Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer.
Condition: Advanced Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Ribociclib; Fulvestrant; Placebo
Intervention description: Ribociclib capsules were administered orally at a daily dose of 600mg for 21 consecutive days within a 28-day cycle.; Fulvestrant was administered via intramuscular injections at a dose of 500mg every 28 days, starting on Day 1 of each cycle. In Cycle 1, an additional dose of Fulvestrant was given on Day 15.; Placebo capsules were administered orally for 21 consecutive days within a 28-day cycle.
Intervention MeSH terms: Fulvestrant
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Following protocol amendment 4 (29-Jan-2020), study participants were unblinded, with an opportunity for those patients still in the study in the arm of placebo + fulvestrant to transition to the treatment of ribociclib + fulvestrant.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 726.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HR-positive; HER2-negative; Advanced breast cancer; LEE011; ribociclib; fulvestrant; faslodex; CDK; CDK4; CDK6; CDK4/6; CDK4/6 inhibitor; Phase III; ER-positive; PR-positive; Postmenopausal; Men; Breast Neoplasms; Breast Diseases; Neoplasms; Neoplasms by Site; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Estrogen Receptor Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Therapeutic Use

Summary:

      The main aim of this study was to evaluate the efficacy and safety of adding ribociclib to
      fulvestrant in men and postmenopausal women with hormone receptor positive (HR+),
      HER2-negative advanced breast cancer.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Patients were adults, both male and female, aged ≥ 18 years at the time of providing
             informed consent. Female patients were required to be postmenopausal. Informed consent
             was obtained prior to any trial-related activities, following local guidelines.

          2. Patients had a confirmed diagnosis of estrogen-receptor positive and/or progesterone
             receptor positive breast cancer, determined through histological and/or cytological
             examination by a local laboratory. Patients also had HER2-negative breast cancer.

          3. Patients had either measurable disease as per RECIST 1.1 criteria or at least one
             predominantly lytic bone lesion.

          4. Patients had advanced breast cancer, which included locoregionally recurrent disease
             not amenable to curative therapies (such as surgery or radiotherapy) or metastatic
             breast cancer. Patients fell into one of the following categories:

               -  Newly diagnosed with advanced/metastatic breast cancer and treatment-naïve.

               -  Relapsed with documented evidence of relapse more than 12 months after completing
                  (neo)adjuvant endocrine therapy, without any prior treatment for
                  advanced/metastatic disease.

               -  Relapsed with documented evidence of relapse on or within 12 months from
                  completing (neo)adjuvant endocrine therapy, without any prior treatment for
                  advanced/metastatic disease.

               -  Relapsed with documented evidence of relapse more than 12 months after completing
                  adjuvant endocrine therapy and subsequently progressed after receiving one line
                  of endocrine therapy (antiestrogen or aromatase inhibitor) for
                  advanced/metastatic disease.

               -  Newly diagnosed with advanced/metastatic breast cancer at diagnosis and
                  progressed after receiving one line of endocrine therapy (antiestrogen or
                  aromatase inhibitor), with documented evidence of progression.

          5. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
             1.

          6. Patients had adequate bone marrow and organ function.

        Key Exclusion Criteria:

        Patients with symptomatic visceral disease or disease burden that rendered them ineligible
        for endocrine therapy, based on the investigator's judgment.

        2. Patients who had received prior treatment with chemotherapy (except for
        neoadjuvant/adjuvant chemotherapy), fulvestrant, or any CDK4/6 inhibitor.

        3. Patients with inflammatory breast cancer at the screening stage. 4. Patients with
        central nervous system (CNS) involvement, unless they were at least 4 weeks from completing
        prior therapy before initiating the study treatment and had a stable CNS tumor at the time
        of screening. They were also required not to be receiving steroids and/or enzyme-inducing
        anti-epileptic medications for brain metastases.

        5. Patients with clinically significant, uncontrolled heart disease and/or cardiac
        repolarization abnormality.

        6. Patients who were currently receiving any of the following substances, which could not
        be discontinued 7 days prior to initiating treatment:

          -  Known strong inducers or inhibitors of CYP3A4/5.

          -  Substances with a known risk of prolonging the QT interval or inducing Torsades de
             Pointes.

          -  Substances with a narrow therapeutic window and predominantly metabolized through
             CYP3A4/5.

          -  Herbal preparations/medications, dietary supplements.