The New England Journal of Medicine has published results from the Phase III INAVO120 trial, showcasing Roche's Itovebi (inavolisib) in combination with palbociclib and fulvestrant as a significant advancement in treating HR-positive, HER2-negative advanced breast cancer with PIK3CA mutations. The study demonstrated a substantial improvement in progression-free survival (PFS) and a promising trend in overall survival (OS).
Doubling Progression-Free Survival
The INAVO120 trial revealed that the Itovebi-based regimen reduced the risk of disease progression or death by 57% compared to palbociclib and fulvestrant alone (HR=0.43, 95% CI: 0.32-0.59, p<0.001). The median PFS improved from 7.3 months in the control arm to 15.0 months in the Itovebi arm. This benefit was consistently observed across all pre-specified subgroups, including patients with disease spread to three or more locations.
Clinical Significance and FDA Approval
The U.S. Food and Drug Administration (FDA) recently approved Itovebi in combination with palbociclib and fulvestrant as a first-line treatment for adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer. This approval marks a significant step forward in addressing the unmet needs of this patient population.
Overall Survival Trend
While the overall survival (OS) data were immature at the time of analysis, a positive trend was observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.03). Follow-up for OS is ongoing to the next analysis, which may further solidify the long-term benefits of the Itovebi-based regimen.
Addressing PIK3CA Mutations in Breast Cancer
The PIK3CA mutation is present in approximately 40% of HR-positive metastatic breast cancers and is associated with a poor prognosis. Identifying these mutations through early biomarker testing, such as Foundation Medicine’s FoundationOne®Liquid CDx, is crucial to ensure that patients receive the most appropriate targeted therapy.
Expert Commentary
"With a doubling of progression-free survival and consistent benefits in people whose disease had spread to multiple challenging-to-treat locations, including the liver and lungs, these INAVO120 data are significant for patients," said Komal Jhaveri, M.D., section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and one of the principal investigators of the INAVO120 study. "I’m confident this Itovebi-based regimen could become a new first-line standard of care for this patient population with one of the most commonly mutated genes in metastatic breast cancer, associated with a poor prognosis."
Ongoing Research
Itovebi is currently being investigated in three company-sponsored phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations. Roche is exploring additional studies in breast cancer and other tumour types with the hope of bringing the benefit of this targeted therapy to more people with PIK3CA mutations and addressing patient unmet needs.
