events (CTCAE) version available at the time of analysis. The calculation of CTCAE grades was based on the observed laboratory values only, clinical assessments were not be taken into account. CTCAE Grade 0 was assigned for all non-missing values not graded as 1 or higher. Grade 5 was not used. For laboratory tests where grades were not defined by CTCAE available at the time of analysis, results were categorized as low/normal/high based on laboratory normal ranges.
Time frame: Up to approximately 46 months
Post-Hoc: All Collected Deaths
On-treatment deaths due to any cause were collected from first dose of study medication to 30 days after the last dose of study treatment. Post-treatment survival follow-up deaths were collected from day 31 after last dose of study medication to end of study.
Time frame: On-treatment deaths: Up to approximately 46 months. Post-treatment survival follow-up deaths: Up to approximately 2 additional months.