FDA Approves Roche's Itovebi for Advanced PIK3CA-Mutated Breast Cancer

Roche has announced that its drug, Itovebi™ (inavolisib), in combination with palbociclib and fulvestrant, has received approval from the United States Food and Drug Administration (FDA). This treatment is intended 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 mutation is found in about 40% of HR-positive metastatic breast cancers and is associated with poor prognosis.

The approval is based on the results from the Phase III INAVO120 study. This study demonstrated that the Itovebi-based regimen more than doubled progression-free survival compared to the regimen of palbociclib and fulvestrant alone in the first-line setting. Dr. Komal Jhaveri, one of the principal investigators of the study, emphasized the importance of the PI3K pathway in disease progression and mentioned that Itovebi's regimen significantly extended progression-free survival while maintaining a manageable safety profile.

Levi Garraway, Roche’s Chief Medical Officer, highlighted the significance of this approval, stating that it provides a crucial new first-line treatment option for people with HR-positive breast cancer with a PIK3CA mutation. Despite the high prevalence of PIK3CA mutations, treatment options have been limited until now, making this approval particularly meaningful.

The INAVO120 study included 325 patients and was a double-blind, placebo-controlled trial. Participants were randomly assigned to either the investigational or control treatment arm. The primary endpoint of the study was progression-free survival, while secondary endpoints included overall survival, objective response rate, and clinical benefit rate. The study found that the Itovebi regimen reduced the risk of disease worsening or death by 57% compared to the control group. Overall survival data were immature at the time of the primary analysis, but a positive trend was noted.

Jean Sachs, CEO of Living Beyond Breast Cancer, expressed excitement over the approval, calling it a significant advancement for patients with a PIK3CA mutation. She also emphasized the importance of early, comprehensive biomarker testing to help patients understand the most beneficial treatment options for their specific tumor type.

The Itovebi-based regimen was granted FDA Priority Review and Breakthrough Therapy Designation in May 2024, based on the INAVO120 study results. Data from this study are also being used for regulatory submissions to other global health authorities, including the European Medicines Agency. Itovebi is expected to become available in the US in the coming weeks. Comprehensive biomarker testing can help identify patients with HR-positive, HER2-negative breast cancer who have a PIK3CA mutation.

Roche is also investigating Itovebi in various combinations in two additional company-sponsored Phase III clinical studies (INAVO121 and INAVO122) for PIK3CA-mutated, locally advanced or metastatic breast cancer. These studies aim to explore further treatment combinations to address unmet needs in different cancer types.

HR-positive breast cancer is the most common subtype of breast cancer, accounting for around 70% of cases. This type of cancer is characterized by tumor cells that have receptors for oestrogen or progesterone, which can drive tumor growth. Patients with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, highlighting the need for additional treatment options.

Roche has been at the forefront of breast cancer research for over 30 years, aiming to develop innovative treatments for various subtypes of the disease. The company's efforts have led to significant advancements in treatment outcomes for human epidermal growth factor 2-positive and triple-negative breast cancers. Roche continues to explore new biomarkers and therapeutic approaches, especially for hormone receptor-positive breast cancer.