A three-drug combination including inavolisib has shown promising results in extending progression-free survival for patients with advanced hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer harboring PIK3CA mutations. The INAVO120 trial, published in The New England Journal of Medicine, revealed that the combination of inavolisib, palbociclib, and fulvestrant nearly doubled the time before disease progression compared to a placebo-controlled regimen.
INAVO120 Trial Results
The international, multi-center INAVO120 trial involved 325 patients across 28 countries. The study focused on patients with PIK3CA-mutated HR+/HER2- breast cancer, a common subtype affecting approximately 70% of all breast cancer cases, with PIK3CA mutations present in 35-40% of HR+ cases. More than half of the participants had cancer that had spread to three or more organs, and over 80% had previously undergone chemotherapy.
Patients were randomized to receive either the three-drug combination (inavolisib, palbociclib, and fulvestrant) or a placebo plus palbociclib and fulvestrant. The results indicated a significant improvement in progression-free survival in the inavolisib arm, with a median of 15 months compared to 7.3 months in the placebo arm. At 18 months, 46.2% of patients in the three-drug group showed no signs of disease progression, compared to only 21.1% in the placebo group.
Expert Commentary
Lead author Nick Turner, a professor of molecular oncology at the Institute of Cancer Research, London, and consultant medical oncologist at the Royal Marsden NHS Foundation Trust, emphasized the significance of these 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," he stated. He further added that the combination helps prevent resistance to therapy, leading to more frequent and long-term responses.
Professor Kristian Helin, chief executive of the Institute of Cancer Research, London, highlighted the importance of overcoming drug resistance in cancer treatment. "By developing medicines with different mechanisms of action, we can block off cancer's escape routes and give people living with metastatic breast cancer the chance to live well for longer," he noted.
Implications for Treatment
The combination of palbociclib and fulvestrant has been available as a treatment option for certain breast cancer types since 2022. The addition of inavolisib to this regimen represents a significant advancement, particularly given the prevalence of PIK3CA mutations in HR+ breast cancers. The FDA has already approved the three-drug therapy, and researchers are optimistic that it will soon become a standard of care worldwide.
Dr Simon Vincent, director of research, support and influencing at Breast Cancer Now, noted that the findings could provide patients with secondary breast cancer an additional eight months without disease progression, offering them more time with their families. With approximately 61,000 individuals living with secondary breast cancer in the UK, this extended progression-free survival could have a substantial impact on patients' lives.
