A novel three-drug combination therapy, including inavolisib, has demonstrated a significant improvement in progression-free survival for patients with advanced hormone receptor-positive (HR+) breast cancer harboring PIK3CA mutations. The study, published in The New England Journal of Medicine, reveals that the combination of inavolisib, palbociclib, and fulvestrant nearly doubled the time patients lived without disease progression compared to a placebo-controlled regimen.
Improved Progression-Free Survival
The international Phase III trial involved 325 patients with advanced HR+/HER2- breast cancer across 28 countries. Participants were randomized to receive either inavolisib in combination with palbociclib and fulvestrant (n=161) or a placebo with palbociclib and fulvestrant (n=164). The results indicated a median progression-free survival of 15 months in the inavolisib arm compared to 7.3 months in the placebo arm. At 18 months, 46.2% of patients receiving the three-drug combination showed no signs of disease progression, versus 21.1% in the placebo group.
Targeting PI3K Pathway
Inavolisib is a PI3K inhibitor that targets the PI3K protein, a key driver of cancer growth in PIK3CA-mutated HR-positive breast cancers. PIK3CA mutations are present in approximately 35% to 40% of HR+ breast cancers. The combination therapy aims to block cancer growth by targeting multiple aspects of the PI3K signaling pathway.
Professor Nick Turner, lead author and a professor of molecular oncology at the Institute of Cancer Research, London, emphasized the significance of the findings: "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... It is a huge breakthrough that builds on a long programme of research at the ICR which could represent a transformative advance for people with this type of breast cancer."
Clinical Implications and Patient Impact
Breast cancer is a significant health challenge, with over 56,000 new cases diagnosed annually in the UK and almost 11,500 deaths. Approximately 70% of breast cancer patients have HR+/HER2- disease, and a substantial proportion of these tumors harbor PIK3CA mutations. For these patients, the inavolisib combination offers a promising new treatment option.
Anne Lury, a patient who participated in the trial, shared her experience: "After three years, the treatment stopped working for me, but, thankfully, I was able to receive inavolisib as part of a clinical trial... I wouldn’t be here if I hadn’t had the opportunity to join the trial at the Royal Marsden."
Regulatory Status and Availability
While the combination of palbociclib and fulvestrant has been available on the NHS since 2022 for certain breast cancer types, the three-drug therapy including inavolisib is not yet approved in the UK. However, the FDA in the USA recently granted approval for the inavolisib combination, paving the way for its potential use in other regions.
Dr. Simon Vincent, director of research, support, and influencing at Breast Cancer Now, noted the potential impact on patients with secondary breast cancer: "These findings show that this new treatment approach, using a combination of three drugs, could provide people living with secondary breast cancer an additional eight months without their disease getting worse, giving them precious more time with their loved ones."
