Roche Itovebi gets European Commission nod in fight against advanced breast cancer

“Itovebi is the first treatment of its kind to improve survival outcomes for those living with PIK3CA-mutated, ER-positive advanced breast cancer,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “Therefore, the Itovebi-based regimen may help address an important unmet need for people with this subtype of breast cancer.”

The approval is based on results from the phase III INAVO120 trial, published in the New England Journal of Medicine in October 2024, which showed a 57% reduction in the risk of disease worsening or death (progression-free survival [PFS]) with the Itovebi-based regimen compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43; 95% CI: 0.32-0.59, p<0.001) in the first-line setting. The PFS benefit was consistent across all pre-specified subgroups and the Itovebi-based regimen was well tolerated, with no new safety signals observed.

These results were reinforced by the INAVO120 final overall survival analysis that showed the Itovebi-based regimen reduced the risk of death by 33% (stratified HR=0.67; 95% CI: 0.48–0.94, p-value=0.0190 [boundary=0.0469]). Additionally, the treatment regimen substantially delayed the time to chemotherapy by approximately two years compared with palbociclib and fulvestrant alone (stratified HR=0.43; 95% CI: 0.30-0.60). These data were presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in the New England Journal of Medicine in May 2025.

Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations. The company is exploring additional studies in breast cancer and other tumour types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations.

Itovebi is an oral, targeted treatment that has been shown to provide well-tolerated and durable disease control in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer, who often have a poor prognosis and are in urgent need of new treatment options.

Itovebi has been designed to help minimise the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha, the company stated.

In addition to the European Commission’s approval, the Itovebi-based regimen is also approved for the treatment of adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer in the United States, Switzerland, Canada, Australia, United Arab Emirates, China and Taiwan, with data from INAVO120 under review with several other global health authorities.

ER-positive is a subtype of hormone receptor (HR)-positive breast cancer, the most prevalent type of all breast cancers, accounting for approximately 70% of cases. A defining feature of ER-positive breast cancer is that its tumour cells have receptors that attach to oestrogen, which can contribute to tumour growth.

People diagnosed with ER-positive and HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. The PI3K signalling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.