A new three-drug therapy has shown promising results in treating aggressive advanced breast cancer. The INAVO120 study, led by Professor Nicholas Turner at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, revealed that the combination of inavolisib, palbociclib, and fulvestrant doubles the time before cancer progresses compared to the standard treatment of palbociclib and fulvestrant. This breakthrough, published in the New England Journal of Medicine, offers a potential new standard of care for patients with PIK3CA-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. The FDA has already granted approval for this therapy.
Improved Progression-Free Survival
The phase III, randomized, double-blind trial demonstrated a significant improvement in progression-free survival. Patients receiving the inavolisib therapy experienced an average of 15 months before disease progression, compared to 7.3 months in the control group receiving palbociclib and fulvestrant, a combination approved for NHS use since September 2022. At 18 months, 46.2% of patients in the inavolisib group showed no signs of disease progression, compared to only 21.1% in the control group.
Targeting PIK3CA Mutations
PIK3CA mutations are present in 35-40% of HR+ breast cancers and are associated with tumor growth, disease progression, and treatment resistance. Inavolisib functions by blocking the activity of the PIK3CA protein and triggering the degradation of the mutated PI3K alpha protein. Palbociclib, a CDK4/6 inhibitor, prevents cancer cells from growing by blocking CDK4 and CDK6 proteins.
Study Details and Patient Population
The INAVO120 study involved 325 patients from 28 countries. A majority of the participants had metastatic disease that had spread to three or more organs, and 82.8% had prior chemotherapy. Researchers used ctDNA liquid biopsy tests to identify PIK3CA mutations. Participants were then randomized to receive either the inavolisib combination therapy or palbociclib, fulvestrant, and a placebo.
Impact and Future Directions
Professor Nick Turner emphasized the significance of the findings, stating, "This is the first study to demonstrate the potential of a therapy combination, which targets the three key aspects of the biology of PIK3CA mutant HR-positive breast cancer... This new combination helps prevent the cancer becoming resistant to therapy, and results in more frequent long-term responses." The researchers at the ICR's Centre for Cancer Drug Discovery are focused on developing new treatments that prevent drug resistance and alter the evolutionary paths of cancer.
