New combination therapy for advanced HER2-positive breast cancer with a confirmed PIK3CA mutation

Breast cancer develops as a result of malignant changes in the cells of the breast’s glandular tissue, which multiply uncontrollably. There are various subtypes of the disease, which are distinguished based on the biological characteristics of the tumor cells. HER2 is a surface receptor on cancer cells that promotes tumor growth. For HER2-positive tumors, medications can be used that specifically bind to this receptor, inhibit the growth of cancer cells, and destroy them. Phesgo is a combination of the already approved drugs trastuzumab, pertuzumab, and rHuPH20 and is classified as a HER2-specific therapy. A common genetic alteration in cancer cells is the PIK3CA mutation. This mutation causes an alteration in the function of phosphoinositide 3-kinases (PI3K). These are enzymes that are normally responsible for cell division and cell growth. The mutation accelerates the formation and spread of cancer cells. Inavolisib is a novel drug that specifically inhibits these enzymes and is thus intended to slow the progression of breast cancer.

The INAVO-122 study is investigating the safety and efficacy of inavolisib in combination with Phesgo in patients with HER2-positive, PIK3CA-mutated breast cancer at the locally advanced or metastatic stage. Cancer is considered metastatic when cancer cells have spread beyond the breast to other parts of the body. Patients are randomly assigned to one of two groups. Neither the patients nor the treating physicians know which group they are in (double-blind). All patients will first receive treatment with Phesgo and standard taxane-based chemotherapy, with the specific chemotherapy regimen to be determined by the treating physician. Taxanes are among the established chemotherapeutic agents used in breast cancer treatment.

In the subsequent maintenance therapy designed to prolong the success of treatment, one group receives inavolisib in combination with Phesgo, while the other group receives a placebo with Phesgo. Maintenance therapy is intended to prevent the recurrence of the disease. Phesgo is injected under the skin every three weeks, while inavolisib or the placebo is taken daily as a tablet. Additional anti-hormone therapy is possible in accordance with guidelines. After the start of study treatment, patients will initially be monitored for 3.5 years to assess the course of the disease. The maximum follow-up period is up to 9.5 years after the start of the study. The study specifically examines progression-free survival (the length of time without disease progression), overall survival, as well as side effects and patients’ quality of life.

Adult women and men with locally advanced or metastatic HER2-positive breast cancer and a confirmed PIK3CA mutation are eligible to participate. Following prior chemotherapy, there must have been a disease-free period of at least six months.