Study of Amcenestrant (SAR439859) Versus Tamoxifen for Patients With Hormone Receptor-positive (HR+) Early Breast Cancer, Who Have Discontinued Adjuvant Aromatase Inhibitor Therapy Due to Treatment-related Toxicity
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Amcenestrant; Tamoxifen; Amcenestrant-matching placebo; Tamoxifen-matching placebo
Intervention description: tablet, oral; tablet, oral; tablet, oral; tablet, oral
Intervention MeSH terms: Tamoxifen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double-dummy
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This was a phase III, randomized, double blind, multicenter, 2-arm study evaluating the
      efficacy and safety of amcenestrant compared with tamoxifen in participants with hormone
      receptor-positive early breast cancer who discontinued adjuvant aromatase inhibitor (AI)
      therapy due to treatment related toxicity. The primary objective was to demonstrate the
      superiority of amcenestrant versus tamoxifen on invasive breast cancer-free survival.

      The treatment duration per participant was to be 5 years, followed with a subsequent 5-years
      follow-up period. For the treatment period, visits were scheduled at the start of treatment,
      then at 4 weeks and 12 weeks after treatment start, and then every 12 weeks for the first 2
      years and every 24 weeks for year 3 to 5. For the follow-up period, visits were scheduled 30
      days after last treatment and then every 12 months. Three periods were planned:

        -  A screening period of up to 28 days,

        -  A treatment period of up to 5 years,

        -  A follow-up period of up to 5 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants with histologically confirmed diagnosis of adenocarcinoma of the
             breast with documentation of hormone receptor-positive status, irrespective of human
             epidermal growth factor receptor 2 (HER2) status NOTE: Participants with HER2-positive
             breast cancer were eligible only if they had completed their adjuvant anti-HER2
             treatment and chemotherapy.

          -  With Stage IIB or Stage III (invasive breast cancer) who had undergone breast surgery
             and adjuvant radiation (if indicated) for the current malignancy.

          -  Who had received prior aromatase inhibitors (AIs) (letrozole, anastrozole or
             exemestane or any sequence thereof) per the following:

        Adjuvant AI therapy was discontinued due to AI treatment-related toxicity; Minimum of 6
        months duration and maximum of 30 months duration (from initiation of first AI if there was
        a switch between AIs) of AI therapy was required.

          -  Absence of locoregional and/or advanced/metastatic disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

          -  Capable of giving signed informed consent.

        Exclusion Criteria:

          -  Medical history or ongoing gastrointestinal disorders potentially affecting the
             absorption of amcenestrant and/or tamoxifen. Participants unable to swallow normally
             or unable to take tablets and capsules. Predictable poor compliance to oral treatment.
             Active inflammatory bowel disease or chronic diarrhea, active hepatitis A/B/C, hepatic
             cirrhosis, short bowel syndrome, or any upper gastrointestinal surgery including
             gastric resection or banding procedures.

          -  History of prior breast cancer treated with AI.

          -  Any other solid tumor or lymphoma diagnosis was not allowed except if the participant
             had been free from disease for equal to greater than (=>5) years.

          -  Pregnant or nursing women, or women of child-bearing potential without a negative
             pregnancy test prior to randomization.

          -  Participants with unrecovered acute toxic effects of prior AI therapy or surgical
             procedures.

          -  Uncontrolled intercurrent illness, including psychiatric conditions that would have
             limited compliance with study requirements.

          -  Treatment with any selective estrogen receptor degrader (SERD), tamoxifen or
             toremifene were not allowed as prior adjuvant therapy but could have been used as
             neoadjuvant therapy for a total duration of 3 months. Participants who were treated
             with a SERD, tamoxifen or toremifene in the neoadjuvant setting and who experienced
             disease progression were not allowed. Prior treatment with raloxifene or tamoxifen for
             bone health, risk reduction, or a prior breast cancer was allowed provided this was
             discontinued at least 3 years before diagnosis of current breast cancer.

          -  Ongoing treatment with HER2 directed therapy. Appropriate wash out between the last
             dose of HER2 directed therapy and randomization should have been at least 4 weeks.

        The above information was not intended to contain all considerations relevant to a
        potential participation in a clinical trial.