Investigating Atezolizumab in Newly Diagnosed ER Positive Breast Cancer Patients According to Their AdipOsity

Sponsor
Universitaire Ziekenhuizen KU Leuven
Study ID
NCT04630210
Phase
EARLY_PHASE1
Status
Withdrawn

Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Letrozole — DRUG
    Letrozole 2.5 mg/day oral until surgery
  • Atezolizumab — DRUG
    Atezolizumab 840 mg intravenous (IV) single-dose 14 days (+/- 4 days) before surgery

Study Details

One out of 8 women will develop breast cancer (BC) in her lifetime and despite improvements in therapeutic strategies it remains one of the main causes of cancer-related mortality for women in industrialized countries. Over the past decades another worldwide health problem has emerged: obesity. Around 50% of European women are either overweight or obese (body mass index (BMI)≥25 kg/m2: overweight; BMI≥30 kg/m2: obese). The global health effects of high BMI include the well-known elevated risk for developing cardiovascular disease and diabetes and a broad range of cancers, including in the breast. The connection between BC and obesity is gaining attention because of its clinical relevance. Heavier BC patients are generally older and tend to present with more aggressive disease (larger tumours and more frequent axillary lymph node dissemination). Likewise, they are also at higher risk of recurrence and resistance to therapy. This is of high importance, as development of therapy-resistant metastases is the ultimate cause of death in relapsing patients. Several molecular pathways linking the more aggressive BC nature to obesity have been proposed, such as oestrogens and fat cell signalling molecules, insulin signalling, metabolic inflammation and altered lipid metabolism. Adiposity is hardly taken into consideration in the treatment of BC patients. This is in contrast with the emerging trend to develop personalized therapies based on individual characteristics of the patient and molecular features of the tumour. Very recent data show that the upcoming treatment strategy of immunotherapy (IT) has better outcomes in obese patients in melanoma, renal cell and lung carcinoma. This could be explained by the fact that obesity induces T-cell dysregulation, which makes these patients more sensitive to IT. Whether or not this accounts for BC as well, is currently unknown. In endocrine BC treatment, research on the effect of BMI on treatment resistance is mainly retrospective and it is unclear whether heavier patients would present a differential benefit to aromatase inhibitors compared to lean patients. Also, most of these studies only considered BMI and no additional adiposity-related inflammation and other variables. Here, we therefore want to prospectively evaluate the local and systemic effects of aromatase inhibition and immunotherapy, either combined or alone, in a window of opportunity study carried out in luminal B like postmenopausal BC patients.

Key Dates

Start date
Feb 28, 2021
Status verified
May 2022
Primary completion
Jan 31, 2025
Completion
Jan 31, 2025

Study Design

Enrollment
0 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: A: Letrozole
    Letrozole 2.5 mg/day oral until surgery
  • Experimental: B: Letrozole + atezolizumab
    Letrozole 2.5 mg/day oral until surgery and Atezolizumab 840 mg intravenous (IV) single-dose 14 days (+/- 4 days) before surgery
  • Experimental: C: Atezolizumab
    Atezolizumab 840 mg IV single-dose 14 days (+/- 4 days) before surgery
  • No Intervention: D: Observation
    Observation until surgery

Primary Outcome Measure

Ki67 decrease [ Time Frame: At surgery ]

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