SAR439859 plus palbociclib in ER (+), HER2 (-) breast cancer

• Research type

  Research Study

• Full title

  A randomized, multicenter, double-blind phase 3 study of SAR439859 plus palbociclib versus letrozole plus palbociclib for the treatment of patients with ER (+), HER2 (-) breast cancer who have not received prior systemic anti-cancer treatment for advanced disease.

• IRAS ID

  287474

• Contact name

  Lena Pedraut

• Contact email

  Lena.Pedraut@sanofi.com

• Sponsor organisation

  Sanofi-Aventis Recherche et Développement

• Eudract number

  2020-001824-33

• Clinicaltrials.gov Identifier

  NCT04478266

• Duration of Study in the UK

  5 years, 10 months, 11 days

• Research summary

  The purpose of the study is to evaluate whether SAR439859 (our experimental hormonal treatment) is a better option compared to Letrozole (a standard hormonal treatment), when given together with Palbociclib, in terms of efficacy and tolerance for treating patients with ER (+), HER2 (-) breast cancer.
  The study will be performed at NHS sites with clinical teams specialising in treatment on breast cancer.
  The study will last approximately 5 years. The study will be divided into 3 periods:
  Screening Period: Lasting up to 28 days to assess eligibility of patients to participate, which may need several visits to study site to perform all the required assessments.
  Treatment period: Divided into 28 day treatment cycles, with a scheduled visit at the beginning of each cycle. The average duration of this period will be approximately 2 years, and could vary depending up on how patients tolerate the study treatment or how their disease responds to study treatment. After your last study treatment, you will have an end-of-treatment visit that will occur around 30 days following the last administration of the study treatment
  Follow-up period: Starts after the end of study treatment, with a visit every 3 to 6 months, depending on patient’s disease status when they stopped the study treatment. The average duration of this period will be approximately 4 years.
  Patients will be allocated to one of two treatment arms at random, arm A (experimental arm) will receive SAR439859 given together with palbociclib and letrozole matching-placebo. Arm B (control arm) will receive Letrozole given together with palbociclib and SAR439859 matching-placebo. In both arms, pre/peri-menopausal women and men will receive goserelin injections every 28 days.

  Summary of Results
  Thank You to Study Participants

  First and foremost, we would like to express our sincere gratitude to all the participants who took part in this study. Your contribution is invaluable to advancing our understanding of breast cancer treatments.

  General Information About the Research

  Study Title
  A randomized, multicenter, double-blind Phase 3 study of amcenestrant (SAR439859) plus palbociclib versus letrozole plus palbociclib for the treatment of patients with ER (+), HER2 (-) breast cancer who have not received prior systemic anti-cancer treatment for advanced disease

  Who Carried Out the Research?
  This study was sponsored by Sanofi-Aventis Recherche & Développement.

  Where and When Did the Study Take Place?
  The study was conducted across 251 centers in 30 countries. It began on October 14, 2020, and was terminated early on August 17, 2022, based on an interim analysis.

  Why Was the Research Needed?
  Advanced breast cancer that is estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) is a challenging condition to treat. This study aimed to explore whether a new combination of drugs could improve outcomes for patients who had not yet received systemic treatment for their advanced disease.

  What Were the Main Questions Studied?
  The primary objective was to determine if the combination of amcenestrant plus palbociclib could improve progression-free survival (PFS) compared to the standard treatment of letrozole plus palbociclib in patients with ER+, HER2- advanced breast cancer.

  Who Participated in the Study?
  The study enrolled 1,068 patients with ER+, HER2- advanced or metastatic breast cancer who had not received prior systemic therapy for advanced disease.

  What Treatments Did the Participants Receive?
  Participants were randomly assigned to one of two groups:
  1. Amcenestrant 200 mg plus palbociclib 125 mg 2. Letrozole 2.5 mg plus palbociclib 125 mg

  What Happened During the Study?
  Patients received their assigned treatment and were monitored for disease progression and side effects. The study was planned to continue for longer, but it was stopped early based on the results of an interim analysis.

  What Were the Results of the Study?
  Unfortunately, the study did not show an improvement in progression-free survival with amcenestrant plus palbociclib compared to letrozole plus palbociclib:

  - The median PFS was 14.1 months for the amcenestrant plus palbociclib group.
  - The median PFS was 16.6 months for the letrozole plus palbociclib group.

  These results suggested that the standard treatment (letrozole plus palbociclib) performed better than the new combination.

  What Medical Problems (Adverse Reactions) Did the Participants Have?
  Both treatments were associated with side effects:

  - Severe side effects (Grade 3 or higher) occurred in 39% of patients receiving amcenestrant plus palbociclib and 54.8% of patients receiving letrozole plus palbociclib.
  - The most common severe side effects were low white blood cell counts (neutropenia), which were less frequent with amcenestrant plus palbociclib.
  - However, severe liver enzyme increases were more common with amcenestrant plus palbociclib.

  No new unexpected safety concerns were identified with the amcenestrant combination.

  How Has This Study Helped Patients and Researchers?
  While the results were not what we hoped for, this study has provided valuable information:

  1. It confirmed that the current standard treatment (letrozole plus palbociclib) remains an effective option for patients with ER+, HER2- advanced breast cancer.
  2. It helped researchers understand more about the effects of amcenestrant in combination with palbociclib, which can inform future research directions.
  3. The safety data collected will help doctors better understand and manage side effects in patients receiving these types of treatments.

• REC name

  London - Riverside Research Ethics Committee

• REC reference

  20/LO/1130

• Date of REC Opinion

  10 Nov 2020

• REC opinion

  Further Information Favourable Opinion