New drug combination (alpelisib + fulvestrant) following prior anti-hormone and CDK4/6 inhibitor therapy in cases of disease progression

The treatment of advanced-stage breast cancer (mammary carcinoma) aims to “keep the disease in check” as much as possible, since a cure is often difficult to achieve. “Advanced” means that the tumor has reached a certain size and/or has already spread throughout the body (metastases). Treatment then depends primarily on the characteristics of the tumor cells, e.g., the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive) and the increased presence of HER2 receptors on the cells (HER2-positive). If hormone receptors are present, anti-hormone therapy is administered. For postmenopausal women, aromatase inhibitors are used as standard treatment; for some time now, these have been combined with another class of drugs known as CDK 4/6 inhibitors. If the disease progresses while on this treatment, another hormone-based medication, fulvestrant, may be used. Alpelisib is another drug that was approved a few years ago. This drug is particularly effective when there is a specific change in the cancer cells known as the PIK3CA mutation.

The goal of this Phase 3 study is to investigate the efficacy and safety of the combination therapy alpelisib + fulvestrant compared to fulvestrant alone in patients who have already been pretreated with a CDK inhibitor. Participants will be randomly assigned to one of two groups as part of the study. Group 1 (treatment arm) will receive alpelisib plus fulvestrant in 28-day cycles. Group 2 (control arm) will receive an alpelisib placebo (identical in appearance but without the active ingredient) plus fulvestrant. Alpelisib or the placebo is taken daily as a tablet, and fulvestrant is injected intramuscularly on Day 1 of each cycle (and once on Day 15 of the first cycle).

The study is double-blind, meaning that neither the medical staff nor the patient knows which medications are being administered. Treatments and follow-up examinations as part of the study will continue for up to 5 years, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factor is whether or when the disease recurs during therapy.

Postmenopausal women and men aged 18 and older with advanced hormone receptor-positive and HER2-negative breast cancer are eligible to participate in this study. In addition, participants must have a PIK3CA mutation and a recurrence (relapse) or progression of the disease following combination therapy with an aromatase inhibitor and a CDK inhibitor.