New First-Line Combination Therapy with Inavolisib for Advanced Hormone Receptor-Positive Breast Cancer with a PIK3CA Mutation

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue in which breast cells multiply uncontrollably. Treatment depends on various factors, including the stage of the disease and the biological characteristics of the tumor cells (such as hormone receptors and HER2 receptors). In hormone receptor-positive breast cancer, the cancer cells respond to the body’s own hormones—estrogen and progesterone—by growing; therefore, anti-hormonal therapy with aromatase inhibitors such as letrozole is used to block the effects of these hormones. CDK4/6 inhibitors are drugs that block certain enzymes (cyclin-dependent kinases 4 and 6), thereby inhibiting the division of cancer cells. This combination is the current standard of care. In addition, patients may have what is known as a PIK3CA mutation. This genetic alteration leads to the sustained activation of the PI3K signaling pathway, which promotes the growth and proliferation of cancer cells. The drug inavolisib is a so-called PI3K inhibitor that is taken as a tablet and specifically blocks this signaling pathway activated by the mutation. In Germany, the drug is already approved in combination with palbociclib and fulvestrant for the treatment of PIK3CA-mutated, hormone receptor-positive, HER2-negative, locally advanced, or metastatic breast cancer when the disease has recurred during adjuvant (supportive treatment given after surgery) anti-hormone therapy or within twelve months of its completion (endocrine-resistant).

The goal of this Phase 3 study is to investigate the safety and efficacy of the drug inavolisib when administered in addition to standard treatment. As part of the study, patients will be randomly assigned to two groups. In the treatment arm, patients will receive Inavolisib in combination with a CDK4/6 inhibitor and letrozole; in the control arm, patients will receive a placebo (an inactive drug) in combination with a CDK4/6 inhibitor and letrozole. All medications are taken as tablets. The study is double-blind, which means that neither the patients nor the treating study physicians know whether inavolisib or the placebo is being administered. The main objective (primary endpoint) of the study is to assess progression-free survival (PFS; the length of time during which the disease does not progress) for up to seven years.

Women and men aged 18 and older with advanced, hormone receptor-positive, HER2-negative breast cancer and a confirmed PIK3CA mutation are eligible to participate in this study. Both newly diagnosed and recurrent breast cancers that have not yet received treatment for the advanced stage are eligible. In the case of recurrent disease, it must be endocrine-sensitive; that is, it must not have recurred or progressed during a previous course of anti-hormone therapy lasting at least two years or within twelve months after the completion of such therapy.